Female Human Papillomavirus Vaccination Research Articles

Clinical and economic impact of school-based nonavalent human papillomavirus vaccination in females in Malaysia.

Clinical and economic impact of school-based nonavalent human papillomavirus vaccination in females in Malaysia.

Public health impact of 2-, 4-, and 9-valent HPV vaccination in females on cervical and noncervical diseases in men and women under different coverage scenarios in China: A simulation study

ABSTRACT The high prevalence of human papillomavirus (HPV) infection in China suggests there would be a substantial positive health impact of widespread vaccination against HPV. We adapted a previously described dynamic transmission model of the natural history of HPV infection and related diseases to the Chinese setting to estimate the public health impact in China of 2-valent (with and without cross-protection), 4-valent, and 9-valent HPV vaccination strategies. The model predicted the incidence and mortality associated with HPV-related diseases, including cervical and noncervical cancers, genital warts, and recurrent respiratory papillomatosis (RRP), based on the various vaccination coverage rate (VCR) scenarios, over a 100-year time horizon. The public health impact of the 4 vaccination strategies was estimated in terms of cases and deaths averted compared to a scenario with no vaccination. Under the assumption of various primary and catch-up VCR scenarios, all 4 vaccination strategies reduced the incidence of cervical cancer in females and noncervical cancers in both sexes, and the 4-valent and 9-valent vaccines reduced the incidence of genital warts and RRP in both sexes. The 9-valent vaccination strategy was superior on all outcomes. The number of cervical cancer cases averted over 100 years ranged from ~ 1 million to ~ 5 million while the number of cervical cancer deaths averted was ~ 345,000 to ~ 1.9 million cases, depending on the VCR scenario. The VCR for primary vaccination was the major driver of cases averted.

Significant Declines in Juvenile-onset Recurrent Respiratory Papillomatosis Following Human Papillomavirus (HPV) Vaccine Introduction in the United States.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare and serious disease caused by human papillomavirus (HPV) presumably acquired during vaginal delivery. HPV vaccination of females through age 26 years, recommended in the United States since 2006, can prevent HPV transmission. We assessed trends in JORRP cases before and after HPV vaccine introduction in the United States. Case-patients were identified from 26 pediatric otolaryngology centers in 23 U.S. states. Demographics and clinical history were abstracted from medical records. Case-patients were grouped by year of birth, and birth-cohort incidences were calculated using number of births from either national or state-level natality data from the 23 states. We calculated incidence rate ratios (IRR) and 95% confidence intervals (CI) in 2-year intervals. We identified 576 U.S. JORRP case-patients born in 2004-2013. Median age at diagnosis was 3.4 years (interquartile range: 1.9, 5.5). Number of identified JORRP case-patients declined from a baseline of 165 born in 2004-2005 to 36 born in 2012-2013. Incidence of JORRP per 100 000 births using national data declined from 2.0 cases in 2004-2005 to 0.5 cases in 2012-2013 (IRR = 0.2, 95% CI = .1-.4); incidence using state-level data declined from 2.9 cases in 2004-2005 to 0.7 cases in 2012-2013 (IRR = 0.2, 95% CI = .1-.4). Over a decade, numbers of JORRP case-patients and incidences declined significantly. Incidences calculated using national denominator data are likely underestimates; those calculated using state-level denominator data could be overestimates. These declines are most likely due to HPV vaccination. Increasing vaccination uptake could lead to elimination of this HPV-related disease.

Determinants of Human Papillomavirus Vaccine Uptake by Adult Women Attending Cervical Cancer Screening in 9 European Countries

Human papillomavirus-vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated. This was an intervention study. Study participants were women aged 25-45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018. Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination. Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019. Among 3,646 participants, 2,748 (range by country=50%-96%) accepted vaccination, and 2,151 (range=30%-93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%-59%) and the need for more information on human papillomavirus vaccines (range=1%-72%). No safety issues were experienced by vaccinated women. Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings. EudraCT Number 2014-003177-42.

Comparing immunogenicity of the Escherichia coli-produced bivalent human papillomavirus vaccine in females of different ages

BackgroundThe safety and efficacy of a recently licensed Escherichia coli (E. coli)-produced bivalent HPV vaccine have been shown. Specific antibody levels are important indicators to evaluate the efficacy of vaccination. Therefore, we compared the immunogenicity of this HPV 16/18 vaccine in females of different ages in this study. MethodsImmunogenicity of the vaccine was analyzed in the per-protocol sets for immunogenicity (PPS-I) of a phase III trial and an immune-bridging trial. The serum samples were collected at month 0 and one month after the final dose (month 7) to assess the specific IgG antibody levels by ELISA. The seroconversion rates, geometric mean concentration (GMC), and geometric mean increase (GMI) were used to assess the immunogenicity of the test vaccine. The non-linear association of antibody levels with age was estimated via natural cubic splines and the Akaike information criterion was used to assess optimal model. ResultsBy combining the PPS-I data from the two trials, nearly all of the females seroconverted for both HPV types. In the 3-dose group, the GMC of IgG to both HPV types decreased with increasing age, especially in adolescent girls and young women. For HPV-16 and -18, the declining trend slowed down in women older than 32 and 35 years old, respectively. The GMI ranged from 648 to 80 for HPV-16 and from 218 to 42 for HPV-18. In the 2-dose group, the specific antibodies for HPV-16 and -18 peaked in girls aged 10 years with GMIs of 401 and 98, respectively, and then decreased with age. ConclusionsThe E. coli-produced bivalent HPV-16/18 vaccine induced specific antibody responses in females aged 9–45 years. The antibody levels were inversely associated with age, and the declining trends slowed down in women older than 32 or 35 years for HPV-16 and -18, respectively.

Impact and Cost-Effectiveness of Human Papillomavirus Vaccination Campaigns

Data to inform evidence-based policy of human papillomavirus (HPV) vaccine delivery strategies in low- and middle-income countries are limited. We examined the cost-effectiveness of campaign compared with routine delivery strategies of adolescent female HPV vaccination in Uganda. We used a multiple modeling approach that captured HPV transmission, cervical carcinogenesis, and population demographics to project health and economic outcomes associated with HPV vaccination. Costs included vaccination and operational costs and cervical cancer costs over the lifetimes of the current female population in Uganda. Health outcomes included number of cervical cancer cases and disability-adjusted life years (DALY). Incremental cost-effectiveness ratios (i.e., cost per DALY averted) were calculated and compared against gross domestic product (GDP) per capita. Compared with routine HPV vaccination of 9-year-old girls at 70% coverage, campaign vaccination yielded greater health benefits if campaigns occurred frequently and targeted a wide age range. Campaign delivery strategies were both less costly and more effective than routine HPV vaccination. Campaign vaccination of 9- to 30-year-old girls/women at a 3-year frequency (40% coverage) was considered cost-effective compared with the GDP per capita threshold for Uganda ($674 in U.S. 2015 dollars). We projected that campaign HPV vaccination would provide substantial population health benefits compared with routine vaccination. Expanding the target age range of campaign vaccination up to age 30 years may be an efficient strategy, depending on the achievable coverage level and campaign frequency. In settings where routine health systems infrastructure may be limited, reaching adolescent populations with a campaign delivery strategy may be an efficient use of resources.

Estimated Number of Cases of High-Grade Cervical Lesions Diagnosed Among Women - United States, 2008 and 2016.

Human papillomavirus (HPV) causes approximately 30,000 cancers in the United States annually (1). HPV vaccination was introduced in 2006 to prevent HPV-associated cancers and diseases (1). Cervical cancer is the most common HPV-associated cancer in women (1). Whereas HPV-associated cancers typically take decades to develop, screen-detected high-grade cervical lesions (cervical intraepithelial neoplasia grades 2 [CIN2], 3 [CIN3], and adenocarcinoma in situ, collectively CIN2+) develop within a few years after infection and have been used to monitor HPV vaccine impact (1-3). CDC analyzed data from the Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT), a population-based CIN2+ surveillance system, to describe rates of CIN2+ among women aged ≥18 years during 2008-2016. Age-specific rates were applied to U.S. population data to estimate the total number of CIN2+ cases diagnosed in the United States in 2008* and in 2016. From 2008 to 2016, the rate of CIN2+ per 100,000 women declined significantly in women aged 18-19 years and 20-24 years and increased significantly in women aged 40-64 years. In the United States in 2008, an estimated 216,000 (95% confidence interval [CI]=194,000-241,000) CIN2+ cases were diagnosed, 55% of which were in women aged 18-29 years; in 2016, an estimated 196,000 (95% CI = 176,000-221,000) CIN2+ cases were diagnosed, 36% of which were in women aged 18-29 years. During 2008 and 2016, an estimated 76% of CIN2+ cases were attributable to HPV types targeted by the vaccine currently used in the United States. These estimates of CIN2+ cases likely reflect changes in CIN2+ detection resulting from updated cervical cancer screening and management recommendations, as well as primary prevention through HPV vaccination. Increasing coverage of HPV vaccination in females at the routine age of 11 or 12 years and catch-up vaccination through age 26 years will contribute to further reduction in cervical precancers.

Population-Level Herd Protection of Males From a Female Human Papillomavirus Vaccination Program: Evidence from Australian Serosurveillance.

Australia instituted funded female human papillomavirus (HPV) immunization in 2007, followed by a targeted male vaccination program in 2013. To date, Australia is one of only several countries with a funded male HPV immunization program. In 2012-2013, we conducted a survey of HPV seroprevalence in males to assess whether or not a herd impact of female vaccination could be observed. We conducted a cross-sectional study of de-identified residual diagnostic test serum samples from males aged 15-39 years from laboratories in 3 Australian states and calculated the proportion seropositive to HPV types 6, 11, 16, and 18. We compared type-specific results by age group against those from a baseline 2005 Australian HPV serosurvey. There were decreases in proportion seropositive for every HPV type across all age groups, many statistically significant. The largest decrease was observed for HPV-11, with decreases of 8- and 9-fold for ages 20-29 and 30-39 years, respectively. Despite substantial reductions in seroprevalence, at least 9% of males were seropositive for at least 1 of the 4 HPV types. This is the first serosurvey confirming broad population-level impact in males from female HPV vaccination. Our research may assist policy makers considering implementing HPV vaccination programs.

The economic burden of human papillomavirus-related precancers and cancers in Sweden.

BackgroundHigh-risk (HR) human papillomavirus (HPV) infection is an established cause of malignant disease. We used a societal perspective to estimate the cost of HR HPV-related cervical, vulvar, vaginal, anal, and penile precancer and cancer, and oropharyngeal cancer in Sweden in 2006, 1 year before HPV vaccination became available in the country.Materials and methodsThis prevalence-based cost-of-illness study used diagnosis-specific data from national registries to determine the number of HR HPV-related precancers and cancers. The HR HPV-attributable fractions of these diseases were derived from a literature review and applied to the total burden to estimate HR HPV-attributable costs. Direct costs were based on health care utilization and indirect costs on loss of productivity due to morbidity (i.e., sick leave and early retirement) and premature mortality.ResultsThe total annual cost of all HR HPV-attributable precancers and cancers was €94 million (€10.3/inhabitant). Direct costs accounted for €31.3 million (€3.4/inhabitant) of the total annual cost, and inpatient care amounted to €20.7 million of direct costs. Indirect costs made up €62.6 million (€6.9/inhabitant) of the total annual cost, and premature mortality amounted to €36 million of indirect costs. Cervical precancer and cancer was most costly (total annual cost €58.4 million). Among cancers affecting both genders, anal precancer and cancer, and oropharyngeal cancer were the most costly (€11.2 million and €11.9 million, respectively). For oropharyngeal cancer, males had the highest health care utilization and represented 71% of the total annual cost. Penile precancer and cancer was least costly (€2.6 million).ConclusionThe economic burden of HR HPV-related precancers and cancers is substantial. The disease-related management and treatment costs we report are relevant as a point of reference for future economic evaluations investigating the overall benefits of HPV vaccination in females and males in Sweden.

Development and Validation of the Human Papillomavirus Attitudes and Beliefs Scale in a National Canadian Sample

Parents' human papillomavirus (HPV) vaccination decision-making is strongly influenced by their attitudes and beliefs toward vaccination. To date, psychometrically evaluated HPV vaccination attitudes scales have been narrow in their range of measured beliefs and often limited to attitudes surrounding female HPV vaccination. The study aimed to develop a comprehensive, validated and reliable HPV vaccination attitudes and beliefs scale among parents of boys. Data were collected from Canadian parents of 9- to 16-year-old boys using an online questionnaire completed in 2 waves with a 7-month interval. Based on existing vaccination attitudes scales, a set of 61 attitude and belief items were developed. Exploratory and confirmatory factor analyses were conducted. Internal consistency was evaluated with Cronbach's α and stability over time with intraclass correlations. The HPV Attitudes and Beliefs Scale (HABS) was informed by 3117 responses at time 1 and 1427 at time 2. The HABS contains 46 items organized in 9 factors: Benefits (10 items), Threat (3 items), Influence (8 items), Harms (6 items), Risk (3 items), Affordability (3 items), Communication (5 items), Accessibility (4 items), and General Vaccination Attitudes (4 items). Model fit at time 2 were: χ/df = 3.13, standardized root mean square residual = 0.056, root mean square error approximation (confidence interval) = 0.039 (0.037-0.04), comparative fit index = 0.962 and Tucker-Lewis index = 0.957. Cronbach's αs were greater than 0.8 and intraclass correlations of factors were greater than 0.6. The HABS is the first psychometrically-tested scale of HPV attitude and beliefs among parents of boys available for use in English and French. Further testing among parents of girls and young adults and assessing predictive validity are warranted.

Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study

Australia introduced a national quadrivalent human papillomavirus (4vHPV) vaccination programme for girls and young women in April, 2007. The HPV genotypes targeted by the female vaccine could also affect the protection afforded to heterosexual men. We examined the prevalence of 4vHPV targeted vaccine genotypes and the nine-valent HPV (9vHPV)-targeted vaccines genotypes among sexually active, predominantly unvaccinated heterosexual men from 2004 to 2015. We did a retrospective, observational study of urine and urethral swab specimens from heterosexual men aged 25 years or younger attending the Melbourne Sexual Health Centre between July 1, 2004, and June 30, 2015, who tested positive for Chlamydia trachomatis. We extracted HPV DNA and used the PapType HPV assay to detect 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and two low-risk genotypes (6 and 11). We calculated the prevalence of any HPV genotype, genotypes 6 or 11, genotypes 16 or 18, genotypes in the 4vHPV group (6, 11, 16, or 18), five additional genotypes in the 9vHPV group (31, 33, 45, 52, or 58), and non-vaccine-targeted genotypes (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, or 68). We obtained data between July 1, 2004, and June 30, 2015, and did the data analysis in December, 2015. Of 1764 specimens obtained, we included 1466 in our final analysis (the others were excluded because they had indeterminate results or were duplicates). The prevalence of any HPV genotype and genotypes 31, 33, 45, 52, and 58 did not change from 2004-05 to 2014-15, but we noted reductions in genotypes 6 and 11 (from 12% [95% CI 6-21%], to 3% [1-7%], ptrend=0·008), 16 and 18 (from 13% [95% CI 7-22%] to 3% [1-6%], ptrend<0·0001), and 4vHPV-targeted genotypes (from 22% [95% CI 14-33%] to 6% [3-10%], ptrend<0·0001). Prevalence of non-vaccine-targeted genotypes increased from 16% [95% CI 9-26%] to 22% [17-29%], ptrend<0·0001). In Australian-born men, 4vHPV-targeted genotype prevalence decreased from 11 of 55 [20%, 95% CI 10-33%] to two of 74 [3%, 0-11%], ptrend<0·0001); an even greater decline occurred in Australian-born men aged 21 years or younger (from four of 13 [31%, 95% CI 9-61%] to none of 25; ptrend<0·0001). Genotypes 16 and 18 decreased (adjusted prevalence ratio [PR] 0·32, 95% CI 0·14-0·74; p=0·008) but not genotypes 6 and 11 (adjusted PR 0·50, 0·16-1·56; p=0·234) in the postvaccination period among men who had arrived in Australia within 2 years from countries with a bivalent vaccine (2vHPV) programme (England, Scotland, Wales, Cook Islands, Northern Ireland, or the Netherlands), compared with the prevaccination period. No change was noted in 4vHPV genotypes in men born overseas in other countries. The marked reduction in prevalence of 4vHPV genotypes among mainly unvaccinated Australian-born men suggests herd protection has occurred from the female vaccination programme. Additionally, the decline in genotypes 16 and 18, but not genotypes 6 and 11, among overseas-born men predominantly from countries with a 2vHPV vaccine programme suggests that these men received benefits from herd protection for genotypes 16 and 18 from their vaccinated female partners in their own countries. These reductions could translate to reductions in HPV-related malignant conditions in men, even in countries with female-only vaccination programmes. The Australian National Health and Medical Research Council Program.

Trends of incidence and survival in squamous-cell carcinoma of the anal canal in France: a population-based study.

Data on anal cancer epidemiology are rare. The aim of this study was to report on trends of incidence and survival for anal cancer in France before the implementation of the human papilloma virus vaccine. This analysis was carried out on 1150 squamous-cell carcinomas of the anal canal diagnosed from 1989 to 2004 in a population of 5.7 million people covered by eight population-based cancer registries. Time trends in incidence were modeled using an age-period-cohort model. Net survival rates were obtained using the recently validated unbiased Pohar-Perme estimator. The incidence of squamous-cell carcinoma of the anal canal increased from 0.2 to 0.5/100 000 person-years among men and from 0.7 to 1.3/100 000 person-years among women from 1982 to 2012. Among women, the increase peaked after 2005, with an annual percentage change of +3.4% between 2005 and 2012, as compared with +2.6% among men. The net survival was 56% (95% confidence interval, 49-64) at 5 years and 48% (33-70) at 10 years among men. It was higher among women, at 65% (61-69) and 56% (50-63) at 5 and 10 years, respectively. The prognosis improved between 1989-1997 and 1998-2004. This improvement was slightly greater for men than for women, thus progressively reducing the gap between sexes. The incidence of squamous-cell anal canal cancer increased slightly among both sexes, but the increase was more marked among women than among men. The potential benefit of prophylactic female human papilloma virus vaccination against cervical cancer in France should be further evaluated.

Association between sexual mixing and genital warts in heterosexual men in Australia: the herd protection from the female human papillomavirus vaccination program.

Australian-born women aged ≤32 years were eligible for the free female human papillomavirus (HPV) vaccination program introduced in 2007. A total of 1165 heterosexual couples attending the Melbourne Sexual Health Centre between 2011 and 2014 were included in this analysis. Findings showed the odds of having penile warts was 0.52-fold lower among men who had a female partner aged ≤32 years compared with men who had a female partners aged >32 years. This suggests men would have received herd protection from their female partners and hence they are at lower risk of acquiring genital warts.

Assortative sexual mixing among heterosexuals in Australia: implications for herd protection in males from a female human papillomavirus vaccination program.

The aim was to investigate the assortative sexual mixing by country of birth among heterosexuals in Australia. An analysis of 1060 heterosexual couples who attended the Melbourne Sexual Health Centre between 2011 and 2014 was conducted. Of the 1060 couples, 27% (n = 281) were both Australian-born men and women, and 42% (n = 445) were both overseas-born. Of the 171 couples with women aged ≤21 years, 41% (n = 70) were both born in Australia and 33% (n = 56) were both born overseas. A strong assortative mixing pattern by country of birth was observed among all 1060 couples (r = 0.361; 95% CI: 0.320-0.403), and among 171 couples with women aged ≤21 years (r = 0.481; 95% CI: 0.379-0.584).

Summary of the National Advisory Committee on Immunization's Update on the recommended human papillomavirus (HPV) vaccine immunization schedule.

Human papillomavirus (HPV) infections are the most common sexually transmitted infections. In the absence of vaccination, it is estimated that 75% of sexually active Canadians will have a sexually transmitted HPV infection at some point in their lives. Canada's National Advisory Committee on Immunization (NACI) has recommended a three-dose immunization schedule with HPV vaccine for females 9 years of age and older and for males between 9 and 26 years of age, since 2007 and 2012, respectively. To outline the evidence on a two-dose HPV vaccine schedule and to make recommendations for the optimal HPV immunization schedule in Canada. NACI reviewed the evidence used by the World Health Organization's (WHO's) Strategic Advisory Group of Experts (SAGE) on Immunization for the two-dose HPV immunization schedule recommended for immunocompetent girls 9 to 14 years of age and conducted an additional review of literature for studies not included in, or published after, the SAGE review. A knowledge synthesis was performed then NACI approved specific recommendations and elucidated the rationale and relevant considerations. Based on the evidence available to date, a two-dose HPV immunization schedule among immunocompetent 9- to 14-year-olds is expected to provide similar protective efficacy compared to a three-dose schedule in immunocompetent individuals aged 9 to 26 years. While all studies reviewed included only females, there is no reason to believe that the data would be different in males, given that data from three-dose trials demonstrates similar immune responses. Administration of two doses of HPV vaccine rather than three may increase acceptability by students, parents and health care professionals alike, and may lead to improved HPV immunization coverage and efficiencies by public health agencies. The duration of protection of either two doses or three doses of HPV vaccine is not yet known; research is encouraged to determine whether there is need for a booster dose. Based on the evidence available to date, a two-dose HPV immunization schedule (given at least six months apart) among immunocompetent 9- to 14-year-olds may be considered by individuals and jurisdictions to allow for potential cost savings and other individual and programmatic advantages. A three-dose schedule should be used in individuals 15 years of age and older, as well as immunocompromised individuals and immunocompetent HIV-infected individuals. The new and complete set of current recommendations for HPV vaccines will be published in the updated HPV chapter in the Canadian Immunization Guide in the near future.

Incidence of Sexually Transmitted Infections After Human Papillomavirus Vaccination Among Adolescent Females

Human papillomavirus (HPV) vaccination rates among US females remain low, in part because of concerns that HPV vaccination may promote unsafe sexual activity by lowering perceived risks of acquiring a sexually transmitted infection (STI). To study whether HPV vaccination of females is associated with increases in STI rates. Using a large, longitudinal insurance database of females aged 12 to 18 years insured from January 1, 2005, through December 31, 2010, in the United States, we examined whether HPV vaccination was associated with an increase in incident STIs among females who were vaccinated compared with those who were not. We defined STIs as one or more medical claims for any of the following infections in a given quarter: chlamydia, gonorrhea, herpes, human immunodeficiency virus or AIDS, or syphilis. We used difference-in-difference analysis to compare changes in STI rates among HPV-vaccinated females before and after vaccination (index quarter) to changes among age-matched nonvaccinated females before and after the index quarter. We analyzed whether effects varied according to age and prior contraceptive medication use. Rates of STIs. The rates of STIs in the year before vaccination were higher among HPV-vaccinated females (94 of 21 610, 4.3 per 1000) compared with age-matched nonvaccinated females (522 of 186 501, 2.8 per 1000) (adjusted odds ratio, 1.37; 95% CI, 1.09-1.71; P = .007). The rates of STIs increased for the vaccinated (147 of 21 610, 6.8 per 1000) and nonvaccinated (781 of 186 501, 4.2 per 1000) groups in the year after vaccination (adjusted odds ratio, 1.50; 95% CI, 1.25-1.79; P < .001). The difference-in-difference odds ratio was 1.05 (95% CI, 0.80-1.38; P = .74), implying that HPV vaccination was not associated with an increase in STIs relative to growth among nonvaccinated females. Similar associations held among subgroups aged 12 through 14 years and aged 15 through 18 years and among females with contraceptive use in the index quarter. Human papillomavirus vaccination was not associated with increases in STIs in a large cohort of females, suggesting that vaccination is unlikely to promote unsafe sexual activity.

Human Papillomavirus Vaccination of Females in a Large Health Claims Database in the United States, 2006–2012

PurposeInformation on vaccine utilization from a variety of sources is useful to give a status of the vaccine program and define opportunities to improve uptake. We evaluated MarketScan Commercial Claims and Encounters database on human papillomavirus (HPV) vaccine initiation and completion of all three doses among girls/women from 2006 to 2012. MethodsData were obtained from the 2006–2012 MarketScan Commercial Claims and Encounters database. The study population included female enrollees aged 11–26 years who were continuously enrolled in the same private insurance plan from 2006 to 2012 (n = 407,371). We evaluated overall and yearly vaccine initiation and completion, demographic characteristics associated with vaccine initiation, clinical visits in which vaccine was given, and missed opportunities for vaccination. ResultsBy the end of 2012, 36.9% of females aged 11–26 years had received at least one HPV vaccine dose. Vaccination coverage was highest among females aged 17–18 years (49.3%) and aged 15–16 years (43.1%) and lowest among females aged 11–12 years (16.8%). Between 2007 and 2012, 96.1% of the 246,192 unvaccinated females had at least one missed opportunity (a heath care visit without HPV vaccine administered). ConclusionsOver a 6 year period, HPV vaccine initiation was lowest in the girls aged 11–12 years. Importantly, most (96.1%) unvaccinated females had at least one missed vaccination opportunity, and providers and health systems should focus efforts on using existing visits for vaccination.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis

Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. The Canadian Institutes of Health Research.

HPV vaccination in women aged 27 to 45years: what do general practitioners think?

BackgroundAlthough the Human Papillomavirus (HPV) vaccine is registered in Australia for females aged 9 to 45 years, females aged 27 to 45 years have shown limited vaccine uptake. Our study explored general practitioners’ (GPs) views concerning HPV vaccination of females in this age group, with particular focus on the barriers and the facilitators to the delivery of the HPV vaccine.MethodsSemi-structured telephone interviews were conducted with 24 randomly selected general practitioners from metropolitan Melbourne. Questions were based on a theoretical framework that explained the barriers and facilitators to professional behaviour change.ResultsAccording to the GPs, the major barriers to the uptake of the HPV vaccine included the cost of the vaccine, time constraints, and the three-dose schedule. Other barriers that were identified included GPs’ and patients’ beliefs that females in this age group were at low risk of contracting HPV, lack of awareness about the vaccine, and uncertainty about the benefits of this vaccine for females in this age group. In contrast, the facilitators that were identified included the availability of the vaccine on site, the availability of vaccine clinics or nurses for administering the vaccine, the availability of information related to the vaccine either on site or online, and positive opinions from experts in the field.ConclusionsOur study has identified some of the barriers and facilitators to the delivery and uptake of the HPV vaccine in females aged 27 to 45 years, as perceived by GPs. Further studies should be conducted to determine which of these should be targeted or prioritised for intervention. The views of women in this age group should also be considered as these would also be influential in designing effective intervention strategies for improving the delivery and uptake of the HPV vaccine.

Cost-effectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study.

Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support. We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects. In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690,000 cases of cervical cancer and 420,000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200,000 cases of cervical cancer and 100,000 deaths in some of the highest-burden countries. Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions. WHO.