Human Papillomavirus Vaccination UpToDate

9/4/2018 Human papillomavirus vaccination - UpToDate
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Human papillomavirus vaccination
Authors: J Thomas Cox, MD, Joel M Palefsky, MD

Section Editor: Martin S Hirsch, MD
Deputy Editor: Allyson Bloom, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2018. | This topic last updated: Mar 09, 2018.
INTRODUCTION — Human papillomavirus (HPV) is a sexually transmitted pathogen that causes anogenital and oropharyngeal disease in males and
females. Persistent viral infection with high-risk HPV genotypes causes virtually all cancers of the cervix. The high-risk HPV genotypes (or "types") 16
and 18 cause approximately 70 percent of all cervical cancers worldwide, and types 31, 33, 45, 52, and 58 cause an additional 20 percent. HPV types
16 and 18 also cause nearly 90 percent of anal cancers and a significant proportion of oropharyngeal cancer, vulvar and vaginal cancer, and penile
cancer. HPV types 6 and 11 cause approximately 90 percent of anogenital warts.
Vaccines have been developed to protect against acquisition of HPV infection and development of subsequent HPV-associated disease. This topic will
cover issues related to routine immunization recommendations, vaccination in special patient populations, and vaccine safety.
The natural history, epidemiology, and disease associations of HPV infection are discussed elsewhere. (See "Human papillomavirus infections:
Epidemiology and disease associations".)
AVAILABLE VACCINES — Three different vaccines, which vary in the number of HPV types they contain and target, have been clinically developed,
although not all are available in all locations:
● Quadrivalent HPV vaccine (Gardasil) targets HPV types 6, 11, 16, and 18.
● 9-valent vaccine (Gardasil 9) targets the same HPV types as the quadrivalent vaccine (6, 11, 16, and 18) as well as types 31, 33, 45, 52, and 58.
● Bivalent vaccine (Cervarix) targets HPV types 16 and 18.
In the United States, only the 9-valent vaccine is available. Practitioners in other locations should confirm vaccine availability locally.
Dosing and administration is discussed elsewhere. (See 'Administration' below.)
These are all prophylactic vaccines, designed to prevent initial 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 [1].
RATIONALE
Females — Vaccination with 9-valent, quadrivalent, or bivalent HPV vaccine provides a direct benefit to female recipients by safely protecting against
cancers that can result from persistent HPV infection. This preventive effect is most notable and best studied with cervical cancer, which is one of the
most common female cancers worldwide. HPV types 16 and 18, which are targeted by all three HPV vaccines, cause approximately 70 percent of all
cervical cancers worldwide, and HPV types 31, 33, 45, 52, and 58, which are additionally targeted by the 9-valent vaccine, cause an additional 20
percent. HPV types 16 and 18 also cause nearly 90 percent of anal cancers and a substantial proportion of vaginal, vulvar, and oropharyngeal cancers.
Vaccination with the quadrivalent or 9-valent HPV vaccine also protects against anogenital warts (90 percent of which are caused by HPV types 6 and
11); although they are benign lesions, they are associated with physical and psychological morbidity and have a high rate of treatment failure. The
adverse effects of HPV vaccination are generally limited to mild local reactions. Vaccine efficacy and safety are discussed below. (See 'Efficacy' below
and 'Vaccine safety' below.)
Details on HPV-associated diseases and the burden of HPV infection among females are found elsewhere. (See "Human papillomavirus infections:
Various modeling studies have outlined the potential benefits of HPV vaccination, which appear to be cost effective for the recommended age range [2-
6]. 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 [2]. In settings where there has been high uptake of vaccine among females there is also evidence of herd immunity among males of
similar age, reflected by a reduction in genital warts [7].
Males — HPV vaccination provides a direct benefit to male recipients by safely protecting against cancers that can result from persistent HPV
infection. HPV types 16 and 18 cause nearly 90 percent of anal cancers and substantial proportion of oropharyngeal and penile cancers. Vaccination
with 9-valent or quadrivalent vaccine also protects against anogenital warts (90 percent of which are caused by HPV types 6 and 11). The overall
burden of HPV-associated cancers and precancers among males is less than the burden of cervical cancer in females. Nevertheless, despite a smaller
direct absolute benefit of HPV vaccination in males compared with females, the overall benefit of vaccinating males outweighs its potential risks
because of additional population benefits from herd immunity and the documented safety of HPV vaccines. (See 'Vaccine safety' below and 'Efficacy'
below.).
Details on HPV-associated diseases and the burden of HPV infection among males are found elsewhere. (See "Human papillomavirus infections:
Various models have indicated that vaccinating both males and females is more beneficial in reducing HPV infection and disease than by vaccinating
only females, although male vaccination is less cost effective than female vaccination [8-14]. However, cost-effectiveness analyses are limited by
uncertainty regarding different variables that affect the impact of male vaccination. These include vaccine efficacy and duration of protection, vaccine
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coverage of females, the effect of herd immunity, the range of health outcomes included, and the effect of HPV-associated diseases on quality of life
[15].
In particular, models have found that the cost-effectiveness of male vaccination is higher in the setting of lower levels of female coverage. This is
because there would be less herd protection from female vaccination, and thus males would have more direct benefit from vaccination. In one study
that used population data from the Netherlands, the burden of HPV-associated cancers in men could be reduced by an estimated 37 and 66 percent if
vaccine uptake among girls and young women reached 60 and 90 percent, respectively, but vaccine uptake among females is considerably less than
60 percent in many locations [13]. Furthermore, even if vaccine uptake were sufficiently high among females to confer protection against males, this
would have minimal effect on men who have sex with men, who have substantially higher rates of HPV-associated anal cancer and precursor lesions
than heterosexual males.
In resource-limited settings, expert groups recommend that public health efforts focus primarily on vaccinating young females, the group in which the
absolute benefit and cost-effectiveness of HPV vaccination is the highest.
ADMINISTRATION
Indications and age range — In accordance with the Advisory Committee on Immunization Practices (ACIP) in the United States, we recommend
routine HPV vaccination for all females and males [16-19]. The ACIP recommended age ranges for vaccination are as follows:
● Females – HPV vaccine is recommended at 11 to 12 years. It can be administered starting at 9 years of age, and catch-up vaccination is
recommended for females aged 13 to 26 years who have not been previously vaccinated or who have not completed the vaccine series.
● Males – HPV vaccine is recommended at 11 to 12 years. It can be administered as starting at 9 years of age, and catch-up vaccination is
recommended for males aged 13 to 21 years who have not been previously vaccinated or who have not completed the vaccine series.
Among males 22 to 26 years old, catch-up HPV vaccination is recommended if they are men who have sex with men or immunocompromised
(including HIV-infected males). Otherwise, "permissive use" of HPV vaccination is recommended for this age range. 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 may not be covered by a patient's health insurance provider.
The main reason that routine catch-up HPV vaccination is not recommended for individuals older than 26 years is the increased likelihood of prior
exposure to HPV vaccine types with age, which reduces the potential individual benefit and thus the cost-effectiveness of HPV vaccination. However,
for some individuals in this age group, such as those with no prior sexual experience or certain lifelong sexual monogamy, the risk of prior HPV
exposure may be very low. We offer HPV vaccination to such individuals, as it may be beneficial if they are deemed to have a future risk of HPV
exposure; studies have suggested that HPV vaccination is immunogenic, efficacious, and safe in older women [20-23]. However, clinicians and
patients should be aware that HPV vaccination of individuals older than 26 years may not be covered by insurance providers or other payers.
These recommendations are consistent with other expert groups in the United States, including the American Academy of Pediatrics (AAP), the
American Academy of Family Practice (AAFP), the American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society
(ACS), and the International Papillomavirus Society [24-28]. These are also largely consistent with recommendations for resource-rich settings from
the American Society of Clinical Oncology (ASCO) guidelines on cervical cancer prevention [29].
Recommendations from other expert groups for resource-limited settings are somewhat different. The World Health Organization (WHO) recommends
that the primary target of HPV vaccination programs be females aged 9 to 14 years and 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 [30]. ASCO recommendations for resource-limited settings are similar [29].
Optimal timing — Within the recommended age range, the optimal time for HPV immunization is prior to an individual's sexual debut. 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"). None of the available HPV vaccines treat or accelerate the clearance of preexisting vaccine-type HPV
infections or related disease. (See 'Indications and age range' above.)
Individuals 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 [17]. However, immunization is less beneficial for those who have
already been infected with one of more of the HPV vaccine types. (See 'Preexisting HPV-associated disease' below.)
Choice of vaccine — Not all HPV vaccines are available in all locations. If cost and availability are not an issue, we recommend the 9-valent vaccine.
In the United States only the 9-valent vaccine is available (since 2017). The greater HPV-type coverage provided by the 9-valent compared with the
quadrivalent and bivalent vaccines protects against additional cervical cancers. Although it is not clear that greater HPV-type coverage by vaccinating
males with the 9-valent rather than quadrivalent vaccine would substantially improve male cancer prevention, it would likely further reduce the risk of
cervical cancer in women indirectly through herd immunity.
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
[18].
Revaccination with the 9-valent vaccine is likely of marginal individual benefit for those who have already completed the series with a different HPV
vaccine.
Immunization schedule — In the United States, the recommended dosing schedule depends on the age of the patient at vaccine initiation [16,17,19]:
● Individuals initiating the vaccine series before 15 years of age – Two doses of HPV vaccine should be given at 0 and at 6 to 12 months.
If the second dose was administered less than five months after the first, the dose should be repeated a minimum of 12 weeks after the second
dose and a minimum of five months after the first.
● Individuals initiating the vaccine series at 15 years of age or older – Three doses of HPV vaccine should be given at 0, 1 to 2 (typically 2),
and 6 months.
The minimum intervals between the first two doses is four weeks, between the second and third doses is 12 weeks, and between the first and third
dose is five months. If a dose was administered at a shorter interval, it should be repeated once the minimum recommended interval since the
most recent dose has passed.
● Immunocompromised patients – Three doses of HPV vaccine should be given at 0, 1 to 2, and 6 months regardless of age. (See
'Immunocompromised hosts' below.)
This ACIP recommended vaccination schedule is the same as that recommended by the Strategic Advisory Group of Experts on Immunizations
(SAGE) of the World Health Organization (WHO) [31]. The two-dose series is similarly recommended in many other countries. Practitioners outside the
United States should consult local guidelines for the recommended immunization schedule in their country.
HPV vaccine can be safely administered at the same time as other age-appropriate vaccines at a different anatomic site. 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 [32,33].
Although the initial clinical efficacy studies evaluated a three-dose schedule (see 'Efficacy' below), subsequent studies found that two vaccine doses in
young individuals have similar or greater immunogenicity compared with three doses in older females (the group in whom vaccine efficacy was
established in clinical trials) [34-38]. For the quadrivalent vaccine, furthermore, two doses are comparably effective as three doses for prevention of
genital warts [39,40]. There have been no studies directly evaluating the efficacy of fewer than three doses for prevention of cervical neoplastic
disease. Three doses of HPV vaccine are still recommended for individuals 15 and older because of the lower immunologic response to HPV
vaccination in this population.
As an example of supportive evidence for the two-dose schedule, a trial of 1518 participants randomly assigned to receive the 9-valent vaccine at
different dosing schedules demonstrated that antibody titers for HPV vaccine types were consistently higher among females and males aged 9 to 14
years who received two vaccine doses spaced 6 or 12 months apart compared with females aged 16 to 26 years who received three vaccine doses
over six months [37]. One cohort of females aged 9 to 14 years in this trial was also assigned to receive three vaccine doses; among females in this
age group, antibody responses were generally comparable with two- versus three-vaccine doses, and many vaccine-type titers trended higher with two
doses.
While no efficacy studies have been conducted to directly evaluate a two-dose schedule, a post hoc 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 suggests that two vaccine doses can effectively
protect against HPV infection [41]. Of those with at least 12 months of follow-up, vaccine efficacy against six-month persistent infection with HPV types
16 and 18 was no different in women who received the intended three doses compared with those who received only two (89 and 90 efficacy,
respectively).
Observational studies have examined effectiveness by number of doses, but are difficult to evaluate primarily because of a number of unmeasured
confounders. One observational study of over one million Swedish females suggested that two quadrivalent vaccine doses provided substantial
protection against genital warts, although completion of three doses was slightly superior (128 versus 174 events per 100,000 person-years with two
doses, compared with 528 events per 100,000 years without vaccination) [39]. 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 [40].
Missed doses — Patients often do not follow up for their immunizations on schedule [42]. The ACIP recommends that if the vaccination series is
interrupted for any length of time, it can be resumed without restarting the series.
Postvaccination instructions — Because of a potential for syncope with any vaccine, and particularly with the HPV vaccine, a routine 15-minute
waiting period in a sitting or supine position following HPV vaccination is recommended [17]. This may decrease the risk of syncope with subsequent
injury. (See 'Vaccine safety' below.)
Unnecessary evaluation
Prevaccination assessment — HPV vaccination can be administered without special evaluation. Serologic or HPV DNA testing is not warranted
prior to immunization [17]. Pregnancy testing is also not necessary.
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.
SPECIAL POPULATIONS
Pregnant or breastfeeding females — HPV vaccination during pregnancy is not recommended because of limited information about safety; however,
data from inadvertent use in this setting are increasingly available and reassuring. Thus, if a woman is found to be pregnant after initiating the
vaccination series, she can be reassured that available evidence does not indicate any increase in risk of adverse pregnancy outcome with
vaccination. Nevertheless, the remainder of the series should be delayed until the woman is no longer pregnant. This is discussed in detail elsewhere.
(See "Immunizations during pregnancy", section on 'Human papillomavirus'.)
Lactating females can receive the immunization series since subunit vaccines do not affect the safety of infant breastfeeding.
In the United States, the 9-valent vaccine manufacturer maintains a registry to monitor fetal outcomes of pregnant females exposed to HPV vaccine
[17,18]; prenatal exposures to the 9-valent vaccine can be reported by calling 800-986-8999.
Preexisting HPV-associated disease — A history of genital warts, a positive HPV test result, or abnormal cervical, vaginal, vulvar, or anal cytology all
indicate a prior HPV infection but not necessarily with the HPV types included in the vaccines. Vaccination is still recommended in individuals within the
recommended age range who have evidence of prior HPV infection, as it can still provide protection against infection with HPV vaccine types not
already acquired [16,17].
However, these patients should be advised that vaccination will have no therapeutic effect on preexisting HPV infection or HPV-associated disease,
and the potential benefit of HPV vaccination is not as great as if they were vaccinated before their sexual debut. (See 'Optimal timing' above.)
Immunocompromised hosts — Immunocompromised patients, particularly transplant recipients and HIV-infected patients with CD4 cell counts <200
cells/microL, are at especially high risk for HPV-related disease [43]. HPV vaccination with a three-dose schedule (at 0, 1 to 2, and 6 months) is
recommended for all immunocompromised patients through 26 years of age if they have not already been vaccinated. Immunocompromising
conditions that warrant this three-dose schedule include B-lymphocyte antibody deficiencies, complete or partial T-lymphocyte defects, HIV infection,
malignant neoplasm, transplantation, autoimmune disease, and immunosuppressive therapy.
Direct efficacy data on HPV vaccination in immunocompromised hosts are lacking. However, studies of the HPV quadrivalent vaccine in HIV-infected
adult men [44], HIV-infected women aged 16 to 23 years [45,46], and HIV-infected boys and girls aged 7 to 12 years [47] suggest that it is both
immunogenic and safe in these populations. Studies in other immunocompromised populations are ongoing.
HPV vaccination in transplant recipients is discussed in detail 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'.)
Cancer screening continues to play an important role in detection and treatment of HPV-associated disease in these high-risk individuals. (See
'Importance of cancer screening' below.)
EFFICACY AND IMMUNOGENICITY
Immunogenicity — Excellent antibody responses have been reported following immunization with the 9-valent, quadrivalent, and bivalent vaccines,
with seroconversion rates of 93 to 100 percent in females and 99 to 100 percent in males [48-52]. Elicited titers are generally higher in younger than in
older individuals. Although there is no defined minimum threshold titer for protection, seroconversion from prior exposure has been shown to reduce
the risk of incident HPV infection with the same HPV type [53,54]. This suggests 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 against reinfection with the same HPV type.
Because initial efficacy trials were restricted to sexually active females 15 years of age and older, immunological "bridging" studies conducted in
younger females and in males demonstrate safety and immunogenicity and thus support vaccine use in these other populations. With each of the three
vaccines, the geometric mean titers (GMT) of postvaccination antibodies among females aged 9 to 15 years were generally twofold higher than those
observed in females aged 16 to 26 for all targeted HPV types [50,55-59]. Similarly, GMT of postvaccination antibodies among males ages 9 to 26 were
at least comparable to those in females aged 16 to 26 years [50-52,56].
In a head-to-head comparison of the immunogenicity of quadrivalent and bivalent HPV vaccines in females ages 18 to 45 years, immunization with the
bivalent vaccine induced GMT 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 [60]. However, whether the induction of higher serum titers against HPV 16 and 18 has any impact on
the degree and duration of protection is unknown.
Efficacy
Cervical, vaginal, and vulvar disease — HPV vaccination is effective in preventing cervical disease, including cervical intraepithelial neoplasia
(CIN2 or 3) and adenocarcinoma in situ. This has been demonstrated in large randomized trials of quadrivalent, 9-valent, and bivalent vaccines and, as
discussed below, has been supported by population data from regions reporting declines in incidence of cervical disease following widespread
quadrivalent HPV vaccination. In addition, quadrivalent and 9-valent HPV vaccines have been demonstrated to reduce the incidence of vaginal and
vulvar intraepithelial neoplasia (VAIN and VIN 1-3). Vaccine efficacy is greatest in those who do not have prior HPV infection.
In the large licensing trials for the HPV vaccines, baseline HPV infection status was determined through serologic testing and DNA detection in cervical
specimens. Efficacy in the overall trial populations was consistently lower than among the HPV-naïve population (those without baseline HPV
infection), as presented below. This reflects the fact that many trial participants were already sexually active and previously infected with vaccine HPV
types and highlights the importance of vaccination prior to the onset of sexual activity to maximize effectiveness. (See 'Optimal timing' above.)
● Quadrivalent HPV vaccine – Two large, randomized, double-blind trials compared quadrivalent HPV vaccine with placebo among more than
17,000 females aged 15 to 26 [55,61]. After three years, the efficacy of quadrivalent HPV vaccine for preventing CIN2 or more severe disease due
to HPV vaccine types was:
• 97 to 100 percent among HPV-naïve populations
• 44 percent among the overall population
Efficacy for preventing VIN2 or 3 and VaIN2 or 3 was similarly 100 percent among HPV-naïve populations and 62 percent among the overall
population [55].
● 9-valent HPV vaccine – An international randomized trial compared the 9-valent vaccine with quadrivalent vaccine in approximately 14,000
females aged 16 to 26 years [62]. The efficacy of the 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 (the types not contained in the quadrivalent vaccine) was:
• 97 percent among the HPV-naïve population
In the overall population of study participants, 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 – Two large randomized trials compared bivalent HPV vaccine with placebo or a non-HPV comparator vaccine in females
aged 15 to 25 years [63,64]. Vaccine efficacy was high in HPV-naïve populations in both of these trials. As an example, in one of the trials, which
included nearly 16,000 females, efficacy in preventing CIN2 or more severe disease due to HPV vaccine types was:
• 93 percent among the HPV-naïve population
• 53 percent among the overall population
HPV vaccination also appears to be safe and effective in preventing subsequent infection and cervical disease in older women, but the overall benefit
is less than in younger females [20,21,65]. 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 84 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 22 percent overall [20,21]. Among those who did not have a prior
history of HPV infection and received three doses of vaccine, vaccine efficacy was 91 percent.
Data collected outside the clinical trial setting are also favorable, demonstrating decreased prevalence of HPV-related cervical disease following
introduction of HPV vaccines into national immunization programs [66-72]. As an example, the 2007 implementation of a national program to
administer the quadrivalent vaccine to women aged 12 to 26 years in Australia led to high rates of vaccine coverage, particularly among females under
18 years of age. In one study of the cervical cytology registry in Victoria, Australia, there was a progressive decrease in the incidence of high-grade
cervical squamous intraepithelial lesions among girls 18 years of age or younger in the two years after the vaccination program compared with the four
years preceding it [66]. Reductions in cervical disease have also been observed where vaccine uptake has been suboptimal. As an example, in a study
from New Mexico in the United States, where vaccine uptake ranged from 17 to 40 percent, the incidence of CIN continually decreased among females
aged 15 to 19 years between 2007 and 2014 (10 and 40 percent reduction annually for CIN2 and CIN3, respectively) [72]. Although many of these
studies did not formally link individual vaccination status or implicated HPV type with disease occurrence, they suggest an association between
widespread vaccination and population decreases in HPV-related disease that is consistent with the efficacy observed in clinical trials of the HPV
vaccines and that may reflect vaccine-associated herd immunity.
All licensing trials and most observational data on HPV vaccination describe results with an intended three-dose series. Results with fewer than three
doses are discussed elsewhere. (See 'Immunization schedule' above.)
Anal disease — Data informing the impact of HPV vaccine on anal intraepithelial neoplasia (AIN) and anal cancers are more limited than that for
cervical disease but suggest efficacy in males and expected efficacy in females.
In a planned sub-study of 602 men who have sex with men aged 16 to 26 who participated in a large placebo-controlled trial of the quadrivalent
vaccine, efficacy in preventing AIN secondary to the relevant HPV vaccine types was 78 percent among HPV-naïve males and 50 percent in the overall
population [73].
Among females, there are no direct efficacy data regarding prevention of AIN, but bivalent HPV vaccination has been demonstrated to reduce the
incidence of anal infection with HPV types 16 and 18 [74]. Since the majority of anal cancers in both females and males are related to HPV 16 and
HPV 18, a beneficial impact of vaccination on AIN and anal cancer risk in females is anticipated [74].
Oral disease — Data informing the impact of HPV vaccine on oral disease are limited to studies demonstrating a reduction in oral HPV infection
following vaccination [75,76]. As an example, in a trial originally designed to evaluate bivalent HPV 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)
[75]. Vaccine efficacy for the prevention of oral HPV infection was estimated to be 93 percent. Whether HPV vaccination can prevent the development
of HPV-related oropharyngeal cancer has not yet been evaluated.
Anogenital warts — Clinical trials in females and males have demonstrated the efficacy of quadrivalent HPV vaccine for preventing anogenital
warts (condylomata acuminata) which are most often caused by HPV types 6 and 11. Because 9-valent vaccine also targets these HPV types, it is
expected to have similar efficacy. The bivalent HPV vaccine does not target these HPV types and thus does not prevent anogenital warts.
In a large randomized trial among females aged 16 to 24 years, quadrivalent HPV vaccine efficacy for preventing vulvar and vaginal condylomata was
100 percent among HPV-naïve participants (without evidence of HPV vaccine types at enrollment) and 70 to 78 percent among the overall population
(with or without HPV infection at enrollment) [55]. Similarly, in a placebo-controlled randomized trial among over 4000 males aged 16 to 26,
quadrivalent HPV vaccine efficacy for preventing external genital warts was 90 percent among HPV-naïve participants and 66 percent among the
overall populations [73].
Observational studies have also suggested that quadrivalent HPV vaccination prevents anogenital warts [77-81]. As an example, in a study of nearly
400,000 females born between 1989 and 1999 in Denmark, quadrivalent HPV vaccination was associated with a substantially lower risk of developing
genital warts (229 cases among 248,403 vaccinated versus 2241 cases among 151,367 unvaccinated individuals after an average of 3.5 years of
follow-up) [80]. Declines in the incidence of anogenital warts have also been temporally associated with vaccine availability in both young women and
men in various countries, including Australia [78,79] and the United States [81,82].
Other HPV-associated disease — Human papillomavirus (HPV) vaccination might impact the burden of recurrent respiratory papillomatosis, a
benign but morbid laryngeal tumor in children thought to be caused by HPV (typically types 6 and 11) acquired during passage through the birth canal
of an infected mother. In a study from Australia, the incidence of recurrent respiratory papillomatosis decreased from 0.16 to 0.02 cases per 100,000
children between five and nine years of age following introduction of a national quadrivalent HPV vaccination program among females [83]. All cases
occurred in offspring of unvaccinated females.
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 at least 10 years following vaccination
among female trial participants [84-86]. Persistent antibody levels and protection against HPV infection have also been reported up to 10 years
following vaccination [87-90]. 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 [91]. All HPV vaccines have documented safety in large clinical trials, and
extensive post-licensure data (following approval and clinical use) on the quadrivalent vaccine support this safety profile.
In light of the growing data on the safety of the HPV vaccine, the World Health Organization (WHO) Global Advisory Committee on Vaccine Safety
stated that the benefit-risk profile remains favorable [92]. Additionally, it warned against claims of harm that are raised on the basis of anecdotal reports
in the absence of biological or epidemiological substantiation.
Quadrivalent vaccine (Gardasil) — Data from both registration trials and post-licensure safety surveillance systems demonstrate that the vaccine is
safe and well tolerated apart from mild injection site reactions. Postvaccination syncopal events have emerged as a potential serious adverse effect,
although it does not appear unique to HPV vaccination, since syncope after vaccination occurs with other vaccines administered to adolescents
[93,94]. A waiting time after vaccination is recommended to try to reduce the likelihood of injury from possible syncope. (See 'Postvaccination
instructions' above.)
In the large licensing trials, the safety profile of the quadrivalent vaccine was evaluated in diverse populations of females from both resource-rich and
resource-limited settings [55,61]. Mild injection site reactions were the most commonly observed adverse events in these studies as well as in trials in
males [73].
Subsequently, surveillance systems and observational studies of vaccinated populations have supported the safety of quadrivalent vaccination []. As an
example, in the United States, reports of adverse events to the Vaccine Adverse Event Reporting System (VAERS) have been consistent with the pre-
licensure data [93,95]. Between June 2006 and March 2013, approximately 57 million doses of quadrivalent HPV vaccines were distributed in the
United States. Over this time, VAERS received 21,194 reports of adverse events following HPV immunization among females; the vast majority (92
percent) were considered mild [95]. Among serious events, headache, nausea, vomiting, fatigue, dizziness, syncope, and generalized weakness were
the most frequently reported. There was no increased risk of Guillain-Barré Syndrome compared with other vaccines in similar age groups [93].
There does appear to be an increased risk of syncope with the quadrivalent vaccine, but whether this is unique to this vaccine is unclear. In the United
States, a disproportionate number of syncopal events following quadrivalent vaccine administration had been reported to the VAERS [93]. 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
health care system who received at least one vaccine dose, emergency department visits or hospitalizations were higher during the postvaccine period
compared with a subsequent control period for 10 of 265 diagnostic categories evaluated, including viral, bacterial, and skin infections and congenital
anomalies [96]. 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. The incidence of
syncope among adolescents has increased overall with the introduction of other routine immunizations as well, such as meningococcal vaccine
[93,94].
Other adverse events that initially appeared to be vaccine related have not been substantiated by further study. Although venous thromboembolism
(VTE) rates reported to the VAERS in the United States 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) [93]. 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) [97]. 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 [98].
Anaphylaxis had also been reported following administration of the quadrivalent vaccine [93,99], 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 [99]. However,
some of those cases were subsequently thought not to have represented anaphylaxis and other studies from Australia did not confirm this high rate
[100,101]. In the United States VAERS surveillance system, only 10 cases met predefined criteria for anaphylaxis; the overall risk ratio was 0.1 case
per 100,000 doses distributed [93]. (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 [102].
9-valent vaccine (Gardasil 9) — Fewer post-licensure safety data are available for the 9-valent vaccine than the quadrivalent vaccine. The overall
safety profile appears similar, although the frequency of mild local reactions might be higher with the 9-valent vaccine. (See 'Quadrivalent vaccine
(Gardasil)' above.)
In an analysis of seven trials in which over 15,000 individuals received at least one dose of the 9-valent vaccine, the most common adverse effects
were mild or moderate injection site reactions (pain, erythema, and swelling) [103]. These occurred slightly more often than with the quadrivalent
vaccine. The frequency of systemic adverse effects (eg, headache, fever, nausea, dizziness) was similar with the 9-valent and quadrivalent vaccines.
Serious adverse effects occurred in <0.1 percent.
Bivalent vaccine (Cervarix) — Data from large placebo-controlled randomized trials indicate that bivalent HPV vaccine is safe. As an example, in one
trial of more than 18,000 females aged 15 to 25 years, there were no differences in serious adverse events between vaccine and placebo recipients.
Post-licensure data are sparse from the United States, where almost all HPV vaccine used through 2015 was quadrivalent vaccine. In the United
States, there were 52 reports to VAERS of adverse events following administration of bivalent vaccine through September 2011, and 98 percent were
considered nonserious.
Behavioral impact — Some surveys of parents of adolescent girls identified a concern for sexual disinhibition following HPV vaccine receipt,
particularly among older and ethnic minority parents [104,105]. Studies have not supported an increase in risky sexual behavior following vaccination
[106-108]. In a retrospective study of preteenage girls enrolled in a large health care 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 [106]. After adjustment for baseline health care 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. 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 [109-111]. In the
United States, uptake of HPV vaccination has been suboptimal [112,113]. In 2015, based on results of a national survey among adolescents who had
provider-reported vaccination records, estimated vaccine coverage among females and males aged 13 to 17 was 63 and 50 percent for at least one
dose and only 42 and 28 percent for at least three doses (at a time when three doses was the recommended schedule for all recipients) [112]. In an
earlier 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 [95]. This highlights a lack of understanding about the rationale for HPV vaccination on the part of the parent and the important role of the
health care 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 [95]. 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 [114]. 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 complete-dose HPV vaccination coverage (with either
bivalent or quadrivalent vaccine) to 80 percent in females, approximately 53,000 additional cases of cervical cancer could be prevented in the United
States over the lifetimes of those currently aged ≤12 years [115]. More cervical cancers would conceivably be prevented with similar coverage with the
9-valent vaccine.
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 [116].
IMPORTANCE OF CANCER SCREENING
Cervical screening — Clinicians should be aware that HPV immunization is not effective in clearing HPV infection, genital warts, or cervical
intraepithelial neoplasia that is already present, and the vaccine does not protect against 100 percent of types known to cause cervical cancer. Thus,
HPV vaccination status does not impact cervical cancer screening recommendations. In the United States, cervical cancer screening is recommended
for all females beginning at age 21 (table 1). A preventive health care visit is an opportune time to discuss and offer HPV vaccination and/or cervical
screening depending on the age of the woman [117]. Detailed information regarding screening for cervical cancer is found elsewhere. (See "Screening
for cervical 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 and new screening guidelines issued, 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-infected males and females and other populations known to be at increased risk of anal cancer. (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'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are
provided separately. (See "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Immunizations in adults"
and "Society guideline links: Cervical cancer".)
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 5th to 6th 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 10th to 12th 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 education: Human papillomavirus (HPV) vaccine (The Basics)" and "Patient education: Anogenital warts (The Basics)"
and "Patient education: Pap tests (The Basics)" and "Patient education: Vaccines for children age 7 to 18 years (The Basics)")
● Beyond the Basics topics (see "Patient education: Human papillomavirus (HPV) vaccine (Beyond the Basics)" and "Patient education: Genital
warts in women (Beyond the Basics)" and "Patient education: Cervical cancer screening (Beyond the Basics)" and "Patient education: Vaccines for
children age 7 to 18 years (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Three human papillomavirus (HPV) vaccines have been clinically developed, although not all are available in all locations:
• Quadrivalent vaccine (Gardasil) targets HPV types 6, 11, 16, and 18.
• 9-valent vaccine (Gardasil 9) targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
• Bivalent vaccine (Cervarix) targets HPV types 16 and 18.
In the United States, only the 9-valent vaccine has been available since the end of 2016. (See 'Available vaccines' above.)
● Vaccination with 9-valent, quadrivalent, or bivalent HPV vaccine provides a direct benefit to female and male recipients by safely protecting against
cancers that can result from persistent high-risk HPV infection. HPV types 16 and 18 cause approximately 70 percent of all cervical cancers
worldwide and nearly 90 percent of anal cancers, as well as a significant proportion of oropharyngeal cancer, vulvar and vaginal cancer, and penile
cancer. Quadrivalent and 9-valent vaccine also protect against anogenital warts, 90 percent of which are caused by HPV types 6 and 11. Although
the burden of HPV-associated disease is lower in males than females and thus the direct absolute benefit to males is smaller, the indirect benefit
to males from vaccinating females only is incomplete and vaccinating males provides additional population benefits from herd immunity. (See
'Rationale' above.)
● In accordance with the Advisory Committee on Immunization Practices (ACIP) in the United States, we recommend routine HPV vaccination for
females (Grade 1A) and males (Grade 1B). The recommended age ranges for administration are as follows:
• For females – Routine immunization should be offered at 11 to 12 years of age, but can be administered starting at 9 years. Catch-up
vaccination should be offered for females aged 13 to 26 years who have not been previously vaccinated.
• For males – Routine immunization should be offered at 11 to 12 years of age, but can be administered starting at 9 years. Catch-up
vaccination should be offered for males between the ages of 13 to 21 who have not been previously vaccinated. For men who have sex with
men (MSM) and immunocompromised males, catch-up vaccination should be offered up to age 26.
Within the recommended age range, the optimal time for HPV immunization is prior to an individual's sexual debut. HPV vaccination is also
reasonable for older individuals who have a low risk of prior HPV exposure (eg, no prior sexual experience or certain lifelong sexual monogamy)
but are at risk for future exposure. (See 'Indications and age range' above and 'Optimal timing' above.)
● If cost and availability are not issues, we recommend the 9-valent HPV vaccine rather than other HPV vaccines (Grade 1B). For individuals
starting any HPV vaccine series when they are younger than 15 years old, we suggest administering a two- rather than a three-dose vaccine
series (Grade 2C). In such patients, the two doses are administered at least six months apart. For individuals starting any HPV vaccine series at
15 years and older, the HPV vaccine is administered in three doses at 0, at 1 to 2 months, and at 6 months. Immunocompromised patients should
also receive a three-dose series. (See 'Immunization schedule' above.)
● HPV vaccination during pregnancy is typically avoided because of limited information about safety; however, data from inadvertent use in this
setting are increasingly available and reassuring. (See 'Pregnant or breastfeeding females' above.)
● Excellent antibody responses have been reported following immunization with the 9-valent, quadrivalent, and bivalent vaccines, with
seroconversion rates of 93 to 100 percent in females and 99 to 100 percent in males. Elicited titers are generally higher in younger than in older
individuals. (See 'Immunogenicity' above.)
● Multicenter, double-blind, placebo-controlled trials have demonstrated the 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 HPV vaccines have also demonstrated high efficacy against vaccine type-associated vaginal and vulvar intraepithelial neoplasia. They have
demonstrated efficacy against genital warts associated with HPV 6 and HPV 11. Reduction in anal intraepithelial neoplasia in MSM, anal HPV
infection in females, and oral HPV infection in females has also been demonstrated in trials. (See 'Efficacy' above.)
● Data from both registration trials and post-licensure safety surveillance systems demonstrate that the vaccine is safe and well tolerated apart from
mild injection site reactions. Postvaccination syncopal events have emerged as a potential serious adverse effect, although it does not appear
unique to HPV vaccination. (See 'Vaccine safety' above.)
● Clinicians should be aware that HPV immunization is not effective in clearing HPV infection, genital warts, or anogenital intraepithelial neoplasia
that is already present. HPV vaccination status does not impact cervical cancer screening recommendations. (See 'Importance of cancer
screening' above and "Screening for cervical cancer".)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Philip Castle, PhD, MPH, who contributed to an earlier version of
this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. 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; 386:2078.
2. Sanders GD, Taira AV. Cost-effectiveness of a potential vaccine for human papillomavirus. Emerg Infect Dis 2003; 9:37.
3. 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.
4. Kulasingam SL, Myers ER. Potential health and economic impact of adding a human papillomavirus vaccine to screening programs. JAMA 2003;
290:781.
5. Chesson HW, et al. Cost effectiveness models of HPV vaccines. May 9, 2006 - 2006 National STD Prevention Conference.
6. Westra TA, Rozenbaum MH, Rogoza RM, et al. Until which age should women be vaccinated against HPV infection? Recommendation based on
cost-effectiveness analyses. J Infect Dis 2011; 204:377.
7. Drolet M, Bénard É, Boily MC, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a
systematic review and meta-analysis. Lancet Infect Dis 2015; 15:565.
8. Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med 2008; 359:821.
9. 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.
10. Chesson HW, Ekwueme DU, Saraiya M, et al. The cost-effectiveness of male HPV vaccination in the United States. Vaccine 2011; 29:8443.
11. Hughes JP, Garnett GP, Koutsky L. The theoretical population-level impact of a prophylactic human papilloma virus vaccine. Epidemiology 2002;
13:631.
12. Taira AV, Neukermans CP, Sanders GD. Evaluating human papillomavirus vaccination programs. Emerg Infect Dis 2004; 10:1915.
13. 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.
14. Elfström KM, Lazzarato F, Franceschi S, et al. Human Papillomavirus Vaccination of Boys and Extended Catch-up Vaccination: Effects on the
Resilience of Programs. J Infect Dis 2016; 213:199.
15. Newall AT, Beutels P, Wood JG, et al. Cost-effectiveness analyses of human papillomavirus vaccination. Lancet Infect Dis 2007; 7:289.
16. Kim DK, Riley LE, Hunter P. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or
Older - United States, 2018. MMWR Morb Mortal Wkly Rep 2018; 67:158.
17. 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.
18. 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.
19. Robinson CL, Romero JR, Kempe A, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children
and Adolescents Aged 18 Years or Younger - United States, 2018. MMWR Morb Mortal Wkly Rep 2018; 67:156.
20. Wheeler CM, Skinner SR, Del Rosario-Raymundo MR, et al. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-
adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet
Infect Dis 2016; 16:1154.
21. 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.
22. Castellsagué X, Muñoz N, Pitisuttithum P, et al. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18)
recombinant vaccine in adult women 24-45 years of age. Br J Cancer 2011; 105:28.
23. Luna J, Plata M, Gonzalez M, et al. Long-term follow-up observation of the safety, immunogenicity, and effectiveness of Gardasil™ in adult
women. PLoS One 2013; 8:e83431.
24. Immunization Expert Work Group, Committee on Adolescent Health Care. Committee Opinion No. 704: Human Papillomavirus Vaccination.
Obstet Gynecol 2017; 129:e173.
25. American Academy of Family Physicians. Human papillomavirus vaccine (HPV). www.aafp.org/patient-care/public-health/immunizations/disease-
population/hpv.html#Recommendations (Accessed on June 05, 2017).
26. American Academy of Pediatrics. Human Papillomaviruses. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th edition, Ki
mberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.576.
27. Saslow D, Andrews KS, Manassaram-Baptiste D, et al. Human papillomavirus vaccination guideline update: American Cancer Society guideline
endorsement. CA Cancer J Clin 2016; 66:375.
28. International Papillomavirus Society (IPVS). http://ipvsoc.org/ (Accessed on June 05, 2017).
29. Arrossi S, Temin S, Garland S, et al. Primary prevention of cervical cancer: American Society of Clinical Oncology resource-stratified guideline. M
arch 17, 2017. http://www.asco.org/practice-guidelines/quality-guidelines/guidelines/resource-stratified?et_cid=39041084&et_rid=463563306&link
id=http%3A//www.asco.org/rs-cervical-cancer-primary-prev-guideline#/24681 (Accessed on March 17, 2017).
30. Human papillomavirus vaccines: WHO position paper, May 2017 http://apps.who.int/iris/bitstream/10665/255353/1/WER9219.pdf?ua=1.
31. 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).
32. 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.
33. 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.
34. 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.
35. Sankaranarayanan R, Prabhu PR, Pawlita M, et al. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV
vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol 2016; 17:67.
36. Puthanakit T, Huang LM, Chiu CH, et al. Randomized Open Trial Comparing 2-Dose Regimens of the Human Papillomavirus 16/18 AS04-
Adjuvanted Vaccine in Girls Aged 9-14 Years Versus a 3-Dose Regimen in Women Aged 15-25 Years. J Infect Dis 2016; 214:525.
37. Iversen OE, Miranda MJ, Ulied A, et al. Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose
Regimen in Women. JAMA 2016; 316:2411.
38. Ogilvie G, Sauvageau C, Dionne M, et al. Immunogenicity of 2 vs 3 Doses of the Quadrivalent Human Papillomavirus Vaccine in Girls Aged 9 to
13 Years After 60 Months. JAMA 2017; 317:1687.
39. 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.
40. 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.
41. 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.
42. 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.
43. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis
2014; 58:309.
44. 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.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. Gardasil 9 (Human papillomavirus 9-valent vaccine, recombinant. US FDA approved product information; Whitehouse Station, NJ: Merck & Co, In
c. December 2014.
51. 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.
52. 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.
53. 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.
54. 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.
55. 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.
56. Van Damme P, Olsson SE, Block S, et al. Immunogenicity and Safety of a 9-Valent HPV Vaccine. Pediatrics 2015; 136:e28.
57. Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant Vaccines and Related Biological Products Advisory Committee (VRBPA
C) Briefing Document, September 9, 2009. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandO
therBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181371.pdf (Accessed on February 12, 2013).
58. 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.
59. 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.
60. 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.
61. FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;
356:1915.
62. 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.
63. 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.
64. Hildesheim A, Wacholder S, Catteau G, et al. Efficacy of the HPV-16/18 vaccine: final according to protocol results from the blinded phase of the
randomized Costa Rica HPV-16/18 vaccine trial. Vaccine 2014; 32:5087.
65. Castle PE, Schmeler KM. HPV vaccination: for women of all ages? Lancet 2014; 384:2178.
66. Brotherton JM, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an
ecological study. Lancet 2011; 377:2085.
67. Crowe E, Pandeya N, Brotherton JM, et al. Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical
abnormalities: case-control study nested within a population based screening programme in Australia. BMJ 2014; 348:g1458.
68. Baldur-Felskov B, Dehlendorff C, Munk C, Kjaer SK. Early impact of human papillomavirus vaccination on cervical neoplasia--nationwide follow-
up of young Danish women. J Natl Cancer Inst 2014; 106:djt460.
69. Smith LM, Strumpf EC, Kaufman JS, et al. The early benefits of human papillomavirus vaccination on cervical dysplasia and anogenital warts.
Pediatrics 2015; 135:e1131.
70. Hofstetter AM, Ompad DC, Stockwell MS, et al. Human Papillomavirus Vaccination and Cervical Cytology Outcomes Among Urban Low-Income
Minority Females. JAMA Pediatr 2016; 170:445.
71. Garland SM, Kjaer SK, Muñoz N, et al. Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10
Years of Real-world Experience. Clin Infect Dis 2016; 63:519.
72. Benard VB, Castle PE, Jenison SA, et al. Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus
Vaccine Era. JAMA Oncol 2016.
73. 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.
74. 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.
75. 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.
76. Chaturvedi AK, Graubard BI, Broutian T, et al. Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among
Young Adults in the United States. J Clin Oncol 2018; 36:262.
77. Tabrizi SN, Brotherton JM, Kaldor JM, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012;
206:1645.
78. Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national
sentinel surveillance data. Lancet Infect Dis 2011; 11:39.
79. Read TR, Hocking JS, Chen MY, et al. The near disappearance of genital warts in young women 4 years after commencing a national human
papillomavirus (HPV) vaccination programme. Sex Transm Infect 2011; 87:544.
80. Blomberg M, Dehlendorff C, Munk C, Kjaer SK. Strongly decreased risk of genital warts after vaccination against human papillomavirus:
nationwide follow-up of vaccinated and unvaccinated girls in Denmark. Clin Infect Dis 2013; 57:929.
81. Bauer HM, Wright G, Chow J. Evidence of human papillomavirus vaccine effectiveness in reducing genital warts: an analysis of California public
family planning administrative claims data, 2007-2010. Am J Public Health 2012; 102:833.
82. Flagg EW, Schwartz R, Weinstock H. Prevalence of anogenital warts among participants in private health plans in the United States, 2003-2010:
potential impact of human papillomavirus vaccination. Am J Public Health 2013; 103:1428.
83. Novakovic D, Cheng ATL, Zurynski Y, et al. A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After
Implementation of a National HPV Vaccination Program. J Infect Dis 2018; 217:208.
84. Lehtinen M, Paavonen J, Wheeler CM, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical
intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 2012; 13:89.
85. Huh WK, Joura EA, Giuliano AR, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in
women aged 16-26 years: a randomised, double-blind trial. Lancet 2017; 390:2143.
86. Kjaer SK, Nygård M, Dillner J, et al. A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human Papillomavirus Vaccine in 4
Nordic Countries. Clin Infect Dis 2018; 66:339.
87. 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.
88. 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.
89. Ferris D, Samakoses R, Block SL, et al. Long-term study of a quadrivalent human papillomavirus vaccine. Pediatrics 2014; 134:e657.
90. Toh ZQ, Russell FM, Reyburn R, et al. Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus
(HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.
Clin Infect Dis 2017; 64:852.
91. 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.
92. World Health Organization. Global Advisory Committee on Vaccine Safety statement on the continued safety of HPV vaccination. March 12, 201
4. http://www.who.int/vaccine_safety/committee/topics/hpv/GACVS_Statement_HPV_12_Mar_2014.pdf (Accessed on September 04, 2014).
93. Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA 2009;
302:750.
94. Centers for Disease Control and Prevention (CDC). Syncope after vaccination--United States, January 2005-July 2007. MMWR Morb Mortal Wkly
Rep 2008; 57:457.
95. Human Papillomavirus Vaccination Coverage Among Adolescent Girls, 2007–2012, and Postlicensure Vaccine Safety Monitoring, 2006–2013 —
United States. MMWR Recomm Rep 2013; 62:591.
96. 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.
97. 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.
98. Scheller NM, Pasternak B, Svanström H, Hviid A. Quadrivalent human papillomavirus vaccine and the risk of venous thromboembolism. JAMA
2014; 312:187.
99. Brotherton JM, Gold MS, Kemp AS, et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ 2008; 179:525.
100. Douglas RJ. Anaphylaxis following quadrivalent human papillomavirus vaccination - even safer than it appears. CMAJ 2008.
101. Kang LW, Crawford N, Tang ML, et al. Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort
study. BMJ 2008; 337:a2642.
102. 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.
103. Moreira ED Jr, Block SL, Ferris D, et al. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics
2016; 138.
104. Schuler CL, Reiter PL, Smith JS, Brewer NT. Human papillomavirus vaccine and behavioural disinhibition. Sex Transm Infect 2011; 87:349.
105. Marlow LA, Forster AS, Wardle J, Waller J. Mothers' and adolescents' beliefs about risk compensation following HPV vaccination. J Adolesc
Health 2009; 44:446.
106. 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.
107. 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.
108. Jena AB, Goldman DP, Seabury SA. Incidence of sexually transmitted infections after human papillomavirus vaccination among adolescent
females. JAMA Intern Med 2015; 175:617.
109. National HPV vaccination program register. Coverage Data. Australia. http://www.hpvregister.org.au/research/coverage-data (Accessed on July 2
0, 2015).
110. Vaccine uptake guidance and the latest coverage data. Public Health England. https://www.gov.uk/government/collections/vaccine-uptake (Acces
sed on July 20, 2015).
111. 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.
112. Jeyarajah J, Elam-Evans LD, Stokley S, et al. Human Papillomavirus Vaccination Coverage Among Girls Before 13 Years: A Birth Year Cohort
Analysis of the National Immunization Survey-Teen, 2008-2013. Clin Pediatr (Phila) 2016; 55:904.
113. Walker TY, Elam-Evans LD, Singleton JA, et al. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents
Aged 13-17 Years - United States, 2016. MMWR Morb Mortal Wkly Rep 2017; 66:874.
114. 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.
115. Chesson HW, Ekwueme DU, Saraiya M, et al. The estimated impact of human papillomavirus vaccine coverage on the lifetime cervical cancer
burden among girls currently aged 12 years and younger in the United States. Sex Transm Dis 2014; 41:656.
116. Niccolai LM, Hansen CE. Practice- and Community-Based Interventions to Increase Human Papillomavirus Vaccine Coverage: A Systematic
Review. JAMA Pediatr 2015; 169:686.
117. 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.
Topic 8325 Version 63.0
GRAPHICS
Cervical cancer screening recommendations from United States professional organizations*
Recommended screening test and Post-

Age to frequency hysterectomy HPV
Organization Age to initiate
discontinue for benign vaccination
Age 21 to 29 Age ≥30 disease
¶ Δ
ACS/ASCCP/ASCP 21 65 Pap test every three Co-testing (pap test Not indicated ◊ Same
(2012) years (preferred) and HPV recommendations as
testing) every five unvaccinated women
years (preferred)
Pap test every three

years
ASCCP/SGO (2015 21 N/A Can consider primary Can consider primary N/A N/A
interim guidelines) HPV testing every HPV testing every
three years for three years
women age ≥25
USPSTF (2012) 21 65 § Pap test every three Pap test every three Not indicated ‡ Same
years years recommendations as
unvaccinated women
Alternative: Co-
testing (pap test and
HPV testing) every
five years ¥
ACOG (2016) 21 65 † Pap test every three Co-testing (pap test Not indicated** Same
years and recommendations as
HPV testing) every unvaccinated women
five years (preferred)
Can consider primary Pap test every three

HPV testing every years
three years for
Can consider primary
women age ≥25
HPV testing every
three years for
women age ≥25
ACP (2015) 21 65 § Pap test every three Pap test every three Not indicated ‡ N/A
years years
Alternative: Co-
testing (pap test and
HPV testing) every
five years ¥
HPV: human papillomavirus; ACS: American Cancer Society; ASCCP: American Society for Colposcopy and Cervical Pathology; ASCP: American Society for Clinical
Pathology; SGO: Society of Gynecologic Oncology; USPSTF: United States Preventive Services Task Force; ACOG: American College of Obstetricians and Gynecologists;
ACP: American College of Physicians; DES: diethylstilbestrol; HIV: human immunodeficiency virus; CIN: cervical intraepithelial neoplasia.
* These guidelines are intended for the general population and are not intended for women who have a history of cervical cancer, high-grade cervical precancers, DES in
utero exposure, or who are immunocompromised, as with HIV infection.
¶ Regardless of the age of sexual initiation or other risk factors.
Δ For women with evidence of adequate negative prior screening (three consecutive negative cytology results or two consecutive negative co-tests with the previous 10
years, with the most recent test within the previous 5 years) and no history of CIN 2 or greater within the last 20 years. Screening should not be resumed for any reason,
even if a woman has a new sexual partner.
◊ For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2, CIN 3 in the past 20 years, or a history of cervical
cancer ever. Evidence of adequate negative prior screening not required.
§ For women with evidence of adequate negative prior screening, specified as three consecutive negative cytology results or two consecutive negative co-tests within the
previous 10 years, with the most recent test within the previous 5 years.
¥ For women who want to lengthen the screening interval.
‡ For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2 or higher.
† For women with no history of CIN 2 or higher with evidence of prior adequate screening (three or more negative cytology test results in a row or two consecutive
negative co-tests in the past 10 years, with the most recent within the past 5 years).
** For women who have had a benign hysterectomy with removal of the cervix who do not have a history of CIN 2, CIN 3, or cervical cancer. Women in whom a negative
history cannot be documented should continue to be screened.
1. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical
Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62:147.
2. Moyer VA. Screening for cervical cancer: United States Preventive Services Task Force recommendation statement. Ann Intern Med 2012; 156:880.
3. Cervical cytology screening. ACOG Practice Bulletin No. 157. American College of Obstetricians and Gynecologists. Obstet Gynecol 2016; 127:e1
4. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol
2015; 136:178. http://dx.doi.org/10.1016/j.ygyno.2014.12.022
5. Sawaya GF, Kulasingam S, Denberg TD, et al. Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of
the American College of Physicians. Ann Intern Med 2015; 162:851.
Graphic 82951 Version 15.0
Contributor Disclosures
J Thomas Cox, MD Speaker's Bureau: Roche [HPV testing (Cobas HPV test)]. Joel M Palefsky, MD Grant/Research/Clinical Trial Support: Merck
and Co [HPV vaccine (Gardasil-9)]. Consultant/Advisory Boards: Antiva Therapeutics [HPV therapeutics]; Agenovir Corporation [HPV therapeutics].
Equity Ownership/Stock Options: Antiva Therapeutics [HPV therapeutics]; Agenovir Corporation [HPV therapeutics]; Ubiome [HPV diagnostics]. 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

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9/4/2018 Human papillomavirus vaccination - UpToDate

Official reprint from UpToDate®

Human papillomavirus vaccination

Authors: J Thomas Cox, MD, Joel M Palefsky, MD

● Bivalent vaccine (Cervarix) targets HPV types 16 and 18.

Dosing and administration is discussed elsewhere. (See 'Administration' below.)

EFFICACY AND IMMUNOGENICITY

• 97 to 100 percent among HPV-naïve populations

• 44 percent among the overall population

• 97 percent among the HPV-naïve population

• 93 percent among the HPV-naïve population

• 53 percent among the overall population

IMPORTANCE OF CANCER SCREENING

SUMMARY AND RECOMMENDATIONS

• Bivalent vaccine (Cervarix) targets HPV types 16 and 18.

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

Topic 8325 Version 63.0

Cervical cancer screening recommendations from United States professional organizations*

Recommended screening test and Post-

Pap test every three

Can consider primary Pap test every three

Graphic 82951 Version 15.0

Conflict of interest policy

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