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Human papillomavirus (HPV) causes cervical as well as other cancers. Racial and ethnic disparities in cervical cancer incidence and mortality in the United States are well documented. HPV vaccination has been recommended in the United States since 2006 and is expected to prevent HPV-attributable cancers in all racial/ethnic groups. Quadrivalent HPV vaccine-type (HPV6/11/16/18) and nonvaccine-type cervicovaginal HPV prevalences were estimated from National Health and Nutrition Examination Surveys in 2015-2018 (vaccine era) and 2003-2006 (prevaccine era) data. Prevalence ratios comparing 2015-2018 to 2003-2006 were calculated among sexually experienced Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Mexican American (MA) females aged 14-24 years. Quadrivalent HPV vaccine-type prevalence declined 82% (CI: 60%-92%) among NHW, 86% (CI: 64%-95%) among NHB, and 100% among MA females, forecasting future reductions in cervical cancer across racial/ethnic groups.

Objectives: Although invasive cervical cancer (ICC) rates have declined since the advent of screening, the annual age-adjusted ICC rate in the United States remains 7.5 per 100,000 women. Failure of recommended screening and management often precedes ICC diagnoses. The study aimed to evaluate characteristics of women with incident ICC, including potential barriers to accessing preventive care. Materials and Methods: We abstracted medical records for patients with ICC identified during 2008-2020 in five U.S. population-based surveillance sites covering 1.5 million women. We identified evidence of adverse social and medical conditions, including uninsured/underinsured, language barrier, substance use disorder, incarceration, serious mental illness, severe obesity, or pregnancy at diagnosis. We calculated descriptive frequencies and compared potential barriers by race/ethnicity, and among women with and without symptoms at diagnosis using chi-square tests. Results: Among 1,606 women with ICC (median age: 49 years; non-White: 47.4%; stage I: 54.7%), the majority (68.8%) presented with symptoms. Forty-six percent of women had at least one identified potential barrier; 15% had multiple barriers. The most common potential barriers among all women were being underinsured/uninsured (17.3%), and language (17.1%). Presence of any potential barrier was more frequent among non-White women and women with than without symptoms ( p  < 0.05). Conclusions: In this population-based descriptive study of women with ICC, we identified adverse circumstances that might have prevented women from seeking screening and treatment to prevent cancer. Interventions to increase appropriate cervical cancer screening and management are critical for reducing cervical cancer rates.

Background: The epidemiology of human papillomavirus (HPV) in women has been well documented. Less is known about the epidemiology of HPV in men. We aim to provide updated global and regional pooled overall, type-specific, and age-specific prevalence estimates of genital HPV infection in men., Methods: We conducted a systematic review and meta-analysis to assess the prevalence of genital HPV infection in the general male population. We searched Embase, Ovid MEDLINE, and the Global Index Medicus for studies published between Jan 1, 1995, and June 1, 2022. Inclusion criteria were population-based surveys in men aged 15 years or older or HPV prevalence studies with a sample size of at least 50 men with no HPV-related pathology or known risk factors for HPV infection that collected samples from anogenital sites and used PCR or hybrid capture 2 techniques for HPV DNA detection. Exclusion criteria were studies conducted among populations at increased risk of HPV infection, exclusively conducted among circumcised men, and based on urine or semen samples. We screened identified reports and extracted summary-level data from those that were eligible. Data were extracted by two researchers independently and reviewed by a third, and discrepancies were resolved by consensus. We extracted only data on mucosal α-genus HPVs. Global and regional age-specific prevalences for any HPV, high-risk (HR)-HPV, and individual HPV types were estimated using random-effects models for meta-analysis and grouped by UN Sustainable Development Goals geographical classification., Findings: We identified 5685 publications from database searches, of which 65 studies (comprising 44 769 men) were included from 35 countries. The global pooled prevalence was 31% (95% CI 27-35) for any HPV and 21% (18-24) for HR-HPV. HPV-16 was the most prevalent HPV genotype (5%, 95% CI 4-7) followed by HPV-6 (4%, 3-5). HPV prevalence was high in young adults, reaching a maximum between the ages of 25 years and 29 years, and stabilised or slightly decreased thereafter. Pooled prevalence estimates were similar for the UN Sustainable Development Goal geographical regions of Europe and Northern America, Sub-Saharan Africa, Latin America and the Caribbean, and Australia and New Zealand (Oceania). The estimates for Eastern and South-Eastern Asia were half that of the other regions., Interpretation: Almost one in three men worldwide are infected with at least one genital HPV type and around one in five men are infected with one or more HR-HPV types. Our findings show that HPV prevalence is high in men over the age of 15 years and support that sexually active men, regardless of age, are an important reservoir of HPV genital infection. These estimates emphasise the importance of incorporating men in comprehensive HPV prevention strategies to reduce HPV-related morbidity and mortality in men and ultimately achieve elimination of cervical cancer and other HPV-related diseases., Funding: Instituto de Salud Carlos III, European Regional Development Fund, Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, and Horizon 2020., Translations: For the Spanish and French translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests The Cancer Epidemiology Research Program (with which LB, LA, and GA are affiliated) has received sponsorship for grants from Merck and HPV test kits at no cost from Roche for research purposes. ARG reports payments from Merck to her institution, and as consulting fees to herself, and payments from Merck for participation on an advisory board. All other authors declare no competing interests., (© 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

The annual direct medical cost attributable to human papillomavirus (HPV) in the United States over the period 2004-2007 was estimated at $9.36 billion in 2012 (updated to 2020 dollars). The purpose of this report was to update that estimate to account for the impact of HPV vaccination on HPV-attributable disease, reductions in the frequency of cervical cancer screening, and new data on the cost per case of treating HPV-attributable cancers. Based primarily on data from the literature, we estimated the annual direct medical cost burden as the sum of the costs of cervical cancer screening and follow-up and the cost of treating HPV-attributable cancers, anogenital warts, and recurrent respiratory papillomatosis (RRP). We estimated the total direct medical cost of HPV to be $9.01 billion annually over the period 2014-2018 (2020 U.S. dollars). Of this total cost, 55.0% was for routine cervical cancer screening and follow-up, 43.8% was for treatment of HPV-attributable cancer, and less than 2% was for treating anogenital warts and RRP. Although our updated estimate of the direct medical cost of HPV is slightly lower than the previous estimate, it would have been substantially lower had we not incorporated more recent, higher cancer treatment costs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Declines in cervical intraepithelial neoplasia grades 2 to 3 and adenocarcinoma in situ (CIN2+) observed among young women suggest impact from human papillomavirus (HPV) vaccination. To further evaluate vaccine impact including cross-protection and type replacement, we described high-risk (HR)-HPV type-specific cervical precancer incidence rates among women aged 20 to 39 years, 2008 to 2016. We analyzed cross-sectional population-based data on 18 344 cases of CIN2+ from a 5-site surveillance system. Diagnostic specimens were tested for individual HPV types, including 14 HR-HPV types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68). We estimated age-specific annual HR-HPV type-specific CIN2+ incidence per 100 000 screened women for individual types, vaccine HR-HPV types (HPV16/18) and nonvaccine HR-HPV types (non-HPV16/18). We evaluated trends using average annual percent changes (AAPC) and 95% confidence intervals (CI), and estimated total declines by comparing 2015-2016 to 2008-2009 using incidence rate ratios. Among 20-24-year-olds, HPV16/18-CIN2+ declined from 2008 through 2016 (AAPC: -21.3%, 95% CI: -28.1%, -13.8%), whereas no trend was observed for non-HPV16/18-CIN2+ (AAPC: -1.8%, 95% CI: -8.1%, 4.9%). After 2010, CIN2+ among 20-24-year-olds was more often caused by nonvaccine vs vaccine HR-HPV types. No significant declining trends were observed in older age groups. In 2015-2016 compared with 2008-2009, HPV16-CIN2+ declined 78%, HPV18-CIN2+ 72% and HPV31-CIN2+ 51% among 20-24-year-olds; no increases were observed in type-specific CIN2+ incidence. Among 25-29-year-olds, HPV16-CIN2+ declined 18%; CIN2+ attributed to seven nonvaccine types increased significantly. No significant declines were observed in older groups. Significant declines in HPV16/18-CIN2+ in 20-24-year-olds and HPV16-CIN2+ in 25-29-year-olds corroborate impact of HPV vaccination. A declining trend in HPV31-CIN2+ is consistent with cross-protection from vaccination., (© 2022 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies., Methods: We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding., Results: Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses., Conclusion: Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. LM, MD, MJ, JMB, GO, ARK, and MB are members of the Single-Dose HPV vaccine evaluation consortium., (Published by Elsevier Ltd.)

Background: Racial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management., Methods: Pooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided., Results: For all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70)., Conclusion: The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types., (Published by Oxford University Press 2022. This work is written by US Government employees and is in the public domain in the US.)

Objectives: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007., Materials and Methods: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017., Results: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups., Conclusions: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement., Competing Interests: A.L.N. has received research funding from Pfizer, Takeda, MedImmune, and Merck for unrelated studies. N.P.K. has received research funding from Merck, GlaxoSmithKline, Sanofi Pasteur, Novartis, MedImmune, Pfizer, and Protein Sciences (now Sanofi Pasteur) for unrelated studies. S.W. has received research funding from GlaxoSmithKline for an unrelated study. The other authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Background: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+)., Methods: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination., Results: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI, 60%-71%) for UTD, 33% (95% CI, 18%-46%) for 2 doses-not UTD, and 40% (95% CI, 27%-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI, 64%-79%) for UTD, 39% (95% CI, 10%-58%) for 2 doses-not UTD, and 48% (95% CI, 25%-63%) for 1 dose. VE was higher for vaccination at age <20 than ≥20 years., Conclusions: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination., Impact: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness., (©2021 American Association for Cancer Research.)

Objective: The aim of the study was to describe trends in human papillomavirus (HPV) testing preceding diagnosis of cervical precancer during a time of changing screening recommendations., Materials and Methods: We conducted a cross-sectional analysis of data from active, population-based, laboratory surveillance among 1.5 million residents of 5 areas in the United States. We included women aged 21-39 years diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ (collectively, CIN2+) during 2008-2016, who had a cytology and/or HPV test before diagnosis (n = 16,359)., Results: The proportion of women with an HPV test preceding CIN2+ increased from 42.9% in 2008 to 73.3% in 2016 (p < .01); testing increased in all age groups (21-24 y: 35.3% to 47.6%, 25-29 y: 40.9% to 64.1%, 30-39 y: 51.7% to 85.9%, all p < .01). The HPV testing varied by cytology result and was highest among women with atypical squamous cells of unknown significance (n = 4,310/4,629, 93.1%), negative for intraepithelial lesion or malignancy (n = 446/517, 86.3%), and atypical glandular cells (n = 145/257, 56.4%). By 2016, at least half of all cases in every surveillance area had an HPV test before diagnosis., Conclusions: During 2008-2016, the proportion of women with an HPV test preceding CIN2+ increased significantly for all age groups, cytology results, and surveillance areas. By 2016, most (85.9%) women aged 30-39 years had an HPV test, consistent with recommendations. Increasing utilization of HPV tests, which have demonstrated improved sensitivity for detecting cervical disease, may in part explain increasing rates of cervical precancer among women 30 years and older., Competing Interests: L.M.N. serves as a scientific advisor for Merck, outside of submitted work. The other authors have declared they have no conflicts of interest., (Copyright © 2021, ASCCP.)

Introduction: Human papillomavirus (HPV) can cause anogenital warts and several types of cancer, including cervical cancers and precancers. We estimated the prevalence, incidence, and number of persons with prevalent and incident HPV infections in the United States in 2018., Methods: Prevalence and incidence were estimated for infections with any HPV (any of 37 types detected using Linear Array) and disease-associated HPV, 2 types that cause anogenital warts plus 14 types detected by tests used for cervical cancer screening (HPV 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the 2013-2016 National Health and Nutrition Examination Survey to estimate prevalence among 15- to 59-year-olds, overall and by sex. Incidences in 2018 were estimated per 10,000 persons using an individual-based transmission-dynamic type-specific model calibrated to US data. We estimated number of infected persons by applying prevalences and incidences to 2018 US population estimates., Results: Prevalence of infection with any HPV was 40.0% overall, 41.8% in men, and 38.4% in women; prevalence of infection with disease-associated HPV was 24.2% in men and 19.9% in women. An estimated 23.4 and 19.2 million men and women had a disease-associated HPV type infection in 2018. Incidences of any and disease-associated HPV infection were 1222 and 672 per 10,000 persons; incidence of disease-associated HPV infection was 708 per 10,000 men and 636 per 10,000 women. An estimated 6.9 and 6.1 million men and women had an incident infection with a disease-associated HPV type in 2018., Conclusions: We document a high HPV burden of infection in the United States in 2018, with 42 million persons infected with disease-associated HPV and 13 million persons acquiring a new infection. Although most infections clear, some disease-associated HPV type infections progress to disease. The HPV burden highlights the need for continued monitoring of HPV-associated cancers, cervical cancer screening, and HPV vaccination to track and prevent disease., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Introduction: We estimated the lifetime medical costs of diagnosed cases of diseases attributable to human papillomavirus (HPV) infections acquired in 2018., Methods: We adapted an existing mathematical model of HPV transmission and associated diseases to estimate the lifetime number of diagnosed cases of disease (genital warts; cervical intraepithelial neoplasia; and cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers) attributable to HPV infections that were acquired in 2018. For each of these outcomes, we multiplied the estimated number of cases by the estimated lifetime medical cost per case obtained from previous studies. We estimated the costs of recurrent respiratory papillomatosis in a separate calculation. Future costs were discounted at 3% annually., Results: The estimated discounted lifetime medical cost of diseases attributable to HPV infections acquired in 2018 among people aged 15 to 59 years was $774 million (in 2019 US dollars), of which approximately half was accounted for by infections in those aged 15 to 24 years. Human papillomavirus infections in women accounted for approximately 90% of the lifetime number of diagnosed cases of disease and 70% of the lifetime cost attributable to HPV infections acquired in 2018 among those aged 15 to 59 years., Conclusions: We estimated the lifetime medical costs of diseases attributable to HPV infections acquired in 2018 to be $774 million. This estimate is lower than previous estimates, likely due to the impact of HPV vaccination. The lifetime cost of disease attributable to incident HPV infections is expected to decrease further over time as HPV vaccination coverage increases., Competing Interests: Conflict of Interest and Sources of Funding: Work by M.B., J.-F.L., and D.M. was supported by a contract from the Centers for Disease Control and Prevention (contract 00HCVGEB-2019-35238), a Fonds de recherche du Québec–Santé Research Scholars award (to M.B.), and a foundation scheme grant from the Canadian Institutes of Health Research (grant number FDN-143283)., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: The objective of this study was to assess incremental costs and benefits of a human papillomavirus (HPV) vaccination program expanded to include "mid-adults" (adults aged 27 through 45 years) in the United States., Methods: We adapted a previously published, dynamic mathematical model of HPV transmission and HPV-associated disease to estimate the incremental costs and benefits of a 9-valent HPV vaccine (9vHPV) program for people aged 12 through 45 years compared to a 9vHPV program for females aged 12 through 26 years and males aged 12 through 21 years., Results: A 9vHPV program for females aged 12 through 26 years and males aged 12 through 21 years was estimated to cost < $10,000 quality-adjusted life year (QALY) gained, compared to no vaccination. Expanding the 9vHPV program to include mid-adults was estimated to cost $587,600 per additional QALY gained when including adults through age 30 years, and $653,300 per additional QALY gained when including adults through age 45 years. Results were most sensitive to assumptions about HPV incidence among mid-adults, current and historical vaccination coverage, vaccine price, and the impact of HPV diseases on quality of life., Conclusions: Mid-adult vaccination is much less cost-effective than the comparison strategy of routine vaccination for all adolescents at ages 11 to 12 years and catch-up vaccination for women through age 26 years and men through age 21 years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Published by Elsevier Ltd.)

Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008-2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received ≥24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18-positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Human papillomavirus (HPV) vaccine has been recommended in the United States since 2006 for routine vaccination of girls at age 11-12 years and through age 26 years for women not previously vaccinated. Changes in vaccine-type HPV (VT) prevalence can be used to evaluate vaccine impact, including herd effects., Methods: We determined type-specific HPV in cytology specimens from women aged 20-29 years screened for cervical cancer at Kaiser Permanente Northwest in 2007 and in two vaccine era periods: 2012-2013 and 2015-2016. Detection and typing used L1 consensus PCR with hybridization for 37 types, including quadrivalent vaccine types (HPV 6/11/16/18)., Results: Among 20-24 year-olds in 2012-2013 and 2015-2016, 44% and 64% had a history of ≥1-dose vaccination. VT prevalence decreased from 13.1% in 2007 to 2.9% in 2015-2016 (prevalence ratio [PR] = 0.22; 95% confidence interval [CI] 0.17-0.29). HPV 31 prevalence was also lower in the vaccine periods compared with 2007. VT prevalence in 2015-2016 among 20-24 year-olds was lower in both vaccinated, 1.3% (PR = 0.10; 95% CI 0.06-0.16), and unvaccinated women, 5.8% (PR = 0.45; 95% CI 0.33-0.61). Among 25-29 year-olds, 21% and 32% had a history of ≥1-dose vaccination. VT prevalence decreased from 8.1% in 2007 to 5.0% in 2015-2016 (PR = 0.62; 95% CI 0.50-0.78). Non-VT high risk prevalence was higher in the vaccine periods compared with the pre-vaccine era in both age groups, however, not in 2015-2016 compared with 2012-2013., Conclusion: Within 9-10 years of vaccine introduction, VT prevalence decreased 78% among 20-24 year-olds and 38% in 25-29 year-olds. There were declines in both vaccinated and unvaccinated women, showing evidence of direct and herd protection., (Published by Elsevier Ltd.)

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., Competing Interests: All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. Linda Niccolai reports personal fees from Merck as a scientific advisor during the course of the study. No other potential conflicts of interest were disclosed.

Background: We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations., Methods: We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008-2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time., Results: A total of 16572 CIN2+ cases were reported. Among women aged 18-20 and 21-24 years, CIN2+ rates declined in all sites, whereas in women aged 25-29, 30-34, and 35-39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008-2009, rates among screened women were significantly lower for all 3 periods in women aged 18-20 years (2010-2011: IRR 0.82, 95% confidence interval [CI] 0.67-0.99; 2012-2013: IRR 0.63, 95% CI 0.47-0.85; 2014-2015: IRR 0.44, 95% CI 0.28-0.68) and lower for the latter 2 time periods in women aged 21-24 years (2012-2013: IRR 0.86, 95% CI 0.79-0.94; 2014-2015: IRR 0.61, 95% CI 0.55-0.67)., Conclusions: From 2008-2015, both CIN2+ rates and cervical cancer screening declined in women aged 18-24 years. The significant decreases in CIN2+ rates among screened women aged 18-24 years are consistent with a population-level impact of HPV vaccination., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.)

Background: The impact of human papillomavirus (HPV) vaccination has been observed in the United States through declining cervical precancer incidence in young women. To further evaluate vaccine impact, we described trends in HPV vaccine types 16/18 in cervical precancers, 2008-2014., Methods: We analyzed data from a 5-site, population-based surveillance system. Archived specimens from women age 18-39 years diagnosed with cervical intraepithelial neoplasia grades 2-3 or adenocarcinoma in situ (CIN2+) were tested for 37 HPV types. We described the proportion and estimated number of cases of CIN2+ by HPV-type groups over time. Trends in HPV16/18-positive CIN2+ were examined, overall and by vaccination status, age, histologic grade, and race/ethnicity, using Cochrane-Armitage tests., Results: In 10,206 cases, the proportion and estimated number of cases of HPV16/18-positive CIN2+ declined from 52.7% (1,235 cases) in 2008 to 44.1% (819 cases) in 2014 ( P < 0.001). Declining trends in the proportion of HPV16/18-positive CIN2+ were observed among vaccinated (55.2%-33.3%, P < 0.001) and unvaccinated (51.0%-47.3%, P = 0.03) women; ages 18-20 (48.7%-18.8%, P = 0.02), 21-24 (53.8%-44.0%, P < 0.001), 25-29 (56.9%-42.4%, P < 0.001), and 30-34 (49.8%-45.8%, P = 0.04) years; CIN2 (40.8%-29.9%, P < 0.001) and CIN2/3 (61.8%-46.2%, P < 0.001); non-Hispanic white (59.5%-47.9%, P < 0.001) and non-Hispanic black (40.7%-26.5%, P < 0.001)., Conclusions: From 2008-2014, the proportion of HPV16/18-positive CIN2+ declined, with the greatest declines in vaccinated women; declines in unvaccinated women suggest herd protection., Impact: The declining proportion of HPV16/18-positive CIN2+ provides additional evidence of vaccine impact in the United States., (©2019 American Association for Cancer Research.)

Background: Human papillomavirus (HPV) vaccines were first licensed as a three-dose series; a two-dose series is now recommended in some age groups and there is interest in possible one-dose vaccination., Methods: We conducted a systematic literature review of HPV vaccine effectiveness by number of doses, including assessment of biases and impact of varying buffer periods (time between vaccination and outcome counting)., Results: Of 3787 articles identified, 26 full articles were assessed and 14 included in our review. All studies were conducted within the context of recommended three-dose schedules of bivalent (3) or quadrivalent HPV vaccine (11). Two evaluated effectiveness for prevention of HPV prevalence, six anogenital warts, and six abnormal cervical cytology or histology. Many studies found differences between three-, two- and one-dose vaccine recipients, indicating possible differences in HPV exposure prior to vaccination or in risk behavior. Adjusted or stratified analyses were conducted to control for potential confounding. All studies found significant vaccine effectiveness with three doses, 11 with two doses at various intervals, and six with one dose. Most studies showed a relationship (not always statistically significant) between effectiveness and number of doses, with greater decreases in HPV-related outcomes with three, followed by two and one dose(s). Few studies conducted formal comparisons of three vs fewer doses. Three of four studies that examined buffer periods found higher effectiveness and a smaller difference by number of doses with longer periods., Conclusion: Most post-licensure studies report highest effectiveness with three doses; some found no statistically significant difference between two and three doses. Additionally, almost half found some effectiveness with one dose. Several biases impact estimates, with most biasing two- and one-dose results away from showing effectiveness. Future effectiveness studies, examining persons vaccinated prior to sexual activity and using methods to reduce potential sources of bias, can help inform vaccination policy., (Published by Elsevier Ltd.)

Introduction: The 2006 introduction of human papillomavirus vaccine targeted against genotypes 6, 11, 16, and 18 should result in decreased cervical dysplasia in vaccinated women. However, new cervical cancer guidelines to increase screening intervals complicate interpretation of trends. The hypothesis is that cervical dysplasia would decrease only in young vaccine-eligible women, and not older women., Methods: The authors identified Davidson County, Tennessee, women aged 18-39 years with cervical intraepithelial neoplasia (CIN) grade 2 or greater and adenocarcinoma in situ, denoted as CIN2+, through pathology reports from laboratories serving this population. Biopsy specimens for human papillomavirus genotyping were collected. Trends in CIN2+ rates and associated human papillomavirus genotypes, 2008 through 2013, were examined., Results: The authors identified 2,031 women with CIN2+. Rates of CIN2+ fell from 188.9 to 58.7 per 100,000 women aged 18-20 years (annual percentage change= -24.2, 95% CI= -41.4, -2.1) and from 495.6 to 332.4 per 100,000 women aged 21-24 years (annual percentage change= -10.2%, 95% CI= -16.3, -3.4). There was no significant change in CIN2+ rates for women aged 25-29 or 30-39 years. In biopsy specimens from 1,319 of 2,031 (65%) women, at least one human papillomavirus genotype was identified in 1,270 (96%). The prevalence of at least one of four vaccine human papillomavirus genotypes (6, 11, 16, and 18) declined from 59% in 2008 to 52% in 2013 (p=0.003)., Conclusions: Diagnosis of CIN2+ decreased in women aged 18-24 years, but not in older women. Both changes in screening and human papillomavirus vaccination could have contributed to the decline of CIN2+ in young women., (Copyright © 2018 American Journal of Preventive Medicine. All rights reserved.)

Since human papillomavirus (HPV) vaccine was first introduced for females in the United States in 2006, vaccination policy has evolved as additional HPV vaccines were licensed and new data became available. The United States adopted a gender neutral routine HPV immunization policy in 2011, the first country to do so. Vaccination coverage is increasing, although it remains lower than for other vaccines recommended for adolescents. There are various reasons for low coverage, and efforts are ongoing to increase vaccine uptake. The safety profile of HPV vaccine has been well established from 10 years of postlicensure monitoring. Despite low coverage, the early effects of the HPV vaccination program have exceeded expectations., (Published by Elsevier Inc.)

Cervical cancer incidence and mortality rates are high, particularly in developing countries. Most cervical cancers can be prevented by human papillomavirus (HPV) vaccination, screening, and timely treatment. The US Centers for Disease Control and Prevention (CDC) provides global technical assistance for implementation and evaluation of HPV vaccination pilot projects and programs and laboratory-related HPV activities to assess HPV vaccines. CDC collaborates with global partners to develop global cervical cancer screening recommendations and manuals, implement screening, create standardized evaluation tools, and provide expertise to monitor outcomes. CDC also trains epidemiologists in cancer prevention through its Field Epidemiology Training Program and is working to improve cancer surveillance by supporting efforts of the World Health Organization in developing cancer registry hubs and assisting countries in estimating costs for developing population-based cancer registries. These activities contribute to the Global Health Security Agenda action packages to improve immunization, surveillance, and the public health workforce globally.

Background: Human papillomavirus (HPV) infections cause approximately 30,700 cancers annually among US men and women, cervical cancer being the most common. Human papillomavirus vaccination is recommended routinely for US girls and boys at age 11 to 12 years, and for those not previously vaccinated, through age 26 and 21 years for women and men, respectively. Our objective was to assess current cervical cancer screening and HPV vaccination practices among sexually transmitted disease (STD) clinics in the United States., Methods: We surveyed a geographically diverse convenience sample of US STD clinics identified by members of the National Coalition of STD Directors within 65 state, territorial, and local jurisdictions. An online multiple-choice survey about clinical services was administered to clinic directors or designees during October 2014 to February 2015., Results: Survey respondents included 78 clinics from 46 states and territories. Of these clinics, 31 (39.7%) offered both cervical cancer screening and HPV vaccination, 6 (7.7%) offered cervical cancer screening only, 21 (26.9%) offered HPV vaccination only, and 20 (25.6%) offered neither cervical cancer prevention service. Among those not offering the service, the most commonly reported barrier to cervical cancer screening was time constraints (25/41, 61.0%); for HPV vaccination it was reimbursement (11/26, 42.3%)., Conclusions: By early 2015, in a geographically diverse group of 78 STD clinics, 39.7% provided nationally recommended HPV vaccination and cervical cancer screening, whereas 25.6% provided neither. Further research could identify strategies for STD clinics to reduce HPV-associated cancers by increasing provision of HPV vaccination and cervical cancer screening services, particularly among medically underserved populations.

Background: Randomized clinical trials have shown the 9-valent human papillomavirus (HPV) vaccine to be highly effective against types 31/33/45/52/58 compared with the 4-valent. Evidence on the added health and economic benefit of the 9-valent is required for policy decisions. We compare population-level effectiveness and cost-effectiveness of 9- and 4-valent HPV vaccination in the United States., Methods: We used a multitype individual-based transmission-dynamic model of HPV infection and disease (anogenital warts and cervical, anogenital, and oropharyngeal cancers), 3% discount rate, and societal perspective. The model was calibrated to sexual behavior and epidemiologic data from the United States. In our base-case, we assumed 95% vaccine-type efficacy, lifelong protection, and a cost/dose of $145 and $158 for the 4- and 9-valent vaccine, respectively. Predictions are presented using the mean (80% uncertainty interval [UI] = 10(th)-90(th) percentiles) of simulations., Results: Under base-case assumptions, the 4-valent gender-neutral vaccination program is estimated to cost $5500 (80% UI = 2400-9400) and $7300 (80% UI = 4300-11 000)/quality-adjusted life-year (QALY) gained with and without cross-protection, respectively. Switching to a 9-valent gender-neutral program is estimated to be cost-saving irrespective of cross-protection assumptions. Finally, the incremental cost/QALY gained of switching to a 9-valent gender-neutral program (vs 9-valent girls/4-valent boys) is estimated to be $140 200 (80% UI = 4200->1 million) and $31 100 (80% UI = 2100->1 million) with and without cross-protection, respectively. Results are robust to assumptions about HPV natural history, screening methods, duration of protection, and healthcare costs., Conclusions: Switching to a 9-valent gender-neutral HPV vaccination program is likely to be cost-saving if the additional cost/dose of the 9-valent is less than $13. Giving females the 9-valent vaccine provides the majority of benefits of a gender-neutral strategy., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Cervical intraepithelial neoplasia grade 2, 3, and adenocarcinoma in situ (CIN2+) lesions can be monitored as early indicators of human papillomavirus (HPV) vaccine impact. Changes to screening utilization will affect observed reductions in CIN2+ rates and complicate the interpretation of vaccine impact., Methods: From 2008 to 2012, 9119 cases of CIN2+ among 18- to 39-year-old residents of catchment areas in California, Connecticut, New York, and Oregon were reported to the HPV-IMPACT Project, a sentinel system for monitoring the population impact of HPV vaccine. Age-stratified CIN2+ incidence rates were calculated for each catchment. Annual cervical screening was estimated for California, New York, and Oregon catchments with administrative and survey data. The Cochran-Armitage test was used to examine trends., Results: From 2008 to 2012, the incidence of CIN2+ significantly decreased among 18- to 20-year-olds (California, from 94 to 5 per 100,000 women; Connecticut, from 450 to 57 per 100,000 women; New York, from 299 to 43 per 100,000 women; and Oregon, from 202 to 37 per 100,000 women; Ptrend  < .0001) and among 21- to 29-year-olds in Connecticut (from 762 to 589 per 100,000 women) and New York (from 770 to 465 per 100,000 women; Ptrend  < .001); rates did not differ among 30- to 39-year-olds. During the same period, screening rates also declined, with the largest decreases among 18- to 20-year-olds (from 67% in Oregon to 88% in California) and with smaller declines among 21- to 29-year-olds (13%-27%) and 30- to 39-year-olds (3%-21%)., Conclusions: The declines in CIN2+ detection in young women were likely due to reduced screening but could also reflect the impact of vaccination. These data illustrate challenges in interpreting CIN2+ ecologic trends in the new era of cervical cancer prevention and emphasize the importance of information such as HPV types detected in lesions to assess the impact of HPV vaccine on cervical precancers., (© 2015 American Cancer Society.)

Oncogenic human papillomavirus (HPV) infection is the cause of nearly all cervical cancers and a proportion of other anogenital and oropharyngeal cancers. A bivalent vaccine containing HPV 16 and 18 and a quadrivalent vaccine containing HPV 6, 11, 16, and 18 antigens are in use in vaccination programmes around the world. In clinical trials, three vaccine doses provided 90-100% protection against cervical infection and pre-cancer related to HPV 16 and 18 in women aged 15-26 years who were not infected at vaccination. Partial cross-protection against other HPV types has been reported but its duration is unknown. The vaccines were also efficacious at the prevention of HPV 16 and 18 infections at other anatomical sites in both sexes. Immunobridging studies allowed licensing of the vaccines for use starting at age 9 years for both sexes. Two-dose schedules elicit high antibody concentrations, leading to the recommendation of two-dose schedules for girls aged 9-14 years. Pre-licensure and post-licensure studies have provided data supporting vaccine safety. In 2014, a nonavalent vaccine containing HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens was licensed by the US Food and Drug Administration. HPV vaccination was first introduced in high-income countries owing to vaccine cost, logistic challenges, and competing health priorities. Since 2011, vaccine prices have lowered, allowing the introduction of the vaccine in some middle-income countries. Funding of the vaccine by the GAVI Alliance in 2012 led to demonstration projects in some low-income countries. By 2014, more than 57 countries had included the HPV vaccine in their national health programmes. Data from several countries have shown the effect of vaccination on HPV infection and associated disease, and provided evidence of herd immunity. Expansion of programmes to countries with the highest burden of disease is beginning, but further efforts are needed to realise the potential of HPV vaccines., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden., Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected., Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%-45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001)., Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities., Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities., (©2014 American Association for Cancer Research.)

Using a previously published dynamic model, we illustrate the potential benefits of human papillomavirus vaccination among girls currently 12 years or younger in the United States. Increasing vaccine coverage of young girls to 80% would avert 53,300 lifetime cervical cancer cases versus 30% coverage and 28,800 cases versus 50% coverage.

Background: There are limited data on the proportion who have been exposed to vaccine-type human papillomavirus (HPV) among women attending sexually transmitted disease (STD) clinics; this information could inform the potential benefits of HPV vaccination for women attending this venue., Methods: Human papillomavirus surveillance was conducted in STD clinics in Baltimore, MD; Boston, MA; Denver, CO; Los Angeles, CA; and Seattle, WA, among women receiving cervical cancer screening from January 2003 to December 2005. The women had specimens collected for cervical cytology HPV testing by L1 consensus polymerase chain reaction testing and serologic assessment for HPV 6, 11, 16, and 18 using the competitive Luminex immunoassay. Results from 880 women with adequate specimens were included. Women were HPV naïve if they were both HPV DNA negative and seronegative for a specific HPV type., Results: One hundred seventy women (19.3%) had HPV 16, 18, 6, or 11 DNA, and 418 (47.5%) were HPV 16, 18, 6, or 11 seropositive. Four hundred ten (46.6%) women were naïve to all 4 types, 570 (64.8%) were naïve to both HPV 16 and 18, and 545 (61.9%) were naïve to both HPV 6 and 11. Almost all (99.3%) women were naïve to at least 1 vaccine HPV type., Conclusions: Almost half of young women age eligible for HPV vaccine and attending STD clinics were naïve to all 4 HPV types, and more than half were naïve to both HPV 16 and 18. This assessment suggests that most young women attending this venue might benefit from HPV vaccination.

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Human papillomavirus (HPV) vaccines are available in the United States and around the world to prevent HPV-associated diseases including cervical cancer and genital warts. HPV vaccination is currently recommended for adolescents: target ages for routine and catch-up vaccinations vary by country. Because the time from vaccination to cancer development can be several decades, many studies are evaluating more immediate outcomes. In the 4 years since the vaccine was introduced, reductions in HPV vaccine type prevalence and genital warts have been reported in young females in the United States and other countries. Many questions remain about the long-term impact, but the initial studies show promising results for the relatively new HPV vaccine., (Published by Elsevier Inc.)

Purpose: Despite official recommendation for routine HPV vaccination of boys and girls at age 11-12 years, parents and providers are more likely to vaccinate their children/patients at older ages. Preferences for vaccinating older adolescents may be related to beliefs about an adolescent's sexual experience or perceived parental resistance to vaccinating children who are assumed to be sexually inexperienced., Methods: Using data from the 1995 wave of the National Longitudinal Study of Adolescent Health (ADD Health), a subset of a nationally representative sample of adolescents in grades 7 through 12 and their parents (n = 13,461), we investigated maternal underestimation of adolescent sexual experience., Results: About one third (34.8%) of adolescents reported being sexually experienced and of these, 46.8% of their mothers inaccurately reported that their child was not sexually experienced. Underestimation varied by adolescent age with 78.1% of mothers of sexually active 11-13-year-olds reporting their child was not sexually active, compared with 56.4% of mothers of sexually active 14-16-year-olds and only 34.4% of mothers of 17-18-year-olds., Conclusions: Although most adolescents are not sexually active at age 11 or 12 years, waiting until a parent thinks a child is sexually active could result in missed opportunities for prevention., (Published by Elsevier Inc.)

Background: The objective of this study was to estimate the number of years after onset of a quadrivalent HPV vaccination program before notable reductions in genital warts and cervical intraepithelial neoplasia (CIN) will occur in teenagers and young adults in the United States., Methods: We applied a previously published model of HPV vaccination in the United States and focused on the timing of reductions in genital warts among both sexes and reductions in CIN 2/3 among females. Using different coverage scenarios, the lowest being consistent with current 3-dose coverage in the United States, we estimated the number of years before reductions of 10%, 25%, and 50% would be observed after onset of an HPV vaccination program for ages 12-26 years., Results: The model suggested female-only HPV vaccination in the intermediate coverage scenario will result in a 10% reduction in genital warts within 2-4 years for females aged 15-19 years and a 10% reduction in CIN 2/3 among females aged 20-29 years within 7-11 years. Coverage had a major impact on when reductions would be observed. For example, in the higher coverage scenario a 25% reduction in CIN2/3 would be observed with 8 years compared with 15 years in the lower coverage scenario., Conclusions: Our model provides estimates of the potential timing and magnitude of the impact of HPV vaccination on genital warts and CIN 2/3 at the population level in the United States. Notable, population-level impacts of HPV vaccination on genital warts and CIN 2/3 can occur within a few years after onset of vaccination, particularly among younger age groups. Our results are generally consistent with early reports of declines in genital warts among youth., (Published by Elsevier Ltd.)

Background: Current vaccines protect against 2 human papillomavirus (HPV) types, HPV 16 and 18, which are associated with 70% of cervical cancers and 50% of high-grade cervical lesions. HPV type distribution was examined among women with high-grade lesions by individual and area-based measures of race, ethnicity, and poverty., Methods: This analysis included 832 women aged 18 to 39 years reported to a surveillance registry in Connecticut during 2008 to 2010. Diagnostic specimens were obtained for HPV DNA testing. Individual measures were obtained from surveillance reports, medical records, and patient interviews. Cases were geocoded to census tracts and linked to area-based measures of race, ethnicity, and poverty. Statistical analysis included use of generalized estimating equations., Results: Overall, 44.8% of women had HPV 16/18. In a multivariate model controlled for confounding by age and diagnosis grade, black race (adjusted prevalence ratio [aPR] = 0.54, 95% confidence interval [CI] = 0.34-0.88), Hispanic ethnicity (aPR = 0.59, 95% CI = 0.40-0.88), and higher area-based poverty (aPR = 0.59, 95% CI = 0.40-0.87) were associated with a lower likelihood of HPV 16/18 positivity. Black and Hispanic women were less likely to have HPV 16/18 than white women across all levels of area-based measures., Conclusions: Black race, Hispanic ethnicity, and higher area-based poverty are salient predictors of lower HPV 16/18 positivity among women with high-grade cervical lesions. These data suggest that HPV vaccines might have lower impact among black and Hispanic women and those living in high poverty areas. These findings have implications for vaccine impact monitoring, vaccination programs, and new vaccine development., (Copyright © 2013 American Cancer Society.)

Background: Human papillomavirus (HPV) vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN) women., Methods: Cases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections) and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics) with additional INNO-LiPA HPV Genotyping Assay (Innogenetics) testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types., Results: Of 62 cervical cancer specimens evaluated, 57 (91.9%) contained one or more HPV types. Thirty-eight (61.2%) cancers contained HPV types 16 or 18, and 18 (29%) contained an oncogenic type other than type 16 or 18., Conclusions: Overall, almost two-thirds (61.2%) of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women.

Purpose: Two human papillomavirus (HPV) vaccines are available to prevent cervical cancer. One early measure of HPV vaccine impact would be a reduction in vaccine-related HPV types (HPV 6, 11, 16, or 18, or HPV 16, 18) in cervical samples from young women. We aimed to assess feasibility of specimen collection and baseline HPV prevalence in an integrated healthcare delivery system., Methods: Residual cervical specimens collected during routine cervical cancer screening (2006-2008) were retained consecutively from eligible females aged 11-29 years, stratified by age group. Specimens were evaluated for 37 HPV genotypes using the Roche Linear Array assay., Results: Of 10,124 specimens submitted, 10,103 (99 %) were adequate for HPV testing. Prevalence of HPV 6, 11, 16, or 18 genotype was 11.4 % overall and was the highest in the youngest age group (18.1 % in the 11-19-year-olds, 12.5 % in the 20-24-year-olds, and 7.0 % in the 25-29-year-olds)., Conclusions: HPV types 6, 11, 16, or 18 prevalence could be measured over time to assess early HPV vaccine impact using residual specimens from an integrated healthcare delivery system, particularly if sampling focused on young women.

Background: Two vaccines protect against human papillomaviruses (HPV) 16 and 18, which cause 70% of cervical cancer and 50% of cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+). Monitoring HPV types in CIN2+ may be used to assess HPV vaccine impact., Methods: As part of a multisite vaccine impact monitoring project (HPV-IMPACT), biopsy specimens used to diagnose CIN2+ were obtained for HPV DNA typing for women aged 18-39 years., Results: Among 4,121 CIN2+ cases reported during 2008-2009 in 18- to 39-year-old women 3058 (74.2%) were tested; 96% were HPV DNA positive. HPV 16 was most common (49.1%), followed by HPV 31 (10.4%) and HPV 52 (9.7%). HPV 18 prevalence was 5.5% overall. Proportion of CIN2+ cases associated with HPV 16/18 was highest (56.3%) in 25- to 29-year-old women. HPV 16/18-associated lesions were less common in non-Hispanic blacks (41.9%) and Hispanics (46.3%) compared with non-Hispanic whites (59.1%) (P < .0001); the difference remained significant when adjusted for covariates. Compared to non-Hispanic whites, HPV 35 and 58 were significantly more common in non-Hispanic blacks (14.5% vs 4.2%; 12.3% vs 3.4%) and HPV 45 was higher in Hispanics (3.7% vs 1.5%)., Conclusions: Age and racial/ethnic differences in HPV type distribution may have implications for vaccine impact and should be considered in monitoring trends.

Objective: To estimate racial, ethnic, and socioeconomic differences in human papillomavirus (HPV) vaccination history among women aged 18-27 years with precancerous cervical lesions diagnosed, barriers to vaccination, and timing of vaccination in relation to the abnormal cytology result that preceded the diagnosis of the cervical lesion., Methods: High-grade cervical lesions are reportable conditions in Connecticut for public health surveillance. Telephone interviews and medical record reviews were conducted during 2008-2010 for women (n=269) identified through the surveillance registry., Results: Overall, 43% of women reported history of one or more doses of HPV vaccine. The mean age at vaccination was 22 years. Publicly insured (77%) and uninsured (85%) women were more likely than privately insured women (48%) to report no history of vaccination (P<.05). Among unvaccinated women, being unaware of HPV vaccine was reported significantly more often among Hispanics than non-Hispanics (31% compared with 13%, P=.02) and among those with public or no insurance compared with those with private insurance (26% and 36% compared with 6%, P<.05 for both). The most commonly reported barrier was lack of provider recommendation (25%). Not having talked to a provider about vaccine was reported significantly more often among those with public compared with private insurance (41% compared with 18%, P<.001). Approximately 35% of women received vaccine after an abnormal cytology result; this occurred more frequently among African American women compared with white women (80% compared with 30%, P<.01)., Conclusion: Catch-up vaccination strategies should focus on provider efforts to increase timely coverage among low-income and minority women.

The following paper describes a collaboration between the Centers for Disease Control and Prevention and five Emerging Infections Program sites to develop a comprehensive population-based approach to monitoring human papillomavirus (HPV) vaccine impact on cervical cancer precursors and associated HPV genotypes. The process of establishing this novel monitoring system is described, and development details such as enumeration of sources for reporting cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ, approaches to case ascertainment, electronic reporting, and HPV typing are outlined. Implementation of a feasible and sustainable surveillance system for HPV-associated cervical precancers will enable evaluation of the direct impact of HPV vaccination.

Background: HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens., Methods: Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays., Findings: LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions., Conclusions: We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.

Purpose: To assess availability of human papillomavirus (HPV) vaccine at medical practices in an area with elevated cervical cancer rates., Methods: During July-November 2007, we conducted a telephone survey of staff at medical practices providing outpatient care to 9- to 26-year-old females in four North Carolina counties with elevated cervical cancer rates. We assessed availability of HPV vaccine and concerns about its provision., Results: Staff from 71 of 96 eligible practices completed a full interview. Overall, 62% of these practices had HPV vaccine available to patients (family practice, 74%; pediatrics, 75%; obstetrics-gynecology, 64%; internal medicine, 15%). In multivariate analysis, practice characteristics that independently predicted a lower likelihood of carrying HPV vaccine were having at least 50% African-American patient population (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.06-0.63) and providing only privately purchased (and no state-supplied) vaccines (OR 0.19, 95% CI 0.06-0.63). HPV vaccine nonproviders were significantly more likely than HPV vaccine providers to report "large" concerns about the up-front costs of purchasing HPV vaccine (52% vs. 27%, p < .05) and late reimbursement (33% vs. 14%, p < .05)., Conclusions: Approximately 1 year after its introduction, HPV vaccine was available at three-quarters of family practice and pediatrics practices, two-thirds of obstetrics-gynecology practices, and few internal medicine practices in an area with elevated cervical cancer rates. Practices' concerns about cost and reimbursement have implications for accessibility of HPV vaccine to those who need it most.

Purpose: We assessed human papillomavirus (HPV) vaccination of adolescent girls living in communities with elevated cervical cancer rates., Methods: During July to October 2007, we conducted interviews with a probability sample of parents (or guardians) of 10- to 18-year-old girls in five North Carolina counties with cervical cancer rates substantially higher than the national average. Estimates are weighted., Results: We interviewed 889 (73%) of 1220 eligible parents; 38% were black. Overall, 10.3% (95% confidence interval [CI] 7.7%-13.5%) of daughters had received at least 1 dose of HPV vaccine. Only 6.4% of 10- to 12-year-olds had initiated vaccination, versus 17.5% of 16- to 18-year-olds (odds ratio [OR] 3.1, 95% CI 1.4-6.9). Older age of daughters and doctor's recommendation were the only factors independently associated with vaccine initiation. Main reasons reported for not initiating HPV vaccine were: needing more information (22%) or never having heard of the vaccine (14%), believing daughter is too young (16%) or not yet sexually active (13%), and not having gone to the doctor yet (13%). Only 0.5% of parents cited concern about HPV vaccine making a teenage girl more likely to have sex as a main reason for not vaccinating. Of 780 parents with unvaccinated daughters, 62% reported their daughters "probably" or "definitely" will, and 10% reported their daughters "definitely won't" get HPV vaccine in the next year., Conclusions: Approximately 1 year after its introduction, HPV vaccine had been initiated by only 10% of adolescent girls in an area with elevated cervical cancer rates; however, most parents intended for their daughters to be vaccinated. Additional efforts are needed to ensure that parents' intentions to vaccinate are realized.

These recommendations represent the first statement by the Advisory Committee on Immunization Practices (ACIP) on the use of a quadrivalent human papillomavirus (HPV) vaccine licensed by the U.S. Food and Drug Administration on June 8, 2006. This report summarizes the epidemiology of HPV and associated diseases, describes the licensed HPV vaccine, and provides recommendations for its use for vaccination among females aged 9-26 years in the United States. Genital HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year. Although the majority of infections cause no clinical symptoms and are self-limited, persistent infection with oncogenic types can cause cervical cancer in women. HPV infection also is the cause of genital warts and is associated with other anogenital cancers. Cervical cancer rates have decreased in the United States because of widespread use of Papanicolaou testing, which can detect precancerous lesions of the cervix before they develop into cancer; nevertheless, during 2007, an estimated 11,100 new cases will be diagnosed and approximately 3,700 women will die from cervical cancer. In certain countries where cervical cancer screening is not routine, cervical cancer is a common cancer in women. The licensed HPV vaccine is composed of the HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein in yeast using recombinant DNA technology produces noninfectious virus-like particles (VLP) that resemble HPV virions. The quadrivalent HPV vaccine is a mixture of four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant. Clinical trials indicate that the vaccine has high efficacy in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among females who have not already been infected with the respective HPV type. No evidence exists of protection against disease caused by HPV types with which females are infected at the time of vaccination. However, females infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other vaccine HPV types. The vaccine is administered by intramuscular injection, and the recommended schedule is a 3-dose series with the second and third doses administered 2 and 6 months after the first dose. The recommended age for vaccination of females is 11-12 years. Vaccine can be administered as young as age 9 years. Catch-up vaccination is recommended for females aged 13--26 years who have not been previously vaccinated. Vaccination is not a substitute for routine cervical cancer screening, and vaccinated females should have cervical cancer screening as recommended.