HUMAN PAPILLOMA VIRUS VACCINES / VACUNAS CONTRA EL VPH

Languages Ayuda

Bienvenido, Biblioteca Centro Medico Caracas

Iniciar sesión

Volver a los resultados de búsqueda

Contenidos

• 
  
• Interacciones de fármacos
• Calculadoras
• PCUs
• Novedades
• Información para el paciente

Find Patient Print Email

Recommendations for the use of human papillomavirus vaccines

Recommendations for the use of human papillomavirus vaccines

Authors
Philip E Castle, PhD, MPH
J Thomas Cox, MD
Joel M Palefsky, MD

Section Editor
Martin S Hirsch, MD

Deputy Editor
Allyson Bloom, MD

Disclosures: Philip E Castle, PhD, MPH Speaker’s Bureau: Roche Molecular Systems [cervical cancer (Cobas HPV test)]; Cepheid [cervical cancer (GeneXpert HPV test)]. Consultant/Advisory Boards: Roche [HPV testing (Cobas HPV test)]; Cepheid [cervical cancer (GeneXpert HPV test)]; Teva Pharmaceuticals [HPV therapeutics]; Genticel [HPV testing]; ClearPath [HPV testing]; Guided Therapeutics [HPV testing]; Hologic [HPV testing (Aptima HPV Test)]; GE Healthcare [Sample prep (FTA Elute-specimen transport medium)]. Data and Safety Monitoring Board: Merck [cervical cancer (Gardasil and Gardasil 9 HPV vaccines)]. J Thomas Cox, MD Speaker's Bureau: Roche [HPV testing (HPV test)]; Hologic/Gen-Probe [HPV testing (HPV test)]. Consultant/Advisory Boards: Merck [Data safety and monitoring board (Quadrivalent and nonavalent HPV vaccine)]; Roche [Advisory board (HPV test)]; Hologic/Gen-Probe [Advisory board (HPV test)]; Trovagene [Scientific advisory board (Urine HPV test)]; Zilico [Advisory board (Optical spectroscopy as a colposcopy adjunct)]. Joel M Palefsky, MD Grant/Research/Clinical Trial Support: Merck and Co [HPV infection (Quadrivalent and nonavalent HPV vaccines)]; Hologic [HPV infection (HPV assay)]. Consultant/Advisory Boards: Merck [HPV infection (Quadrivalent and nonavalent HPV vaccines)]; TheVax [HPV infection (therapeutic HPV vaccine)]; Antiva Biosciences [HPV infection (HPV therapeutics)]. Martin S Hirsch, MD Nothing to disclose. Allyson Bloom, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2015. | This topic last updated: Dec 10, 2015.

INTRODUCTION — Human papillomavirus is a sexually transmitted pathogen that causes anogenital disease in males and females. Persistent viral infection with high-risk human papillomavirus (HPV) genotypes causes virtually all cancers of the cervix. The same HPV genotypes (or "types") that cause cancer of the cervix also cause most cases of anal cancer [1] and significant proportion of oropharyngeal cancer in men and women, a significant proportion of vulvar and vaginal cancer, and significant proportion of penile cancer. Three vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil), one is 9-valent (Gardasil 9), and the other is a bivalent vaccine (Cervarix).

This topic will cover issues related to routine immunization recommendations, vaccination in special patient populations, and vaccine safety. The natural history, details on epidemiology, and immunology of HPV infection, as well as clinical trial data on HPV vaccines are discussed elsewhere. (See "Epidemiology of human papillomavirus infections" and "Clinical trials of human papillomavirus vaccines" and "The life cycle, natural history, and immunology of human papillomaviruses".)

DISEASE ASSOCIATIONS

HPV-related disease in females

Cervical cancer and precursor lesions — Cervical cancer is the third most common female cancer worldwide, with an estimated incidence of 530,000 and 270,000 related deaths in 2012; the attributable fraction due to HPV infection was estimated to be 100 percent [2,3]. HPV types 16 and 18 cause approximately 70 percent of cervical cancers and 50 percent of precancerous cervical lesions (ie, cervical intraepithelial neoplasia grade 2 and grade 3 [CIN2/3]). HPV types 31, 33, 45, 52, and 58 are estimated to cause an additional 19 percent of invasive cervical cancers [4]. The estimated annual incidence in the United States of CIN among females who undergo cervical cancer screening is 0.4 percent for CIN 1 and 0.5 percent for CIN 2/3 [5]. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis" and "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Incidence'.)

Vulvar and vaginal cancer and precursor lesions — Vulvar and vaginal cancer are rare cancers globally, with an estimated incidence of 27,000 vulvar cancers and 13,000 vaginal cancers in 2008; the attributable fraction due to HPV infection has been estimated to be 43 percent for vulvar cancer and 70 percent for vaginal cancer [2]. Other data have suggested that only 29 percent of vulvar cancers are HPV positive whereas 87 percent of vulvar intraepithelial neoplasia (VIN) are HPV positive [6]. HPV 16 and HPV 18 cause approximately 60 percent of HPV-positive vaginal cancers and precancerous vaginal lesions; HPV 16 and HPV 18 cause approximately 35 to 77 percent of HPV-positive vulvar cancers and 75 to 80 percent of precancerous vulvar lesions [6,7]. (See "Vaginal cancer" and "Vulvar intraepithelial neoplasia".)

HPV-related disease in females and males

Anal cancer and precursor lesions — Anal cancer is a rare cancer globally, with an estimated incidence of 27,000 in 2008 [2]. The attributable fraction of cases due to HPV is approximately 88 percent [2,8]. HPV types 16 and 18 cause approximately 70 to 85 percent of anal cancers and precancerous anal lesions (ie, anal intraepithelial neoplasia grade 2 and grade 3 [AIN2/3]) [1,8,9]. Although it remains an uncommon cancer, the incidence of anal cancer is increasing in the United States and other countries [10-12]. In data from the Surveillance, Epidemiology and End Results program of the National Cancer Institute, the annual incidence among males and females between 1994 and 2000 was approximately 2 per 100,000 [10]. The annual incidence of anal cancer among men who have sex with men (MSM) was estimated to be as high as 37 per 100,000 prior to the HIV epidemic [13], and the incidence of anal cancer among HIV-positive MSM is estimated to be approximately twice that of HIV-negative MSM [14,15]. (See "Classification and epidemiology of anal cancer", section on 'Epidemiology and risk factors'.)

Genital warts — HPV types 6 and 11 also cause 90 percent of genital warts. The incidence of HPV infection was evaluated in 8800 females who were enrolled in the placebo arms of two randomized trials of the HPV quadrivalent vaccine [16]. Three percent of the placebo recipients developed genital warts over approximately four years, the vast majority of which were associated with HPV 6 or HPV 11 infection. (See "Epidemiology of human papillomavirus infections", section on 'Genital warts'.)

Genital warts are associated with physical and psychological morbidity and have a high rate of treatment failure; furthermore, treatment of recurrent episodes is costly [17]. (See "Condylomata acuminata (anogenital warts) in adults".)

Oropharyngeal cancer — HPV infection may also play a role in the pathogenesis of squamous cell carcinomas of the head and neck. HPV-associated oral cancers are primarily found in the oropharynx and base of the tongue and tonsil [18-20]. HPV has also been linked to cancer of the larynx [21]. In the United States, the incidence of HPV-associated oropharyngeal cancers has been rising and the incidence of non-HPV-associated cancers has been declining, such that the incidence of the former now exceeds that of the latter [12,22]. (See "Human papillomavirus associated head and neck cancer".)

HPV-related diseases in males

Penile cancer and precursor lesions — Penile cancer is rare globally, with an estimated incidence of 22,000 cancers in 2008; the attributable fraction due to HPV was 50 percent [2]. HPV 16 and HPV 18 cause approximately 35 to 40 percent of penile cancers and 70-80 percent of HPV-positive penile cancers [23].

AVAILABLE VACCINES — Three different vaccines, which vary in the number of HPV types they contain, are available in the United States:

●Gardasil, a quadrivalent HPV vaccine, targets HPV types 6, 11, 16, and 18 [24].

●Gardasil 9, a 9-valent vaccine, targets the same HPV types as the quadrivalent vaccine (6, 11, 16, and 18) as well as types 31, 33, 45, 52, and 58 [25].

●Cervarix, a bivalent vaccine, targets HPV types 16 and 18 [26].

Dosing and administration is discussed elsewhere. (See 'Vaccine dose and administration' below.)
These are all prophylactic vaccines, designed to prevent HPV infection and subsequent HPV-associated lesions. Therapeutic vaccines, designed to induce regression of existing HPV-associated lesions, are in development but are not clinically available [27].

EFFICACY AND IMMUNOGENICITY IN FEMALES

Immunogenicity — Excellent antibody responses have been reported following immunization with both quadrivalent and bivalent vaccines [28-30]. Immunogenicity of the 9-valent vaccine among 9 to 26 year old females is comparable to that of the quadrivalent vaccine for the shared HPV types (6, 11, 16, and 18) [31,32].

Because efficacy studies were restricted to sexually active females, 15 years of age and older, immunological "bridging" studies have been conducted in females aged 9 to 15 years to demonstrate safety and immunogenicity. Following vaccination with the quadrivalent vaccine, the vaccine geometric mean titers (GMT) after 18 months in females aged 9 to 15 years were two- to threefold higher than in females aged 16 to 26 years for all targeted types [33]. Following vaccination with the 9-valent vaccine, the GMT in females aged 9 to 15 years were approximately twofold higher than in females aged 16 to 26 years for all targeted types [34,35]. Following vaccination with the bivalent vaccine, the GMT after seven months in females aged 10 to 14 years was noninferior to that observed in females aged 15 to 25 years, and in some studies, measured up to twofold higher [36-38].
In a head-to-head comparison of the immunogenicity of quadrivalent and bivalent HPV vaccines, immunization with the bivalent vaccine induced geometric mean titers of serum neutralizing antibodies 2.3- to 4.8-fold higher for HPV 16 and 6.8- to 9.1-fold higher for HPV 18 across all age strata compared with the quadrivalent vaccine [39]. Whether the induction of higher serum titers against HPV 16 and 18 has any impact on the degree and duration of protection is unknown. Furthermore, there is no defined minimum threshold titer for protection. Seroconversion from prior exposure has been shown to reduce the risk of incident HPV infection, suggesting that the titers resulting from natural infection, which are an order of magnitude lower than those elicited in vaccine studies, provide some level of protection [40,41].

Efficacy

Cervical, vaginal, and vulvar disease — Quadrivalent HPV vaccine [33,42], 9-valent HPV vaccine [31], and bivalent HPV vaccine [43] have been demonstrated in large clinical trials to prevent cervical disease, including cervical intraepithelial neoplasia (CIN2/3) and adenocarcinoma in situ. In these studies, HPV status was determined through serologic testing and DNA detection in cervical specimens, and vaccine effectiveness was greatest in females who did not have prior HPV infection. In addition, quadrivalent vaccine has also been demonstrated to reduce the incidence of genital warts and vaginal and vulvar intraepithelial neoplasia (VAIN and VIN 1-3).

●Quadrivalent HPV vaccine — Two large, randomized, double-blind, placebo-controlled trials have evaluated the efficacy of quadrivalent HPV vaccine in more than 17,000 adolescents and young females [33,42].

•Among HPV-naïve populations, the efficacy of quadrivalent HPV vaccine for preventing CIN2 or more severe disease due to HPV types included in the vaccine, was 97 to 100 percent.

•In the overall population of study participants (with or without prior HPV infection), the efficacy of quadrivalent HPV vaccine for preventing CIN2, or more severe disease due to HPV types included in the vaccine was significantly lower at approximately 44 percent after a mean follow-up period of three years. This reduction in efficacy reflects the fact that the vast majority of enrollees in this trial were already sexually active and many had been previously infected with vaccine HPV types. (See 'Timing of immunization' below.)

Data collected outside the clinical trial setting are also favorable, demonstrating decreased prevalence of HPV-related cervical disease and genital warts following introduction of quadrivalent vaccine into national immunization programs. (See "Epidemiology of human papillomavirus infections", section on 'Effect of HPV vaccine'.)

●9-valent vaccine — An international trial reported the efficacy of the 9-valent vaccine in approximately 14,000 females aged 16 to 26 years who were randomly assigned to receive the quadrivalent or 9-valent vaccine [31].

•Among HPV-naïve populations, the efficacy of 9-valent vaccine for preventing CIN2 or more severe disease, VIN2 or 3, and VaIN2 or 3 associated with HPV types 31, 33, 45, 52, and 58 was 97 percent.

•In the overall population of study participants (with and without prior HPV infection), the rates of high-grade cervical, vaginal, and vulvar disease were the same among women who received the 9-valent vaccine and those who received the quadrivalent vaccine (14 cases/1000 person years in both groups).

●Bivalent HPV vaccine — One large randomized clinical trial in more than 18,000 young females aged 15 to 25 years demonstrated the efficacy of bivalent HPV vaccine [43].

•Among HPV-naïve patients, the efficacy of the bivalent vaccine for preventing CIN2 or more severe disease due to HPV types included in the vaccine was 93 percent, comparable with the efficacy of the HPV quadrivalent vaccine.

•In the overall population of study participants (with and without prior HPV infection), vaccine efficacy for preventing CIN2 or more severe disease due to HPV types included in the vaccine was significantly lower at 53 percent after a mean follow-up period of approximately three years. These data are consistent with those seen with HPV quadrivalent vaccine and emphasize the need to vaccinate individuals before the onset of sexual activity to gain the greatest benefit and maximize cost effectiveness. (See 'Timing of immunization' below.)

HPV vaccination appears to be safe and effective in preventing subsequent infection in older women, but the overall benefit is less than that in younger females [44]. In a trial of 5752 women older than 25 years who were randomly assigned to receive bivalent vaccine or placebo and followed for a mean of 40 months, vaccine efficacy for the combined endpoint (preventing six-month persistent cervical HPV type 16 or 18 infection or vaccine-type associated CIN grade 1 or more severe diagnoses) was 44 percent overall [45]. Among those who did not have a prior history of HPV infection and received all three doses of vaccine, vaccine efficacy was 81 percent. Rates of vaccine-type associated CIN2 or more severe diagnoses were not statistically different between HPV-naïve women who received vaccine or placebo.

Anal disease — There are no direct efficacy data regarding the prevention of anal intraepithelial neoplasia (AIN) and anal cancer in females specifically; however, since the majority of anal cancers in females are related to HPV 16 and HPV 18, a beneficial impact of vaccination to prevent anal intraepithelial neoplasia and anal cancer in females is anticipated. Additionally, in a study of women who had participated in a trial of the bivalent vaccine, vaccine efficacy against prevalently detected anal HPV types 16 and 18 infection was 84 percent, similar to the efficacy against cervical infection with these types [46]. Prevention of AIN and anal cancer is an indication for vaccination in females with the quadrivalent vaccine. (See 'Recommendations for HPV immunization in females' below.)

Oral disease — Bivalent HPV vaccination has also been associated with reduction in the prevalence of oral infection with HPV types 16 and 18. In a trial originally designed to evaluate the vaccine efficacy against cervical HPV disease among 7466 females in Costa Rica, fewer participants who were randomly assigned to receive bivalent HPV vaccination (1 of 2910) had detectable HPV types 16 or 18 on an oral specimen four years after vaccination compared with those who received the control hepatitis A vaccination (15 of 2924) [47]. Vaccine efficacy for the prevention of oral HPV was estimated to be 93 percent. Whether HPV vaccination can prevent the development of HPV-related oropharyngeal cancer has not yet been evaluated.

RECOMMENDATIONS FOR HPV IMMUNIZATION IN FEMALES

Indications and choice of vaccine — Various guideline committees have made recommendations regarding the use of HPV vaccine, which are discussed below. We are in general agreement with the recommendations from the United States Advisory Committee on Immunization Practices (ACIP). (See 'Advisory Committee on Immunization Practices' below.)

While all guidelines target the same age group for routine vaccination, they differ in the catch-up age range. This is primarily due to cost-effectiveness analyses which show the benefit and cost effectiveness is lower when vaccination is given at older ages. (See 'Cost effectiveness' below.)

Advisory Committee on Immunization Practices — The United States Advisory Committee on Immunization Practices (ACIP) recommends the bivalent, quadrivalent, or 9-valent HPV vaccine for females aged 11 to 12 for the prevention of cervical, vaginal, and vulvar cancer and the related precursor lesions caused by the HPV types targeted by these vaccines [48-50]. The ACIP also recommends the quadrivalent or 9-valent HPV vaccine for the prevention of anal cancer and its precursor lesions, and genital warts in females.

These vaccines can be administered to females as young as age nine. Catch-up vaccination is also recommended for females aged 13 to 26 years who have not been previously vaccinated or who have not completed their vaccine series.
We recommend the 9-valent vaccine given its greater HPV type coverage than the other HPV vaccines. Re-vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.

Pediatric, gynecologic, and family practice societies — Recommendations from the American Academy of Pediatrics (AAP), the American Academy of Family Practice (AAFP), and the American College of Obstetricians and Gynecologists (ACOG) are all largely consistent with the ACIP guidelines above.

American Cancer Society — Similar to the ACIP, the American Cancer Society (ACS) guidelines recommend that HPV vaccination should be routinely offered to females aged 11 to 12 years; immunization may begin at nine years of age [51]. However, the ACS recommends catch-up vaccination for females aged 13 to 18 who have not been previously vaccinated or completed their vaccine series. The ACS notes that there is insufficient evidence to recommend for or against vaccination of females aged 19 to 26 years.

World Health Organization — The World Health Organization (WHO) position paper suggests that girls within the age range of 9 through 13 years should be the primary target population for HPV immunization (www.who.int/wer). It notes that local public health programs should recommend vaccination of older females only if it is affordable and cost effective and does not divert resources from vaccinating the primary target population or screening for cervical cancer.

Timing of immunization — Clinical trial data of vaccine efficacy in males and females suggest that immunization with HPV vaccine is most effective among individuals who have not been infected with HPV (eg, patients who are "HPV-naïve"). Thus, the optimal time for HPV immunization is prior to an individual’s sexual debut. Neither vaccine treats or accelerates the clearance of pre-existing vaccine-type HPV infections or related disease.

Females who are sexually active should still be vaccinated consistent with age-specific recommendations. A history of an abnormal Papanicolaou test, genital warts, or HPV infection is NOT a contraindication to HPV immunization [49]. However, immunization is less beneficial for females who have already been infected with one of more of the HPV vaccine types.

EFFICACY AND IMMUNOGENICITY IN MALES — Interest in HPV vaccine efficacy and safety in young males has not only included prevention of HPV-related diseases (genital warts, anal cancer, and penile cancer), but also possible decreased transmission of HPV infection to female sex partners and potential for prevention of oral cancers associated with HPV 16 and 18 [20].

Immunogenicity — Studies with quadrivalent HPV vaccine, 9-valent HPV vaccine, and bivalent HPV vaccine have demonstrated that the proportions of vaccine recipients who achieve seroconversion is comparable in males (eg, 99 to 100 percent) and females (eg, 93 to 100 percent) [34,52,53]. Eighteen months following vaccination with the quadrivalent vaccine, the geometric mean titers (GMTs) against all four targeted types in males aged 9 to 15 years were noninferior to those in females of the same age [53]. Following vaccination with the 9-valent vaccine, the GMTs against all included HPV types in males aged 9 to 15 and aged 16 to 26 years were similar to those in females aged 16 to 26 years [34,35]. Following vaccination with bivalent vaccine, the GMTs against both targeted types in males aged 10 to 18 years and 10 to 14 years were higher than those historically reported for females aged 15 to 25 years and 10 to 14 years, respectively [52]. As in females, there is no defined minimum threshold titer for protection in males. (See 'Immunogenicity' above.)

Efficacy — In a placebo-controlled international trial, the efficacy of quadrivalent HPV vaccine was evaluated among 4065 males aged 16 to 26 [54]. The following results were demonstrated:

●The efficacy of immunization against the development of external genital lesions and persistence of HPV infection (by HPV 6, 11, 16, or 18 types) was 90 percent and 86 percent, respectively, among HPV-naïve males (no evidence of infection with the relevant HPV vaccine types at enrollment) who received all three doses of vaccine.

●In contrast, vaccine efficacy was significantly lower among the overall patient population with or without HPV infection at enrollment (66 percent for the prevention of external genital warts and 48 percent for the prevention of persistent HPV infection).

●The efficacy of HPV immunization in preventing anal intraepithelial neoplasia secondary to the relevant HPV vaccine types was assessed in a planned sub-study of 602 men who have sex with men (MSM). Similar to the above results, vaccine efficacy was higher in the HPV-naïve compared with the overall MSM population (78 versus 50 percent, respectively).

RECOMMENDATIONS FOR HPV IMMUNIZATION IN MALES

Indications and choice of vaccine — The Advisory Committee on Immunization Practices (ACIP) recommends the routine use of quadrivalent or 9-valent HPV vaccine in males aged 11 or 12 years [48-50]. The vaccination series can be administered to individuals as young as nine years. Vaccination is also recommended for males aged 13 to 21 years who have not been vaccinated previously or who have not completed the three-dose series. For males who have sex with males (MSM) and for males who are immunocompromised (including HIV infection), ACIP recommends vaccination through age 26 for those not previously vaccinated.

For other males, the ACIP supports "permissive use" of HPV vaccination in males aged 22 through 26 years. Permissive use means that the vaccine is recommended, but not considered to be of sufficient priority to include on routine vaccination schedules. Vaccines recommended on a permissive basis are less likely to be covered by a patient’s health insurance company.
We recommend the 9-valent vaccine over the quadrivalent vaccine for males given its greater HPV type coverage. Although it is not clear that greater HPV type coverage would substantially improve male cancer prevention, it would likely further reduce the risk of cervical cancer in women indirectly through herd immunity. Repeat vaccination with the 9-valent vaccine is likely not warranted for individuals who have completed a series with a different HPV vaccine.
The decision of the ACIP panel to recommend HPV vaccination among males was based on: a) vaccine efficacy data on genital warts and persistent HPV infection and prevention of anal intraepithelial neoplasia in MSM [54,55] and b) vaccine safety data [56]. Cost-effectiveness analyses have suggested that male vaccination is less cost effective than female vaccination [57,58]. However, the overall cost effectiveness of male vaccination depends on a range of assumptions, such as vaccine efficacy, vaccine coverage of females, the range of health outcomes included, and the effect of HPV-associated diseases on quality of life [49]. Male vaccination may be more cost effective with low vaccination coverage among females, which is the current situation in the United States [59].

Timing of immunization — Clinical trial data of vaccine efficacy in males and females suggest that immunization with HPV vaccine is most effective among individuals who have not been infected with HPV (eg, patients who are "HPV-naïve"). Thus, the optimal time for HPV immunization is prior to an individual’s sexual debut. Neither vaccine treats or accelerates the clearance of pre-existing vaccine-type HPV infections or related disease.

Males who are sexually active may still be vaccinated consistent with age-specific recommendations. A history of anal intraepithelial neoplasia, genital warts, or HPV infection is NOT a contraindication to HPV immunization [49]. However, immunization is less beneficial for males who have already been infected with one or more of the HPV vaccine types.

Controversies — Opponents of HPV immunization in males argue that [60]:

●The burden of HPV-associated diseases such as anal, penile, and oropharyngeal cancers in males is less than that of cervical cancer in females [61].

●Public health initiatives should be most focused on attaining high rates of immunization in young girls as it is the most cost effective.

Proponents of HPV immunization in males argue that:

●Immunization rates in young girls have been generally low, particularly when immunizations are not mandatory [62]. It is under these conditions that both incremental benefit and cost effectiveness of vaccinating males have been shown [63].

●High coverage programs in females confer protection against HPV-related infection and disease in heterosexual males, but not MSM.

●HPV infection is common in males and is readily transmitted, influencing disease infection rates in both males and females [64,65].

One modeling study highlighted the incomplete protection of men from HPV-associated disease if only females are vaccinated [63]. Using population data from the Netherlands, it estimated that the burden of HPV-associated cancers in men would be reduced by 37 and 66 percent if vaccine uptake among girls and young women were 60 and 90 percent, respectively. Vaccine uptake among females is considerably less than 60 percent in many locations. (See 'Strategies to improve vaccine coverage' below.)

IMMUNIZATION IN SPECIAL PATIENT POPULATIONS

Pregnant females — Although none of the approved HPV vaccines contain live virus, use in pregnancy is not recommended because of limited data on safety [49]. Lactating females can receive the immunization series since subunit vaccines do not affect the safety of infant breastfeeding. (See "Immunizations during pregnancy".)

If a woman receives the HPV vaccine before she knows that she is pregnant she should be reassured that there is no evidence that this vaccine will harm the pregnancy. This is discussed in detail elsewhere. (See "Immunizations during pregnancy", section on 'Human papillomavirus'.)
Females who have started the series, but become pregnant before completion of all three shots, may resume the series when postpartum. (See "Immunizations during pregnancy".)
Both vaccine manufacturers maintain pregnancy registries to monitor fetal outcomes of pregnant females exposed to HPV vaccine [49]. In the United States, exposures to the quadrivalent vaccine can be reported by calling 877-888-4231, and exposures to the bivalent vaccine can be reported by calling 888-452-9622.

Immunization in females with pre-existing cervical abnormalities or genital warts — A history of genital warts, abnormal cytology, or positive HPV DNA test result is not evidence of prior infection with any or all of the vaccine HPV types, and vaccination can still provide protection against infection with HPV vaccine types not already acquired. Thus, the Advisory Committee on Immunization Practices (ACIP) recommends immunization for females (up to 26 years of age) with any such history [48,49]. Additionally, the ACIP recommends against assessment with Pap testing or screening for existing HPV infection as part of the determination for HPV vaccine candidacy.

However, these patients should be advised that vaccination will have no therapeutic effect on pre-existing HPV infection or cervical intraepithelial neoplasia, and the potential benefit of HPV vaccination is not as great as if they were vaccinated before they started having sex.

Immunosuppressed or immunocompromised hosts — Transplant recipients and HIV-infected patients, particularly those with low CD4 counts (<200 cells/mm³) are at risk for HPV-related disease. (See "HIV and women", section on 'Abnormal cervical cytology'.)

Studies of the HPV quadrivalent vaccine in HIV-infected adult men [66], HIV-infected women aged 16 to 23 years [67,68], and HIV-infected boys and girls aged 7 to 12 years [69] suggest that it is both immunogenic and safe in these populations. However, efficacy data are not yet available. Studies in other immunocompromised populations are ongoing.
HPV vaccine is recommended by the ACIP for persons who are immunocompromised as a result of infection, disease, or medications through age 26 years if they have not already received any or all vaccine doses [48,49]. It is not a live vaccine. HPV vaccination in transplant recipients is discussed elsewhere. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Human papillomavirus' and "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Human papillomavirus'.)
Cervical cancer screening continues to play an important role in detection and treatment of cervical intraepithelial neoplasia (CIN) 2, 3, and cervical cancer in these high-risk females. Although there are no formal guidelines regarding screening for precancerous anal lesions, some specialists recommend anal cytologic screening for HIV-1-infected males and females. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention" and "HIV and women" and "Immunizations in HIV-infected patients" and "Anal squamous intraepithelial lesions: Diagnosis, screening, prevention, and treatment", section on 'Screening for anal SIL'.)

Healthcare workers — The Advisory Committee on Immunization Practices (ACIP) immunization schedule of 2012 indicates that healthcare personnel are not at increased risk of HPV infection due to occupational exposure; age-based recommendations noted above still apply [70].

PREVACCINATION ASSESSMENT — The ACIP does not recommend serologic or HPV DNA testing prior to immunization in females or males [49].

VACCINE DOSE AND ADMINISTRATION

Immunization schedule — In the United States, the HPV vaccine series is three vaccine doses given over a minimum of 24 weeks [49]. The minimum interval between the first two doses is four weeks and the minimum interval between the second and third doses is 12 weeks. The quadrivalent vaccine (Gardasil) and 9-valent vaccine (Gardasil 9) are typically administered in three doses at time zero, and at two and six months of follow-up. The bivalent vaccine (Cervarix) is typically administered in three doses at time zero, and at one and six months of follow-up. HPV vaccine can be safely administered at the same time as other age-appropriate vaccines at a different anatomic site.

In general, the same formulation should be used to complete the series, if possible. However, if the HPV vaccine formulation initially used is unknown or unavailable, or if the 9-valent vaccine is being introduced into the formulary, a different HPV vaccine formulation can be used to complete the series [50].
In some countries, two doses of HPV vaccine are recommended because of evidence of generally comparable immunogenicity and, for some outcomes, efficacy after two versus three doses. This evidence is discussed in detail elsewhere (see 'Missed doses/alternative schedules' below). As an example, the Strategic Advisory Group of Experts on Immunizations (SAGE) of the World Health Organization recommends two doses for females under the age of 15 and three doses for those who initiate vaccination later [71]. Practitioners outside the United States should consult local guidelines for the recommended immunization schedule in their country.
Administering HPV vaccine at the same time as certain other vaccines (ie, tetanus, acellular pertussis, and diphtheria vaccine and inactivated poliovirus vaccine) does not appear to adversely affect the immune response to either the HPV vaccine or the concomitant vaccine [72,73].

Missed doses/alternative schedules — Patients often do not follow up for their immunizations on schedule [74]. The Advisory Committee on Immunization Practices (ACIP) recommends that if the vaccination series is interrupted for any length of time, it can be resumed without restarting the series.

Because of the frequency of missed doses and the suboptimal adherence to a three dose vaccine schedule, there has been interest in whether fewer doses or greater time intervals between doses remain effective. Randomized trials are planned to evaluate this issue. Some observational data suggest that administration of two vaccine doses has comparable efficacy against vaccine type HPV infection and, for the quadrivalent vaccine, the incidence of genital warts, and is comparably immunogenic as three doses, but there have been no studies evaluating the efficacy of fewer than three doses on prevention of cervical neoplastic disease. In some countries (not the United States), the recommended vaccine series for certain individuals consists of two doses. A single vaccine dose is not a recommended option. (See 'Immunization schedule' above.) In an analysis of data from two trials of the bivalent HPV vaccine in young women (aged 15 to 25 years) who had no HPV type 16 or 18 infection at baseline and who had at least 12 months of follow-up, vaccine efficacy against six-month persistent infection with those HPV types was no different in women who received the intended three doses compared with those who received fewer doses (89, 90, and 97 percent efficacy with three, two, and one vaccine doses, respectively) [75]. For women who received only two doses, vaccine efficacy was generally similar among those who received the second dose one or six months after the first. However, cross-protective efficacy against non-vaccine types with two doses given one month apart was inferior to both three doses and two doses given six months apart.
Similarly, one observational study suggested that two quadrivalent vaccine doses provided substantial protection against genital warts, although completion of three doses was slightly superior [76]. In the study, over one million Swedish females aged 10 to 24 years who did not have a history of genital warts or HPV vaccination at study entry were followed for a mean of 3.8 years. Receipt of three doses of vaccines was associated with the lowest subsequent incidence of genital warts (128 versus 528 events per 100,000 person years without vaccination), but receipt of two doses and one dose were also associated with a substantially lower incidence (174 events and 384 per 100,000 person years, respectively). Among females who were aged 10 to 16 years when first vaccinated, after adjusting for parental education and age, three doses of the vaccine were associated with 59 fewer events per 100,000 person-years (95% CI 2-117) than two doses and 75 fewer events per 100,000 person years (95% CI -7-157) than one dose. In a similar study from Denmark, three quadrivalent vaccine doses were also associated with an overall lower risk of genital warts than two doses, but when the two vaccine doses were administered at least six months apart, the reduction in risk for genital warts appeared comparable to that with three doses [77].
Other studies have examined the effects of varied dosing schedules on immunogenicity, as an indirect measure of potential efficacy. In an analysis of a Costa Rican trial of bivalent HPV vaccination, seropositivity against HPV types 16 and 18 four years after vaccination was 100 percent among those who had only received one dose (n = 78), two doses separated by one month (n = 140), or two doses separated by six months (n = 52) [78]. Antibody levels were comparable between those who received two doses separated by six months and a random selection of women who received all three doses as intended. A clinical trial in Vietnam, which evaluated three alternative schedules with longer intervals between vaccine doses compared with standard dosing among 809 girls (aged 11 to 13 years), found equivalent HPV antibody titers one month after the final dose [79]. A follow-up analysis suggested that antibody titers were comparable across dosing schedules after two and a half years [80]. A randomized trial to evaluate the immune response to two doses (at zero and six months) versus standard three doses (at zero, two and six months) found that the antibody responses following two doses was noninferior to three doses for all four HPV types at seven months but inferior for HPV18 and HPV6 at 36 months [81].

Postvaccination serology — There is no evidence that the measurement of postvaccination antibody titers to monitor immunity is useful for determining who is protected against infection by the vaccine-targeted types.

Duration of protection — HPV vaccines have shown excellent duration of protection for the time periods through which they have been studied. Continued protection against high grade cervical, vaginal, and vulvar neoplasia has been observed through 42 months following vaccination among female trial participants [82]. Persistent antibody levels and protection against HPV infection have been reported up to 10 years following vaccination [83-85]. Of note, the precise level of antibody needed for protection against infection is unknown. Further data will become available in the future as female and male participants in vaccine studies are followed over time.

VACCINE SAFETY — All vaccines use virus-like particles (VLPs), which mimic the viral capsid. VLPs do not contain genetic material and are produced in biologic systems, which have well-established safety records [86].

All vaccines appear to be safe in the context of clinical trials, although more is known about the safety profile of the quadrivalent vaccine than the 9-valent or bivalent vaccines due to availability of more postlicensure data, which are summarized below [87].

Quadrivalent vaccine (Gardasil) — Vaccine safety data are now available from both registration trials and in postlicensure safety surveillance systems. Different types of information can be gleaned from these two processes. The advantage of safety reviews within the context of a clinical trial is that medical chart reviews of adverse events are usually more thorough and complete, whereas surveillance systems are voluntary and passive. However, postlicensure surveillance systems have the advantage of identifying a potentially serious side effect that may have been too rare to detect during prelicensure trials.

The postlicensure safety profile is broadly consistent with safety data from prelicensure trials that suggest the vaccine is safe and well tolerated apart from mild injection site reactions, although syncopal events have emerged as a potential serious adverse effect [88]. The incidence of syncope among adolescents has increased overall with the introduction of other routine immunizations as well, such as meningococcal vaccine [88,89]. The ACIP recommends a routine 15-minute waiting period following vaccination so that the patient may continue in a sitting or supine position as needed; this may decrease the risk of syncope with subsequent injury.
In light of the growing data on the safety of the HPV vaccine, the World Health Organization’s Global Advisory Committee on Vaccine Safety stated that the benefit-risk profile remains favorable [90]. Additionally, it notes concern about claims of harm raised on the basis of anecdotal reports in the absence of biological or epidemiological substantiation.

Prelicensure trial data — The safety profile of the quadrivalent vaccine was evaluated in diverse populations of females from resource-rich and resource-limited settings [33,42]. Mild injection site reactions were the most commonly observed adverse events [91,92]. The safety profile of quadrivalent vaccine in males was reported to be similar to that of studies in females [54].

Postlicensure data — In the United States, adverse events following immunization are collected and analyzed within the Vaccine Adverse Event Reporting System (VAERS) [88,93,94]. Adverse events following HPV vaccine are compared with background rates following other immunizations. Between June 2006 and March 2013, approximately 57 million doses of quadrivalent HPV vaccines were distributed in the United States. Reports of adverse events to VAERS have been consistent with the pre-licensure data:

●From 2006 to 2013, VAERS received 21,194 reports of adverse events following HPV immunization among females [94]. The vast majority (92 percent) were considered mild. The proportion of events reported as serious peaked in 2008. Among serious events, headache, nausea, vomiting, fatigue, dizziness, syncope, and generalized weakness were the most frequently reported. There is no increased risk of Guillain-Barré Syndrome compared with other vaccines in similar age groups [88].

●Through 2011, 72 post-vaccination deaths had been reported, of which 34 were confirmed. There was no unusual pattern or clustering to the deaths that would suggest that they were caused by the vaccine [93].

Other studies have similarly observed that the quadrivalent vaccine is generally safe [56,95,96].
There does appear to be an increased risk of syncope with the quadrivalent vaccine, but whether this is unique to this vaccine is unclear. A disproportionate number of syncopal events following quadrivalent vaccine administration had been reported to the VAERS [88]. Among the 1896 syncopal events reported, 15 percent resulted in a fall or injury. Similarly, in an industry-sponsored study of almost 190,000 females in a large healthcare system who received at least one vaccine dose, emergency department visits or hospitalizations were higher during the post-vaccine period compared with a subsequent control period for 10 of 265 diagnostic categories evaluated, including viral, bacterial, and skin infections and congenital anomalies [95]. An independent safety committee concluded that same-day syncopal events (OR 6.0, 95% CI 3.9-9.2) and local skin infections within two weeks of vaccination (OR 1.8, 95% CI 1.3-2.4) were the only adverse events likely associated with vaccine administration.
Other adverse events that appeared to be vaccine-related have not been substantiated by further study. Although venous thromboembolism (VTE) rates reported to the VAERS were higher for quadrivalent vaccine than other vaccines, of the 31 patients with thromboembolism reported through 2008, 28 (90 percent) had a known risk factor (ie, estrogen-containing birth control pills or a family history of clotting disorder) [88]. In a study of adverse events following over 600,000 quadrivalent vaccine doses administered to females in seven large managed care organizations, there was a nonsignificant increase in the risk of VTE following vaccination among females aged 9 to 17 years, but individual review of the eight potential VTE cases indicated that only five met the standard case definition and all had other known risk factors for VTE (eg, oral contraceptive use, coagulation disorders, smoking, obesity, or prolonged hospitalization) [56]. Additionally, in a study of 1.6 million Danish women, of whom 30 percent had received quadrivalent HPV vaccine, there were over 4000 cases of incident VTE, but there was no association between vaccine receipt and VTE [97].
Anaphylaxis had also been reported following administration of the quadrivalent vaccine [88,98], although this risk has not been confirmed in other studies. In a mass school-based national vaccination program in Australia, the incidence of anaphylaxis was 2.6 per 100,000 doses [98]. However, some of those cases were subsequently thought not to have represented anaphylaxis and other studies from Australia did not confirm this high rate [99,100]. In the VAERS surveillance system, only 10 cases met predefined criteria for anaphylaxis; the overall risk ratio was 0.1 case per 100,000 doses distributed [88]. (See "Allergic reactions to vaccines".)
Although anecdotal and sporadic case reports had raised concerns about a potential causal relationship between HPV vaccination and development of multiple sclerosis and other demyelinating disorders, larger studies have refuted this. In a study of nearly four million Swedish and Danish females aged 10 to 44 years, receipt of quadrivalent vaccination was not associated with demyelinating diseases, including multiple sclerosis, optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis, as documented by billing codes [101].

9-valent vaccine (Gardasil 9) — In a trial in which over 7000 females received the 9-valent vaccine, the main reported adverse effects were mild or moderate injection site reactions (pain, erythema, and swelling). These occurred slightly more frequently than with the quadrivalent vaccine [34]. The frequency of systemic adverse effects (eg, headache, fever, nausea, dizziness) was similar with the 9-valent and quadrivalent vaccines.

Bivalent vaccine (Cervarix) — In a phase III, multinational prospective, double-blind, placebo-controlled trial of more than 18,000 females aged 15 to 25 years, the vaccine was well tolerated and there were no differences in serious adverse events between vaccine and placebo recipients. Because of low uptake of Cervarix in the US as of September 2011, only sparse postlicensure data are available. As of September 2011, there have been 52 VAERS reports of adverse events following administration of bivalent vaccine and the majority of these adverse events (98 percent) were considered nonserious.

Behavioral impact — Some surveys of parents found a concern for sexual disinhibition in adolescent girls following HPV vaccine receipt, particularly among older and ethnic minority parents [102,103]. Studies have not supported an increase in risky sexual behavior following vaccination [104-106]. In a retrospective study of preteenage girls enrolled in a large healthcare system, the combined incidence of pregnancy testing, chlamydia testing, and contraception counseling was determined among those girls who did (n = 493) and did not (n = 905) receive at least one HPV vaccine dose [104]. After adjustment for baseline healthcare utilization, race, and socioeconomic status, HPV vaccination was not associated with an increased rate of these sexual activity-related outcomes.

WHERE TO REPORT ADVERSE EVENTS — Additional data on the Vaccine Adverse Event Reporting System are available on the web [93]. Instructions for reporting adverse events to the Vaccine Adverse Event Reporting System are available at www.vaers.hhs.gov or by calling 800-822-7967 in the United States.

STRATEGIES TO IMPROVE VACCINE COVERAGE — Some countries, such as Australia, the United Kingdom, and Denmark, have achieved relatively high full-dose uptake of HPV vaccination (> 60 percent) through inclusion of the vaccine in national vaccination programs [107-109]. In the United States, uptake of HPV vaccination has been suboptimal. In 2012, based on results of a national survey among adolescents who had provider-reported vaccination records, estimated vaccine coverage among females aged 13 to 17 was 54 percent for at least one dose and only 33 percent for three doses [94]. In the survey, parents who did not intend to have their daughters vaccinated gave the following as their top five reasons: the vaccine was not needed, the vaccine was not recommended, concern about vaccine safety, lack of knowledge about the vaccine or disease, and lack of sexual activity by their daughter. This highlights a lack of understanding about the rationale for HPV vaccination on the part of the parent and the important role of the healthcare provider in consistently and clearly educating parents about vaccination.

Lack of opportunity did not appear to be a major reason for low vaccine coverage. Of the unvaccinated females in the survey, 84 percent had at least one medical visit at which they were given a different vaccine but not the HPV vaccine [94]. Vaccination rates may be particularly low among certain demographic subgroups. As an example, in a survey of 3253 females aged 15 to 25 years, only 29 percent reported initiating HPV vaccination despite 84 percent being aware of it [110]. Among self-described lesbians, only 9 percent of those aware of HPV vaccination had received it.
The implications of these findings are significant. Some experts estimate that by increasing three-dose HPV vaccination coverage to 80 percent in females, approximately 53,000 additional cases of cervical cancer could be prevented in the US over the lifetimes of those currently aged ≤12 years [58,94].
Attempted community- or practice-based interventions to improve uptake of HPV vaccine include patient reminders, physician-focused interventions (auditing and feedback or alerts to remind physicians to offer vaccination), school-based vaccination programs, and social marketing strategies. In a systematic review of studies evaluating the efficacy of such interventions, most suggested an improvement in at least one HPV vaccination outcome (eg, initiation or completion of greater number of doses) with these strategies [111].

IMPORTANCE OF CANCER SCREENING

Cervical screening — Cervical cancer screening with cervical cytology (ie, Papanicolaou test) has reduced the incidence and mortality of cervical cancer by more than 70 percent over the past six decades [112]. Screening for cervical cancer by cervical cytology and/or HPV testing is recommended for all females beginning at age 21 [113]. A preventive healthcare visit is an opportune time to discuss and offer HPV vaccination and/or cervical screening depending on the age of the woman [51]. Detailed information regarding screening for cervical cancer is found elsewhere. (See "Screening for cervical cancer".)

Cervical cancer screening continues to be of great importance since immunization with the bivalent or quadrivalent HPV vaccine will not prevent approximately 25 to 30 percent of cervical cancers in HPV-naïve females and does not protect females already infected with carcinogenic HPV types against the development of cancer. The optimal approach to cervical cancer screening in HPV-naïve females who have received the 9-valent vaccine and are thus protected against 90 percent of cervical cancer is unclear, but until further data are available, screening should continue for all vaccinated females.

Anal screening — Although there are no formal guidelines regarding screening for precancerous anal lesions, some specialists recommend anal cytologic screening for HIV-1-infected males and females. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention" and "HIV and women" and "Immunizations in HIV-infected patients" and "Anal squamous intraepithelial lesions: Diagnosis, screening, prevention, and treatment", section on 'Screening for anal SIL'.)

COST EFFECTIVENESS — Mathematical models have examined the cost effectiveness of HPV vaccination [114-117]. One study suggested that vaccination of the entire United States population of 12-year-old girls would annually prevent more than 200,000 HPV infections, 100,000 abnormal cervical cytology examinations, and 3300 cases of cervical cancer if cervical cancer screening continued as currently recommended [114].

Vaccination becomes increasingly less cost effective with increasing age. Assuming that HPV vaccine provides lifelong immunity, the cost-effectiveness ratio is $43,600 per quality-adjusted life-year (QALY) gained when vaccinating 12-year-old girls [118]. However, in one analysis the cost of extending immunizations up to the age of 26 years was $152,700 per QALY [118]. As in all cost-effectiveness studies, interpretation of these findings is limited by uncertainty and multiple assumptions made in the models.
In various models, vaccinating both males and females is predicted to be more beneficial in reducing HPV infection and disease than by vaccinating only females, but at a higher cost than vaccinating females alone [118-120]. However, models of cost effectiveness are limited by uncertainty regarding major issues such as duration of protection [121], the effect of herd immunity, level of vaccine uptake among girls and females, and the prevalence of vaccine-specific HPV types circulating in age-specific populations [122]. (See "Epidemiology of human papillomavirus infections".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient information: Human papillomavirus (HPV) vaccine (The Basics)" and "Patient information: Anogenital warts (The Basics)" and "Patient information: Pap tests (The Basics)" and "Patient information: Vaccines for children age 7 to 18 years (The Basics)")

●Beyond the Basics topics (see "Patient information: Human papillomavirus (HPV) vaccine (Beyond the Basics)" and "Patient information: Genital warts in women (Beyond the Basics)" and "Patient information: Cervical cancer screening (Beyond the Basics)" and "Patient information: Vaccines for children age 7 to 18 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Persistent viral infection with carcinogenic HPV types causes virtually all cancer of the cervix and most cases of anal cancer. The carcinogenic types, HPV 16 and HPV 18, which are targeted by the current HPV vaccines, cause approximately 70 percent of all cervical cancers worldwide and 72 percent of anal cancers. HPV types 31, 33, 45, 52, and 58 are estimated to cause an additional 19 percent of invasive cervical cancers. HPV 6 and HPV 11 cause approximately 90 percent of genital warts. (See 'Disease associations' above.)

●The quadrivalent vaccine (Gardasil) includes HPV types 6, 11, 16, and 18. The 9-valent vaccine (Gardasil 9) includes HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The bivalent vaccine (Cervarix) includes HPV types 16 and 18. (See 'Available vaccines' above.)

●HPV immunization is most effective among individuals who have not yet been infected with HPV (eg, before sexual debut). (See 'Timing of immunization' above.)

●Multicenter, double-blind, placebo-controlled trials have demonstrated efficacy of quadrivalent, 9-valent, and bivalent HPV vaccines against incident and persistent cervical HPV infection due to vaccine types and the development of cervical intraepithelial neoplasia. Quadrivalent and 9-valent vaccines also have demonstrated high efficacy against vaccine type-associated vaginal and vulvar intraepithelial neoplasia. They also protect against genital warts associated with HPV 6 and HPV 11. The efficacy of any HPV vaccine for the prevention of anal intraepithelial neoplasia has not been studied in females. (See 'Efficacy and immunogenicity in females' above.)

●We recommend HPV immunization of females, as advised by multiple expert panels (Grade 1A). If cost and availability are not issues, we recommend the 9-valent vaccine for females in whom HPV vaccination is indicated (Grade 1B). Routine immunization should be offered to girls 11 to 12 years of age, but can be administered as early as nine years. Catch-up vaccination should be offered for females aged 13 to 26 years who have not been previously vaccinated. (See 'Recommendations for HPV immunization in females' above.)

●Quadrivalent HPV vaccine is effective in preventing genital warts in young males and anal intraepithelial neoplasia among men who have sex with men (MSM). Immunogenicity of the 9-valent vaccine in males is similar to that in females. (See 'Efficacy and immunogenicity in males' above.)

●We recommend HPV vaccination in males, as advised by expert panels (Grade 1B). If cost and availability are not issues, we recommend the 9-valent vaccine for males in whom HPV vaccination is indicated (Grade 1B). Routine immunization should be offered to boys aged 11 to 12, but can be administered as early as nine years of age. Catch-up vaccination should be offered for males between the ages of 13 to 21 who have not been previously vaccinated. For MSM, catch-up vaccination should be offered up to age 26. (See 'Indications and choice of vaccine' above.)

●Although neither HPV vaccine contains live virus, use in pregnancy is not recommended because of limited data on safety. (See 'Pregnant females' above.)

●Serologic testing or HPV DNA testing is not required prior to immunization. (See 'Prevaccination assessment' above.)

●We suggest immunization of immunocompromised or immunosuppressed individuals with the HPV vaccine, including those with HIV infection, following the same guidelines as for immunocompetent patients (Grade 2C). Catch-up vaccination among these patients is recommended up to age 26 years. Cytologic screening continues to play an important role in detection and treatment of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ and prevention of cervical cancer in these high-risk patients. (See 'Immunization in special patient populations' above and "Screening for cervical cancer" and "Anal squamous intraepithelial lesions: Diagnosis, screening, prevention, and treatment".)

●The quadrivalent vaccine and 9-valent are administered in three doses at time zero, and at two and six months of follow-up. The bivalent vaccine is administered in three doses at time zero, and at one and six months of follow-up. (See 'Vaccine dose and administration' above.)

●In prelicensure clinical trials and postlicensure monitoring, vaccines have been demonstrated to be generally safe. (See 'Vaccine safety' above.)

●Cervical cancer screening is recommended for any woman 21 years of age or older. Clinicians should be aware that HPV immunization is not effective in clearing cytologically evident disease or HPV infection that is already present. (See 'Importance of cancer screening' above and "Screening for cervical cancer".)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Hoots BE, Palefsky JM, Pimenta JM, Smith JS. Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions. Int J Cancer 2009; 124:2375.
2. Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases. Vaccine 2012; 30 Suppl 5:F12.
3. Globocan 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Default.aspx.
4. Serrano B, Alemany L, Tous S, et al. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer 2012; 7:38.
5. Insinga RP, Glass AG, Rush BB. Diagnoses and outcomes in cervical cancer screening: a population-based study. Am J Obstet Gynecol 2004; 191:105.
6. de Sanjosé S, Alemany L, Ordi J, et al. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva. Eur J Cancer 2013; 49:3450.
7. De Vuyst H, Clifford GM, Nascimento MC, et al. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer 2009; 124:1626.
8. Alemany L, Saunier M, Alvarado-Cabrero I, et al. Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer 2015; 136:98.
9. Joseph DA, Miller JW, Wu X, et al. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer 2008; 113:2892.
10. Johnson LG, Madeleine MM, Newcomer LM, et al. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004; 101:281.
11. Robinson D, Coupland V, Møller H. An analysis of temporal and generational trends in the incidence of anal and other HPV-related cancers in Southeast England. Br J Cancer 2009; 100:527.
12. Jemal A, Simard EP, Dorell C, et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013; 105:175.
13. Daling JR, Weiss NS, Klopfenstein LL, et al. Correlates of homosexual behavior and the incidence of anal cancer. JAMA 1982; 247:1988.
14. Melbye M, Coté TR, Kessler L, et al. High incidence of anal cancer among AIDS patients. The AIDS/Cancer Working Group. Lancet 1994; 343:636.
15. Goedert JJ, Coté TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351:1833.
16. Brown DR, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis 2009; 199:926.
17. Insinga RP, Dasbach EJ, Myers ER. The health and economic burden of genital warts in a set of private health plans in the United States. Clin Infect Dis 2003; 36:1397.
18. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007; 356:1944.
19. Mork J, Lie AK, Glattre E, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 2001; 344:1125.
20. Gillison ML, Broutian T, Pickard RK, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 2012; 307:693.
21. Li X, Gao L, Li H, et al. Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis. J Infect Dis 2013; 207:479.
22. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29:4294.
23. Backes DM, Kurman RJ, Pimenta JM, Smith JS. Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control 2009; 20:449.
24. A human papillomavirus vaccine. Med Lett Drugs Ther 2006; 48:65.
25. FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm.
26. Cervarix--a second HPV vaccine. Med Lett Drugs Ther 2010; 52:37.
27. Trimble CL, Morrow MP, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet 2015.
28. Villa LL, Ault KA, Giuliano AR, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine 2006; 24:5571.
29. Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006; 367:1247.
30. GlaxoSmithKline Vaccine HPV-007 Study Group, Romanowski B, de Borba PC, et al. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet 2009; 374:1975.
31. Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015; 372:711.
32. Vesikari T, Brodszki N, van Damme P, et al. A Randomized, Double-Blind, Phase III Study of the Immunogenicity and Safety of a 9-Valent Human Papillomavirus L1 Virus-Like Particle Vaccine (V503) Versus Gardasil® in 9-15-Year-Old Girls. Pediatr Infect Dis J 2015; 34:992.
33. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007; 356:1928.
34. Gardasil 9 (Human papillomavirus 9-valent vaccine, recombinant. US FDA approved product information; Whitehouse Station, NJ: Merck & Co, Inc. December 2014.
35. Van Damme P, Olsson SE, Block S, et al. Immunogenicity and Safety of a 9-Valent HPV Vaccine. Pediatrics 2015; 136:e28.
36. Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant Vaccines and Related Biological Products Advisory Committee (VRBPAC) Briefing Document, September 9, 2009. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181371.pdf (Accessed on February 12, 2013).
37. Sow PS, Watson-Jones D, Kiviat N, et al. Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine: a randomized trial in 10-25-year-old HIV-Seronegative African girls and young women. J Infect Dis 2013; 207:1753.
38. Pedersen C, Petaja T, Strauss G, et al. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health 2007; 40:564.
39. Einstein MH, Baron M, Levin MJ, et al. Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years. Hum Vaccin 2009; 5:705.
40. Lin SW, Ghosh A, Porras C, et al. HPV16 seropositivity and subsequent HPV16 infection risk in a naturally infected population: comparison of serological assays. PLoS One 2013; 8:e53067.
41. Safaeian M, Porras C, Schiffman M, et al. Epidemiological study of anti-HPV16/18 seropositivity and subsequent risk of HPV16 and -18 infections. J Natl Cancer Inst 2010; 102:1653.
42. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007; 356:1915.
43. Paavonen J, Naud P, Salmerón J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009; 374:301.
44. Castle PE, Schmeler KM. HPV vaccination: for women of all ages? Lancet 2014; 384:2178.
45. Skinner SR, Szarewski A, Romanowski B, et al. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet 2014; 384:2213.
46. Kreimer AR, González P, Katki HA, et al. Efficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial. Lancet Oncol 2011; 12:862.
47. Herrero R, Quint W, Hildesheim A, et al. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One 2013; 8:e68329.
48. Centers for Disease Control and Prevention (CDC). Advisory Committee on Immunization Practices (ACIP) recommended immunization schedules for persons aged 0 through 18 years and adults aged 19 years and older--United States, 2013. MMWR Surveill Summ 2013; 62 Suppl 1:1.
49. Markowitz LE, Dunne EF, Saraiya M, et al. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63:1.
50. Petrosky E, Bocchini JA Jr, Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015; 64:300.
51. Saslow D, Castle PE, Cox JT, et al. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin 2007; 57:7.
52. Petäjä T, Keränen H, Karppa T, et al. Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged 10-18 years. J Adolesc Health 2009; 44:33.
53. Reisinger KS, Block SL, Lazcano-Ponce E, et al. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J 2007; 26:201.
54. Giuliano AR, Palefsky JM, Goldstone S, et al. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med 2011; 364:401.
55. Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 2011; 365:1576.
56. Gee J, Naleway A, Shui I, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. Vaccine 2011; 29:8279.
57. Kim JJ. Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis. Lancet Infect Dis 2010; 10:845.
58. Chesson HW, Ekwueme DU, Saraiya M, et al. The cost-effectiveness of male HPV vaccination in the United States. Vaccine 2011; 29:8443.
59. Centers for Disease Control and Prevention (CDC). Noninfluenza vaccination coverage among adults - United States, 2011. MMWR Morb Mortal Wkly Rep 2013; 62:66.
60. Castle PE, Scarinci I. Should HPV vaccine be given to men? BMJ 2009; 339:b4127.
61. Parkin DM, Bray F. Chapter 2: The burden of HPV-related cancers. Vaccine 2006; 24 Suppl 3:S3/11.
62. Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 2008; 113:3036.
63. Bogaards JA, Wallinga J, Brakenhoff RH, et al. Direct benefit of vaccinating boys along with girls against oncogenic human papillomavirus: bayesian evidence synthesis. BMJ 2015; 350:h2016.
64. Nielson CM, Flores R, Harris RB, et al. Human papillomavirus prevalence and type distribution in male anogenital sites and semen. Cancer Epidemiol Biomarkers Prev 2007; 16:1107.
65. Burchell AN, Richardson H, Mahmud SM, et al. Modeling the sexual transmissibility of human papillomavirus infection using stochastic computer simulation and empirical data from a cohort study of young women in Montreal, Canada. Am J Epidemiol 2006; 163:534.
66. Wilkin T, Lee JY, Lensing SY, et al. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis 2010; 202:1246.
67. Kahn JA, Xu J, Kapogiannis BG, et al. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis 2013; 57:735.
68. Kojic EM, Kang M, Cespedes MS, et al. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis 2014; 59:127.
69. Levin MJ, Moscicki AB, Song LY, et al. Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. J Acquir Immune Defic Syndr 2010; 55:197.
70. Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2012. Ann Intern Med 2012; 156:211.
71. Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization. Summary of the SAGE April 2014 meeting http://www.who.int/immunization/sage/meetings/2014/april/report_summary_april_2014/en/ (Accessed on April 04, 2014).
72. Kosalaraksa P, Mehlsen J, Vesikari T, et al. An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. Pediatr Infect Dis J 2015; 34:627.
73. Schilling A, Parra MM, Gutierrez M, et al. Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines. Pediatrics 2015; 136:e563.
74. Centers for Disease Control and Prevention (CDC). National and state vaccination coverage among adolescents aged 13-17 years--United States, 2011. MMWR Morb Mortal Wkly Rep 2012; 61:671.
75. Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA trials. Lancet Oncol 2015; 16:775.
76. Herweijer E, Leval A, Ploner A, et al. Association of varying number of doses of quadrivalent human papillomavirus vaccine with incidence of condyloma. JAMA 2014; 311:597.
77. Blomberg M, Dehlendorff C, Sand C, Kjaer SK. Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts: A Nationwide Study of 550,000 Young Girls. Clin Infect Dis 2015; 61:676.
78. Safaeian M, Porras C, Pan Y, et al. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res (Phila) 2013; 6:1242.
79. Neuzil KM, Canh do G, Thiem VD, et al. Immunogenicity and reactogenicity of alternative schedules of HPV vaccine in Vietnam: a cluster randomized noninferiority trial. JAMA 2011; 305:1424.
80. Lamontagne DS, Thiem VD, Huong VM, et al. Immunogenicity of quadrivalent HPV vaccine among girls 11 to 13 Years of age vaccinated using alternative dosing schedules: results 29 to 32 months after third dose. J Infect Dis 2013; 208:1325.
81. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309:1793.
82. Kjaer SK, Sigurdsson K, Iversen OE, et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res (Phila) 2009; 2:868.
83. Rowhani-Rahbar A, Mao C, Hughes JP, et al. Longer term efficacy of a prophylactic monovalent human papillomavirus type 16 vaccine. Vaccine 2009; 27:5612.
84. Naud PS, Roteli-Martins CM, De Carvalho NS, et al. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Hum Vaccin Immunother 2014; 10:2147.
85. Ferris D, Samakoses R, Block SL, et al. Long-term study of a quadrivalent human papillomavirus vaccine. Pediatrics 2014; 134:e657.
86. Frazer IH, Cox JT, Mayeaux EJ Jr, et al. Advances in prevention of cervical cancer and other human papillomavirus-related diseases. Pediatr Infect Dis J 2006; 25:S65.
87. Agency for Healthcare Research and Quality. Safety of Vaccines Used for Routine Immunization in the United States, July 2014. http://effectivehealthcare.ahrq.gov/ehc/products/468/1930/vaccine-safety-report-140701.pdf (Accessed on July 08, 2014).
88. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 2009; 302:750.
89. Centers for Disease Control and Prevention (CDC). Syncope after vaccination--United States, January 2005-July 2007. MMWR Morb Mortal Wkly Rep 2008; 57:457.
90. World Health Organization. Global Advisory Committee on Vaccine Safety statement on the continued safety of HPV vaccination. March 12, 2014. http://www.who.int/vaccine_safety/committee/topics/hpv/GACVS_Statement_HPV_12_Mar_2014.pdf (Accessed on September 04, 2014).
91. Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005; 6:271.
92. Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004; 364:1757.
93. http://www.cdc.gov/vaccinesafety/Vaccines/HPV/gardasil.html (Accessed on November 15, 2011).
94. Human Papillomavirus Vaccination Coverage Among Adolescent Girls, 2007–2012, and Postlicensure Vaccine Safety Monitoring, 2006–2013 — United States. MMWR Recomm Rep 2013; 62:591.
95. Klein NP, Hansen J, Chao C, et al. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med 2012; 166:1140.
96. Arnheim-Dahlström L, Pasternak B, Svanström H, et al. Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ 2013; 347:f5906.
97. Scheller NM, Pasternak B, Svanström H, Hviid A. Quadrivalent human papillomavirus vaccine and the risk of venous thromboembolism. JAMA 2014; 312:187.
98. Brotherton JM, Gold MS, Kemp AS, et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ 2008; 179:525.
99. Douglas RJ. Anaphylaxis following quadrivalent human papillomavirus vaccination - even safer than it appears. CMAJ 2008.
100. Kang LW, Crawford N, Tang ML, et al. Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study. BMJ 2008; 337:a2642.
101. Scheller NM, Svanström H, Pasternak B, et al. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA 2015; 313:54.
102. Schuler CL, Reiter PL, Smith JS, Brewer NT. Human papillomavirus vaccine and behavioural disinhibition. Sex Transm Infect 2011; 87:349.
103. Marlow LA, Forster AS, Wardle J, Waller J. Mothers' and adolescents' beliefs about risk compensation following HPV vaccination. J Adolesc Health 2009; 44:446.
104. Bednarczyk RA, Davis R, Ault K, et al. Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds. Pediatrics 2012; 130:798.
105. Smith LM, Kaufman JS, Strumpf EC, Lévesque LE. Effect of human papillomavirus (HPV) vaccination on clinical indicators of sexual behaviour among adolescent girls: the Ontario Grade 8 HPV Vaccine Cohort Study. CMAJ 2015; 187:E74.
106. Jena AB, Goldman DP, Seabury SA. Incidence of sexually transmitted infections after human papillomavirus vaccination among adolescent females. JAMA Intern Med 2015; 175:617.
107. National HPV vaccination program register. Coverage Data. Australia. http://www.hpvregister.org.au/research/coverage-data (Accessed on July 20, 2015).
108. Vaccine uptake guidance and the latest coverage data. Public Health England. https://www.gov.uk/government/collections/vaccine-uptake (Accessed on July 20, 2015).
109. Widgren K, Simonsen J, Valentiner-Branth P, Mølbak K. Uptake of the human papillomavirus-vaccination within the free-of-charge childhood vaccination programme in Denmark. Vaccine 2011; 29:9663.
110. Agénor M, Peitzmeier S, Gordon AR, et al. Sexual Orientation Identity Disparities in Awareness and Initiation of the Human Papillomavirus Vaccine Among U.S. Women and Girls: A National Survey. Ann Intern Med 2015; 163:99.
111. Niccolai LM, Hansen CE. Practice- and Community-Based Interventions to Increase Human Papillomavirus Vaccine Coverage: A Systematic Review. JAMA Pediatr 2015; 169:686.
112. American Cancer Society. Cancer Facts and Figures 2004. www.cancer.org/downloads/STT/CAFF_FinalPWSecured.pdf (Accessed on March 27, 2006).
113. Clinical management guidelines for the Obstetrician-Gynecologists. Cervical cytology screening. ACOG Practice Bulletin 2009;109. (Replaces Practice Bulletin Number 45, August 2003 and Committee Opinion Number 431, May 2009)
114. Sanders GD, Taira AV. Cost-effectiveness of a potential vaccine for human papillomavirus. Emerg Infect Dis 2003; 9:37.
115. Goldie SJ, Kohli M, Grima D, et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004; 96:604.
116. Kulasingam SL, Myers ER. Potential health and economic impact of adding a human papillomavirus vaccine to screening programs. JAMA 2003; 290:781.
117. Chesson HW, et al. Cost effectiveness models of HPV vaccines. May 9, 2006 - 2006 National STD Prevention Conference.
118. Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med 2008; 359:821.
119. Hughes JP, Garnett GP, Koutsky L. The theoretical population-level impact of a prophylactic human papilloma virus vaccine. Epidemiology 2002; 13:631.
120. Taira AV, Neukermans CP, Sanders GD. Evaluating human papillomavirus vaccination programs. Emerg Infect Dis 2004; 10:1915.
121. Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol 2008; 109:S15.
122. Newall AT, Beutels P, Wood JG, et al. Cost-effectiveness analyses of human papillomavirus vaccination. Lancet Infect Dis 2007; 7:289.

Topic 8325 Version 39.0

ALLERGY & CLINICAL IMMUNOLOGY / ALERGIA E INMUNOLOGIA

 

Allergy & Clinical Immunology

News & Perspective

Drugs & Diseases

CME & Education

Dr. C Mijares

Specialty Topics

• Asthma
• Atopic Dermatitis
• Inflammatory Bowel Disease

More

Also of Interest

• Healthcare Reform & the ACA
• Medical Practice Management
• Medicine 3.0

More

Today on Twitter

Trending Medical News from Around the Web

• 
  Survey: 43 percent of smartphone users interested in AI-powered medical advisor

  mobihealthnews.com

  12m

  

  Rock Health

  @Rock_Health

  43% of smartphone users are interested in an AI-powered medical advisor bit.ly/1OWtRnR pic.twitter.com/q4UbXsjPPa

  • 
    
  • 
    
  • 
    
• 
  Health Systems Built For The 1% Face Big Population Health Gaps

  www.forbes.com

  59m

  

  Dave Chase

  @chasedave

  RT @DocASAP Health Systems Built For The 1% Face Big #PopulationHealth Gaps - Patient centered transformation needed ow.ly/VAjh7

  • 
    
  • 
    
  • 
    

View All Trending Articles

Allergy & Clinical Immunology News

More

• Live Attenuated Vaccine Safe for Children With Egg Allergy A new study has found that live attenuated influenza vaccine is unlikely to trigger systemic anaphylaxis in children with egg allergy and well-controlled asthma.
  Medscape Medical News, December 9, 2015

  2 comments

• Alert EMA OKs Nucala for Severe Refractory Eosinophilic Asthma The European Medicines Agency has approved mepolizumab as an add-on treatment for severe refractory eosinophilic asthma in adults.
  International Approvals, December 3, 2015
• Novel Computer Tool Improves Asthma Counseling in Low-Literacy Patients A novel computer-generated written asthma action plan (WAAP) that uses pictures and photographs can improve asthma counseling to low-literacy patients, a new study finds.
  Reuters Health Information, December 3, 2015

• IBD: Skin Issues From Anti-TNF Therapy Should Be Addressed
  Medscape Medical News, December 11, 2015
• Death Rates Down for Many, Hit Record Low for US Infants
  Medscape Medical News, December 11, 2015

  2 comments
• FDA Panel Backs Reslizumab for Adults With Severe Asthma
  Medscape Medical News, December 10, 2015

  1 comment
• Collaborative Approach Reduces Unneeded Bronchiolitis Care
  Medscape Medical News, December 10, 2015

  1 comment

 

Today on Medscape

Top Stories from Across Medicine

More

• Gabapentin New Drug of Abuse?The nonmedical use of gabapentin is on the rise, particularly among substance abuse patients in rehabilitation programs, researchers say.
  Medscape Medical News, December 11, 2015

  3 comments

• Opioids for Chronic Pain: Yes or No?
  Medscape Rheumatology

  1 comment
• BRAIN Initiative Update: 'Leapfrog' Progress
  Medscape Medical News, December 11, 2015

• The Biggest Infectious Disease Threats
  Medscape Family Medicine
• Three-Year Major Bleeding Risk Same With Watchman or Warfarin
  Heartwire from Medscape, December 11, 2015

Business of Medicine

More

• Medicare Penalizes 758 Hospitals for Safety Deficiencies Hospital-acquired condition program reduces Medicare payments 1%; some improvement seen in HAC prevalence.
  Medscape Medical News, December 10, 2015
• Reader Poll: What Questions Do You Have About ICD-10?
  Medscape Medical News, December 10, 2015

  4 comments
• ACP Reiterates Stance on Gun Violence in NYT Letter
  Medscape Medical News, December 10, 2015

  18 comments
• Reader Poll: Increasing Burnout at Your Practice?
  Medscape Medical News, December 4, 2015

  49 comments

• Dermatologists Wary Despite Low Malpractice Risks; More Liability concerns affect even the least likely to be sued; these doctors want to see the public vote on caps; hospital's failure to diagnose leads to a fat award.
  Medscape Business of Medicine, December 10, 2015

  1 comment
• Should Patients Call You by Your First Name? In an age where everyone seems to lean toward being less formal, many physicians still don't feel comfortable with patients using their first name in medical settings. Your colleagues weigh in.
  Medscape Business of Medicine, December 9, 2015

  2 comments

Columnists

• Oral Allergy Syndrome: When an Apple a Day Is Not Advised
• Bright-Light Therapy in Dementia
• Patient-Generated Data: How's a Doctor to Interpret It All?  

Advisory Board

• Bradley E. Chipps, MD
• Erwin W. Gelfand, MD
• Michael A. Kaliner, MD

• Gary J. Stadtmauer, MD
• William W. Storms, MD

Site Editorial Director

• Marrecca Fiore

Medscape Editor-in-Chief

• Eric J. Topol, MD Director, Scripps Translational Science Institute; Chief Academic Officer, Scripps Health; Professor of Genomics, The Scripps Research Institute, La Jolla, California

Medscape Staff

Allergy & Clinical Immunology Perspective & Journal Articles

More

• Factors Involved in Airway Inflammation in Allergic Asthma This study investigates the contribution of these transcription factors in the pathogenesis of late-phase airway inflammation in adult allergic asthma patients.
  BMC Pulmonary Medicine, December 9, 2015
• Oral Allergy Syndrome: When an Apple a Day Is Not Advised
  Medscape Allergy & Immunology, December 10, 2015
• Can Weight Loss Improve Asthma?
  Medscape Pulmonary Medicine, December 9, 2015

  1 comment
• The Year in Medicine 2015: News That Made a Difference
  Medscape News Slideshows, December 2, 2015

 

 

Allergy & Clinical Immunology Blogs

• Old Dilemma: Asthma with irreversible airways obstruction vs COPD 
  From Atopic Topics , Posted at 11:45:33, October 31. 1 Comment
• How Did You Spend October 1? 
  From Atopic Topics , Posted at 21:10:25, October 1. 4 Comments

Most Popular Articles

1. FDA OKs Fluad, First Seasonal Influenza Vaccine With an Adjuvant
2. You're Allergic to What? New Food Allergies Emerging
3. Children With Nut Allergies: One Size Does Not Fit All
4. Where You Live Affects Survival After Pancreatic Cancer Surgery
5. Vaccination to Protect Against Infection of the Female Reproductive Tract

Medscape Editorial Collaborations

• Centers for Disease Control and Prevention
• Food and Drug Administration

• • 
    
  • 
    
  • 
    
  • 
    
  • 
    

• About

  • About Medscape
  • Privacy Policy
  • Terms of Use
  • Help Center

• Membership

  • Email Newsletters
  • Manage My Account

• Apps

  • Medscape
  • MedPulse News
  • CME & Education
  • Business of Medicine

• WebMD Network

  • WebMD
  • MedicineNet
  • eMedicineHealth
  • RxList
  • WebMD Corporate

• Editions

  • English
  • Français
  • Deutsch

All material on this website is protected by copyright, Copyright © 1994-2015 by WebMD LLC. This website also contains material copyright

LOS NIÑOS CON ASMA Y ALERGIAS PODRIAN TENER PROBLEMAS CARDIACOS

Busque en MedlinePlus

• Sobre MedlinePlus
• Índice
• FAQs
• Contáctenos

• Temas de salud
• Medicinas y suplementos
• Videos y multimedia

English

Usted esta aquí:

Página Principal →

Últimas noticias de salud →

Noticia

Los niños con asma y alergias podrían tener más factores de riesgo de problemas cardiacos, según un estudio

El riesgo de colesterol alto y de hipertensión se duplica en esos casos, pero el peligro para cualquier niño en particular es bajo, según los hallazgos

Traducido del inglés: miércoles, 9 de diciembre, 2015

MARTES, 8 de diciembre de 2015 (HealthDay News) -- Un nuevo estudio sugiere que el riesgo de hipertensión y colesterol alto de los niños con asma o alergias, como la fiebre del heno, podría ser más del doble, aunque no tengan sobrepeso.
Pero el riesgo de cualquier niño en particular sigue siendo bajo, enfatizaron los expertos, y no está claro si las enfermedades alérgicas provocan directamente estos problemas. Es posible que otro factor (como la falta de ejercicio) esté influyendo.
Aun así, el autor del estudio, el Dr. Jonathan Silverberg, dijo que "hay problemas de salud comunes que resultan tener consecuencias mucho más graves en algunos niños".
Según Silverberg, profesor asociado de dermatología de la Facultad de Medicina Feinberg de la Universidad de Northwestern, en Chicago, las investigaciones previas han mostrado que los adultos con trastornos alérgicos son más propensos a tener factores de riesgo de enfermedades cardiacas. Las investigaciones que ha hecho han sugerido vínculos entre la afección de la piel llamada eczema y estilos de vida no saludables, como tener una menor actividad física y fumar, y los factores de riesgo de las enfermedades cardiacas. El nuevo estudio se propone comprender si en los niños se producen unas conexiones parecidas.
Para averiguarlo, el equipo de Silverberg examinó los resultados de una encuesta estadounidense de 2012 realizada en hogares y se centró en los hallazgos sobre más de 13,000 niños de hasta 17 años de edad. La encuesta halló que aproximadamente un 14 por ciento de los niños en ese rango de edad tenían asma, un 12 por ciento tenían eczema y el 16 por ciento, fiebre del heno.
El nuevo estudio ha descubierto que los niños con asma y fiebre del heno tenían más probabilidades que otros niños de ser obesos o tener sobrepeso, y también tenían aproximadamente el doble de riesgo de hipertensión y colesterol alto.
Siguió habiendo un riesgo adicional incluso después de que los investigadores tuvieran en cuenta la obesidad como factor en sus cálculos estadísticos, señaló el grupo de Silverberg. Pero los niños no tuvieron un riesgo más alto de diabetes.
Y el aumento real en el riesgo de hipertensión y el colesterol alto no era grande. Para los niños con asma y fiebre del heno, el nivel general de riesgo solo creció en más o menos un punto de porcentaje, indicaron los investigadores.
De modo que, "claramente, no todos los niños con enfermedades alérgicas tienen más enfermedades cardiovasculares", dijo Silverberg. "En función de otros estudios, sospechamos que se trata principalmente de los niños con enfermedades más graves, aunque no pudimos examinarlo en este estudio en particular".
Los niños con otra enfermedad autoinmune (el eczema, una enfermedad de la piel) no parecían tener un riesgo más alto de colesterol alto e hipertensión. Pero tendían a ganar más peso adicional.
Pero, ¿qué podría vincular a las alergias, el asma y los problemas cardiacos?
Es posible que la inflamación relacionada con las alergias pudieran aumentar el nivel de colesterol y de presión arterial, dijo el Dr. Gregg Fonarow, profesor de cardiología en la Universidad de California, en Los Ángeles. De hecho, algunos investigadores han vinculado enfermedades como la psoriasis, que provocan inflamación, con un aumento del riesgo de enfermedades cardiacas, indicó.
Silverberg dijo que también es posible que las enfermedades podrían provocar problemas de otros modos, como, por ejemplo, dormir mal.
Por su parte, Fonarow especuló con que las diferencias en la actividad física, la dieta y la ingesta calórica entre los niños con y sin las afecciones podrían marcar una diferencia.
¿Qué se puede hacer?
Fonarow dijo que los padres no deberían estar especialmente preocupados por los hallazgos. Pero Silverberg dijo que los padres deberían comprender que las enfermedades relativas a las alergias, sobre todo cuando son graves, pueden llevar a otros problemas de salud.
"Es importante reconocer estos efectos dañinos para prevenirlos o tratarlos temprano", señaló. "Los padres deberían hablar con su pediatra y los especialistas si su hijo tiene una enfermedad alérgica que no esté bien controlada o si notan que sus hijos, a causa de la enfermedad alérgica, están aumentando de peso o no pueden hacer cosas que otros niños de su edad sí pueden hacer".
Y los médicos podrían hacer pruebas de hipertensión y colesterol a los niños con enfermedades alérgicas graves, comentó.
El estudio apareció el 8 de diciembre en la revista Journal of Allergy & Clinical Immunology.

Artículo por HealthDay, traducido por Hola Doctor

FUENTES: Jonathan Silverberg, M.D., Ph.D., MPH, associate professor, dermatology, Northwestern University Feinberg School of Medicine, Chicago; Gregg Fonarow, M.D., professor, cardiology, University of California, Los Angeles. Dec. 8, 2015, Journal of Allergy & Clinical Immunology

HealthDay

(c) Derechos de autor 2015, HealthDay

Más noticias de salud en:

Alergia

Asma en niños

Salud del niño

Últimas noticias de salud

Temas de salud relacionados

• Alergia
• Asma en niños
• Salud del niño

• Anuncios de MedlinePlus por email
• RSS
• Síganos en Twitter

• Exenciones
• Derechos de autor
• Política de privacidad
• Accesibilidad
• Criterios de calidad
• Visores y reproductores

U.S. National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health

Página actualizada 10 diciembre 2015

MEDICINAS PARA EL VIH / SIDA / HIV / AIDS

Busque en MedlinePlus

• Sobre MedlinePlus
• Índice
• FAQs
• Contáctenos

• Temas de salud
• Medicinas y suplementos
• Videos y multimedia

English

Usted esta aquí:

Página Principal →

Temas de salud →

Medicinas para el VIH/SIDA

Medicinas para el VIH/SIDA

Otros nombres: Medicamentos para el SIDA, Medicamentos para el VIH/SIDA, Remedios para el SIDA, Remedios para el VIH/SIDA 

En esta página

Entérese

• Introducción
• Comience aquí
• Últimas noticias
• Diagnósticos/Síntomas
• Prevención/Exámenes
• Tratamientos y terapias

Para saber más

• Asuntos relacionados
• Condiciones específicas

Para ver, jugar y aprender

• Imágenes

Investigaciones

• Información no disponible

Recursos

• Información de referencia
• Especialistas

Para usted

• Información no disponible

Introducción

A comienzos de la década de los '80, cuando comenzó la epidemia del VIH/SIDA, los pacientes raramente vivían más de algunos años. Pero actualmente, existen tratamientos y medicamentos efectivos para combatir la infección y las personas infectadas con VIH tienen vidas más largas y sanas.
Existen cinco clases principales de medicamentos:

• Inhibidores de la transcriptasa reversa (RT, por sus siglas en inglés): Interfieren con un paso importante del ciclo de vida del VIH e impiden que el virus multiplique copias de sí mismo
• Inhibidores de la proteasa: Interfieren con una proteína que usa el VIH para producir partículas virales infecciosas
• Inhibidores de fusión: Bloquean la entrada del virus a las células del cuerpo
• Inhibidores de integrasa: Bloquean la integrasa, una enzima que necesita el VIH para multiplicarse
• Combinaciones de varios medicamentos: Contienen dos o más medicamentos pertenecientes a una o más clases

Estos medicamentos ayudan a las personas con VIH pero no son perfectos. No curan las infecciones por VIH/SIDA. Las personas con infecciones por VIH aún tienen el virus en el cuerpo, de modo que incluso cuando toman medicinas pueden transmitir el VIH a otras personas a través de las relaciones sexuales sin protección y de agujas compartidas.

NIH: Instituto Nacional de Alergias y Enfermedades Infecciosas

Comience aquí

• Base de datos de medicamentos infoSIDA (InfoSIDA) Disponible en inglés
• ¿Cómo tomar los antirretrovirales disponibles? (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• ¿Es curable la infección por el VIH? (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Nombres y fabricantes de los medicamentos contra el VIH (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Pautas para terapia contra el VIH en los EE.UU. (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Regímenes terapéuticos recomendados para el VIH (InfoSIDA) Disponible en inglés
• Terapia antirretroviral (TARV) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• VIH y SIDA: Cómo tomar medicamentos para el VIH (Academia Americana de Médicos de Familia)

Últimas noticias

• Quizá no haya que tomar una pastilla a diario para prevenir el VIH (02/12/2015, HealthDay)
• Tratamiento preventivo contra el VIH muestra su efectividad en clínicas de salud (17/11/2015, HealthDay)
• FDA aprueba nuevo tratamiento para el VIH (05/11/2015, Administración de Alimentos y Medicamentos)
• Terapia contra el VIH podría también reducir el riesgo de hepatitis B (13/10/2015, HealthDay)
• Más noticias sobre Medicinas para el VIH/SIDA

Diagnósticos/Síntomas

• Análisis de composición corporal (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• Análisis de resistencia del VIH (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés

Prevención/Exámenes

• Una pastilla diaria puede prevenir el VIH (Centros para el Control y la Prevención de Enfermedades) Disponible en inglés

Tratamientos y terapias

• Acupuntura china (para personas con VIH) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Terapias alternativas (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés

Asuntos relacionados

• Adherencia al tratamiento (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Atención para el VIH salva vidas (Centros para el Control y la Prevención de Enfermedades) Disponible en inglés
• Azúcar en la sangre y grasas (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• ¿Cómo afecta al VIH el uso de drogas recreativas? (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• ¿Cómo identificar fraude relacionado al VIH/SIDA? (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Complera / Eviplera (rilpivirina, emtricitabina, tenofovir) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Efectos secundarios (de los medicamentos antirretrovirales) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• Erupción cutánea (InfoSIDA)
• Hepatotoxicidad (InfoSIDA)
• Hiperlipidemia (InfoSIDA)
• Infección por el VIH y la diabetes (InfoSIDA)
• Interacciones entre medicamentos (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• Interrupciones del tratamiento (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Lipodistrofia (InfoSIDA) - PDF
• Medicamentos contra el VIH y sus efectos secundarios (InfoSIDA)
• Neuropatía periférica (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• Resistencia a los medicamentos (InfoSIDA) Disponible en inglés
• Toxicidad mitocondrial (TM) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México) Disponible en inglés
• VIH y SIDA: Prueba de carga viral en plasma (Academia Americana de Médicos de Familia)

Condiciones específicas

• Boceprevir (Victrelis) (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• Combinaciones en dosis fija (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)
• PEP (profilaxis posexposición) 101 (Academia Americana de Médicos de Familia) Disponible en inglés
• Profilaxis de prexposición (PrEP) (Centros para el Control y la Prevención de Enfermedades) Disponible en inglés
• Tratamiento después de exposición (Centro para la Educación y Entrenamiento sobre el SIDA de Nuevo México)

Imágenes

• Fármacos que combaten el VIH (Instituto Nacional de Alergias y Enfermedades Infecciosas) - PDF

Información de referencia

• Glosario de InfoSIDA (InfoSIDA) Disponible en inglés

Especialistas

• InfoSIDA (Departamento de Salud y Servicios Humanos) Disponible en inglés

Tema Imagen

MedlinePlus actualizaciones por email

Reciba actualizaciones sobre Medicinas para el VIH/SIDA por email ¿Qué es esto?

Temas de salud rel