9vHPV Types Research Articles

Abstract A112: The seroprevalence of nine human papillomavirus types included in the nonavalent vaccine in unvaccinated women living in Puerto Rico

Abstract Introduction Human papillomavirus (HPV) surveillance is lacking in Puerto Rico (PR). We aim to estimate the seroprevalence of the HPV types included in the nonavalent vaccine (9vHPV) in women and explore associations. Methodology A population-based cross-sectional study of socio-demographic, clinical [including, sexually transmitted infections (STIs)], and behavioral characteristics of sexually active women (16-64 years) was conducted in PR from 2010-2013. Blood samples from 524/566 (92.6%) HPV unvaccinated women were included in this sub- analysis. Antibody responses to 9vHPV types (HPV-6/11/16/18/31/33/45/52/58) were analyzed using M9ELISA by the U.S. Centers for Disease Control and Prevention (CDC). A self-collected cervical and anal sample from all 524 women were also tested using L1 consensus primer (MY09/MY11) PCR followed by dot hybridization to detect 40 HPV types. Statistical analyses included Pearson’s chi-square and logistic regression models. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were reported. Results The mean age of participants was 42.4 years ± 0.6 standard deviations (SD), 52.5% were married/cohabited, and 9.7% were uninsured. About half (51.3%) had between 3-9 lifetime sexual partners, 15.9% had history of STIs, and 40.3% had a current anogenital HPV infection. Overall, 65.8% were seropositive to at least one of the 9vHPV types (1.0% to all 9vHPV types), 59.9% to any of the seven oncogenic types (HPV-16/18/31/33/45/52/58) and 49.1% to any of the quadrivalent vaccine (4vHPV) types. The seroprevalence for specific HPV types ranged between 10.7%-28.1% [HPV-33 (10.7%), 11 (11.6%), 45 (11.8%), 58 (15.8%), 18 (18.7%), 31 (25.0%), 6 (26.2%), 52 (26.9%), and 16 (28.1%)]. In bivariate analysis, significant associations between 9vHPV types were observed with marital status, age at sexual debut, lifetime sexual partners, anal sex, history of STIs and anogenital HPV infection (p<0.05). In the multivariate model, divorced/separated/widowed women (aOR: 2.2, 95%CI: 1.2-4.3) had higher odds of seropositivity to any of the 9vHPV types than single women. Women with 3-9 (aOR: 2.4, 95%CI, 1.5-3.8) and with >10 (aOR: 3.1, 95%CI, 1.6-5.8) lifetime sexual partners had higher odds of seropositivity than women with 1-2 partners. Women with a history of STIs (aOR: 2.1, 95%CI, 1.1-4.0) and with an anogenital HPV infection (aOR: 1.9, 95%CI, 1.2-2.9) had higher odds of HPV seropositivity than their counterparts. In this model, no differences were observed by age, education, healthcare coverage, age at sexual debut or anal sex. Conclusion Before implementation of the HPV nonavalent vaccine, the seroprevalence of at least one of the 9vHPV types among women in PR was high (65.8%). However, less than 1% of women were seropositive for all nine HPV types, indicating this population would benefit from HPV vaccine implementation. Acknowledgements Study funded by the National Institute of Allergy and Infectious Diseases Grant (Grant #1SC2AI090922-01) of the National Institutes of Health. Citation Format: Angeline Cruz, Jeslie M. Ramos-Cartagena, Gitika Panicker, Elizabeth Unger, Ana P Ortiz. The seroprevalence of nine human papillomavirus types included in the nonavalent vaccine in unvaccinated women living in Puerto Rico [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A112.

Immunogenicity of quadrivalent human papillomavirus vaccine among Alaska Native children aged 9–14 years at 5 years after vaccination

BackgroundPersistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. MethodsDuring 2011–2014, we enrolled Alaska Native children aged 9–14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). ResultsAll participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. ConclusionsAlaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination.

Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study.

Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first-void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first-void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type-specific antibody responses to the 9vHPV types were analyzed in 174 first-void urine and 172 serum samples using a virus-like particle-based IgG multiplex enzyme-linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%-100% of first-void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%-100% of first-void urine and 98%-100% of serum samples had HPV-specific antibody concentrations. Results show significant Spearman rank correlations between type-specific HPV-antibody concentrations for paired first-void urine and serum at all time points. This study confirms the potential feasibility of utilizing first-void urine as a noninvasive immunological sample within HPV vaccine trials.

Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer.

In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7-97.7). Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines.

Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018.

Human papillomavirus (HPV) vaccination was introduced in 2006 for females and in 2011 for males. To estimate vaccine impact and effectiveness against quadrivalent HPV vaccine (4vHPV)-type prevalent infection among sexually experienced U.S. females and vaccine effectiveness for sexually experienced U.S. males. NHANES (National Health and Nutrition Examination Survey) conducted in 2003 to 2006 (prevaccine era) and in 2007 to 2010, 2011 to 2014, and 2015 to 2018 (vaccine eras). Nationally representative U.S. surveys. Sexually experienced participants aged 14 to 24 years. U.S. HPV vaccination program. Participant-collected cervicovaginal and penile specimens were tested for HPV DNA. The prevalences of 4vHPV and non-4vHPV types were estimated in each era for females and in 2013 to 2016 for males. Prevalences among the female population overall, vaccinated females, and unvaccinated females were compared in vaccine eras versus the prevaccine era (vaccine impact). Within each vaccine era, prevalence among vaccinated females was compared with that among unvaccinated females (vaccine effectiveness). Vaccine impact and effectiveness were estimated as (1 - prevalence ratio) · 100. Among sexually experienced females aged 14 to 24 years, the impact on 4vHPV-type prevalence in 2015 to 2018 was 85% overall, 90% among vaccinated females, and 74% among unvaccinated females. No significant declines were found in non-4vHPV-type prevalence. Vaccine effectiveness ranged from 60% to 84% during vaccine eras for females and was 51% during 2013 to 2016 for males. Self- or parent-reported vaccination history and small numbers in certain subgroups limited precision. Nationally representative data show increasing impact of the vaccination program and herd protection. Vaccine effectiveness estimates will be increasingly affected by herd effects. Centers for Disease Control and Prevention.

Sexual Positioning Practices and Anal Human Papillomavirus Infection Among Young Men Who Have Sex with Men and Transgender Women-Chicago, Illinois, 2016-2018.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States; men who have sex with men (MSM) have higher prevalence of infection and related disease compared with other men. We assessed whether differences in HPV acquisition exist among MSM according to their sexual positioning practices, as well as self-reported receipt of HPV vaccination. We enrolled young MSM and transgender women aged 18 to 26 years in Chicago, IL (N = 666). Participants self-reported their history of HPV vaccination and submitted self-collected anal swab specimens for type-specific HPV detection using an L1-consensus PCR assay. Multivariable logistic regression analyses were used to assess relationships between sexual positioning practices and detection of any HPV or quadrivalent HPV vaccine (4vHPV) types by vaccination status, defined as self-reported receipt of ≥1 HPV vaccine dose versus none. Among 666 participants, 400 (60.1%) had any anal HPV, and 146 (21.9%) had a 4vHPV type. Among vaccinated participants, 18, 36, and 177 reported exclusively insertive, exclusively receptive, or both sexual positioning practices, respectively. Compared with participants reporting exclusively insertive anal sex, odds of any HPV were significantly higher among participants engaging exclusively in receptive anal sex (adjusted odds ratio [aOR], 5.90; 95% confidence interval [CI], 2.52-13.78), as well as those engaging in both (aOR, 3.32; 95% CI, 1.71-6.44). Vaccinated participants, compared with unvaccinated participants, had lower odds of 4vHPV-type HPV regardless of sexual positioning practices (aOR, 0.56; 95% CI, 0.34-0.92). Adult men and transgender women who practice anal receptive sex have high prevalence of infection with any HPV. Routine vaccination of all adolescents is expected to reduce HPV-related disease incidence among adult MSM and transgender women as vaccinated cohorts age.

Prevalence of Oral Human Papillomavirus Infection: Impact of Sex, Race/Ethnicity, and Vaccination Status.

Prior studies have demonstrated differences in oral human papillomavirus (HPV) prevalence by sex and race/ethnicity. In this study, we examined the impact of vaccination on these disparities. We examined participants aged 18-59 years in the National Health and Nutrition Examination Survey from 2011 to 2016 who reported their HPV vaccination status and submitted an adequate oral sample (N = 9437). Oral prevalence of HPV, grouped by any, low-risk, high-risk, 4 valent (4v) HPV, 9 valent (9v) HPV, and nonvaccine types, was examined by sex, race/ethnicity, and vaccination status. Binary logistic regression was used to estimate prevalence ratios by vaccination status. Multivariable logistic regression models controlled for age, sex, and race/ethnicity. The prevalence of any, nonvaccine, low-risk, high-risk, 4vHPV, and 9vHPV types was higher among males than females, even among vaccinated participants. Examination of racial/ethnic differences demonstrated differences in all HPV groups among unvaccinated males and among low-risk types in females. In all but the 2 vaccine-type groups, the prevalence of oral HPV was notably higher among Black males compared with other groups. Significant differences were not observed by race/ethnicity among vaccinated males or females. Males tested positive for oral HPV more frequently than females, even among those vaccinated. This may have resulted from a lower frequency of males being vaccinated before initiating oral sex than females. Vaccination of males at the recommended age, therefore, may decrease differences in oral HPV by sex. Racial/ethnic differences were observed only in unvaccinated individuals, suggesting these disparities will decrease as more individuals are vaccinated.

Prevalence of Genital Human Papillomavirus by Age and Race/Ethnicity Among Males.

Genital and oral cancers are often caused by human papillomavirus (HPV) types that can be prevented through HPV vaccination. Since HPV is sexually transmitted, knowledge of penile prevalence of vaccine-type HPV among US males can help predict potential disparities in these cancers. This study examines penile HPV prevalence by age and race/ethnicity among males. This study was a secondary analysis of publicly available data from the National Health and Nutrition Examination Survey (NHANES). Using data from penile swab samples collected from males between 2013 and 2016, the prevalence of 4vHPV and 9vHPV vaccine types was examined across age groups and by race/ethnicity. Logistic regression models adjusting for demographics, sexual behavior, and circumcision were examined to determine whether associations remained after accounting for confounders. Among 2548 males evaluated, HPV infection prevalence differed by race/ethnicity, with Black males exhibiting a higher prevalence of HPV. Examination of 4vHPV type prevalence by age group showed that 18-26-year-old males had a lower prevalence than older age groups. After controlling for confounders, 4vHPV prevalence was only significantly elevated among 27-34-year-old males, those who were single, and males with ≥3 lifetime sex partners. In adjusted models, 9vHPV type prevalence remained elevated among Black males compared with White males. Variations in 9vHPV type prevalence between Black and White individuals indicate future disparities in HPV-related genital cancers may continue in the United States during the next decade. Revaccinating certain populations with the 9vHPV vaccine may be appropriate to help mitigate this.

Declines in Prevalence of Human Papillomavirus Vaccine-Type Infection Among Females after Introduction of Vaccine - United States, 2003-2018.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (1). Although most infections resolve without clinical sequalae, persistent HPV infection can cause cervical, other anogenital, and oropharyngeal cancers and anogenital warts. HPV vaccination has been recommended in the United States at age 11-12 years since 2006 for females and since 2011 for males. Catch-up vaccination is recommended through age 26 years.* A quadrivalent vaccine (4vHPV) targeting types 6, 11, 16, and 18 was mainly used until 2015, when a 9-valent vaccine (9vHPV), targeting the same four types as 4vHPV and five additional types (31, 33, 45, 52, and 58), was introduced; 9vHPV has been the only vaccine available in the United States since the end of 2016 (2). HPV vaccination coverage has increased but remains lower than that of other vaccinations recommended for adolescents (3). A decrease in prevalence of 4vHPV types detected in cervicovaginal swabs among young females from the prevaccine era (2003-2006) to 2007-2010 in the National Health and Nutrition Examination Survey (NHANES) was an early indicator of vaccine impact (2) and was also observed in later periods (4,5). NHANES data from 2017-2018 were included in this analysis to update HPV prevalence estimates among females aged 14-34 years. From the prevaccine era to 2015-2018, significant decreases in 4vHPV-type prevalence occurred among females aged 14-19 years (88%) and 20-24 years (81%). In sexually experienced females, 4vHPV-type prevalence decreased in those who reported receiving ≥1 HPV vaccine dose (97% among those aged 14-19 years, 86% among those aged 20-24 years) and in those who reported no vaccination (87% among those aged 14-19 years, 65% among those aged 20-24 years). Significant declines among unvaccinated females suggest herd effects. These data show increasing impact of HPV vaccination in the United States. HPV vaccination is a critical prevention tool against HPV infection, anogenital warts, and HPV-attributable precancers and cancers. HPV vaccination is highly effective and is recommended routinely at age 11-12 years and through 26 years for persons not already vaccinated.

Immunogenicity and Safety of the 9-Valent Human Papillomavirus Vaccine in Solid Organ Transplant Recipients and Adults Infected With Human Immunodeficiency Virus (HIV).

The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.

A prospective cohort study of immunogenicity of quadrivalent human papillomavirus vaccination among Alaska Native Children, Alaska, United States

ObjectiveIn the United States, HPV vaccination is routinely recommended at age 11 or 12 years; the series can be started at age 9. We conducted a cohort study to assess long-term immunogenicity of quadrivalent HPV vaccine (4vHPV) in an American Indian/Alaska Native (AI/AN) Indigenous population. MethodsDuring 2011–2014, we enrolled AI/AN girls and boys aged 9–14 years, who were vaccinated with a 3-dose series of 4vHPV. Serum specimens were collected at five time points: immediately prior to doses 2 and 3, and at one month, one year, and two years after series completion. Antibody testing was performed using a multiplex virus-like-particle-IgG ELISA for 4vHPV types (HPV 6/11/16/18). ResultsAmong 477 children (405 girls/72 boys) completing the 3-dose series, median age at enrollment was 11.2 years. Of the 477, 72 (15%) were tested before dose 2 and 70 (15%) before dose 3. Following series completion, 435 (91%) were tested at one month, 382 (80%) at one year, and 351 (74%) at two years. All tested participants had detectable antibody to 4vHPV types at all time points measured. Geometric mean concentrations (GMCs) for 4vHPV types at one month and two years post-series completion were 269.9 and 32.7 AU/ml for HPV6, 349.3 and 42.9 AU/ml for HPV11, 1240.2 and 168.3 IU/ml HPV16, and 493.2 and 52.2 IU/ml for HPV18. Among children tested after each dose, GMCs after doses 1 and 2 were 3.9 and 32.2 AU/ml for HPV6, 5.3 and 45.6 AU/ml for HPV11, 20.8 and 187.9 IU/ml for HPV16; and 6.6 and 49.7 IU/ml for HPV18. No serious adverse events were reported. ConclusionAll AI/AN children developed antibodies to all 4vHPV types after vaccination. GMCs rose after each dose, then decreased to a plateau over the subsequent two years. This cohort will continue to be followed to determine duration of antibody response.

Prevalence, incidence, and natural history of HPV infection in adult women ages 24 to 45 participating in a vaccine trial

ObjectivesThe natural history of human papillomavirus (HPV) infection has been studied extensively in young women; this study investigated HPV infection in adult women. MethodsData from 3817 women aged 24–45 years in a global trial of the 4-valent HPV (6/11/16/18) vaccine were used to calculate prevalence of anogenital infections containing 9-valent (9v) HPV vaccine types (6/11/16/18/31/33/45/52/58) and five non-vaccine types (35/39/51/56/59). Incidence of infections and persistent infections was estimated for 989 placebo recipients naive to all 14 HPV types at baseline. Age-adjusted hazard ratios were calculated for various sociodemographic factors. ResultsPrevalence of anogenital infection was highest in France at 29.2% (9vHPV types) and 21.7% (non-vaccine types) and lowest in the Philippines at 7.6% (9vHPV types) and 5.1% (non-vaccine types). Overall, HPV incidence (per 100 person-years) was 5.2 (9vHPV types) and 4.7 (non-vaccine types), and incidence of persistent infection was 2.7 (9vHPV types) and 2.1 (non-vaccine types). Factors associated with new HPV infections included younger age, younger age at first intercourse, being single, current use of tobacco, and higher number of past and recent sex partners. ConclusionsBecause mid-adult women acquire new HPV infections, administration of the 9vHPV vaccine could reduce HPV-related morbidity and mortality in this population.

Human Papillomavirus Vaccine Effectiveness Against HPV Infection: Evaluation of One, Two, and Three Doses.

Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses. We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses. Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12). Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses.

Vaccine-preventable anal infections by human papillomavirus among HIV-infected men who have sex with men.

HIV-infected men who have sex with men (MSM) show the highest prevalence of anal HPV infection. Anal prevalence of the HPVs targeted by the quadrivalent HPV vaccine (4vHPV) and nonavalent HPV vaccine (9vHPV)was estimated in this population. Anal specimens were collected from HIV-infected MSM attending a sexually transmitted infection/HIV center. Specimens were analyzed using the Linear Array HPV Genotyping Test. A total of 49.5and 71.2% of the 313 enrolled MSM harbored at least one of the 4vHPV and 9vHPV types, respectively. A significantly decreasing trend was observed for the prevalence of both 4vHPV (p=0.04) and 9vHPV types (p<0.001) across age classes. A substantial proportion of HIV-infected MSM do not harbor a current anal infection with vaccine-preventable HPVs. The potential benefit of the 4vHPV versus 9vHPV vaccination in these subjects, including older MSM, should be investigated.

Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals

BackgroundThe originally recommended dosing schedule, 0, 2, 6 months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. MethodsThis multi-site, prospective study enrolled healthy 9–17 year old girls (n = 1321) on the day of or within 28 days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. ResultsCompared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants ≥15 years old had no difference in post-dose 2 titers compared to <15 year olds when dose 2 was substantially delayed. ConclusionsProlonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV.ClinicalTrials.gov (NCT00524745).

Cervical Adenocarcinoma in Situ in the United States: Results from Population-based Laboratory Surveillance, 2008–2014

BackgroundCervical cancer screening methods are more effective for detection of squamous cell carcinoma precursor lesions (cervical intraepithelial neoplasia; CIN2 and 3) than for less-common adenocarcinoma precursors (adenocarcinoma in situ; AIS). Primary prevention through human papillomavirus (HPV) vaccination is expected to impact both CIN and AIS, although less data exist about the HPV types associated with AIS. We analyzed HPV types detected in AIS and CIN identified through population-based surveillance.MethodsThe Centers for Disease Control and Prevention and partners conduct surveillance for CIN2, CIN3, and AIS (CIN2+) among women aged ≥18 years in five locations in the United States. Specimen blocks for women aged 18–39 are sent to CDC for HPV typing using L1 consensus PCR. We analyzed cases with AIS only, AIS with CIN2 or 3 (AIS+CIN), and CIN3 only, the highest grade squamous cell precursor. We used chi-square tests to compare HPV types by histology. Types evaluated were HPV16 and 18 (high-risk (HR) types targeted by all HPV vaccines), 5 additional HR types targeted by the 9-valent vaccine (31/33/45/52/58; “additional 9vHPV”), and 7 other HR non-vaccine types (35/39/51/56/59/66/68).ResultsBetween 2008 and 2014, 18,394 women were diagnosed with CIN2+. Of those, 517 (2.8%) had AIS (283 AIS only, 234 AIS+CIN) and 5,766 (31%) had CIN3 only. Median ages at diagnosis for AIS, AIS+CIN, and CIN3 were 37, 32, and 31 years, respectively. HPV typing results were available for 89 AIS, 99 AIS+CIN, and 2,923 CIN3 cases; HPV was detected in nearly all specimens (99% AIS, 100% AIS+CIN, 98% CIN3), and 21% of positive specimens had >1 HPV type identified. HPV16 (AIS: 51%, AIS+CIN: 64%, CIN3: 59%; p ≤ 0.001) and HPV18 (AIS: 39%, AIS+CIN: 31%, CIN3: 5%; P ≤ 0.001) were most common. Additional 9vHPV types (AIS: 3%, AIS+CIN: 12%, CIN3: 26%; P ≤ 0.001), and HR non-vaccine types (AIS: 6%, AIS+CIN2+: 2%, CIN3+: 9%; P ≤ 0.001) were detected less frequently.ConclusionHPV types differed by histology, with AIS having a greater proportion of HPV 18 and a lower proportion of additional 9vHPV and HR non-vaccine types. This report on the largest sample of genotyped AIS cases to date provides data for vaccine impact monitoring, and suggests a high opportunity for vaccine prevention of AIS.Disclosures M. R. Griffin, MedImmune: Grant Investigator, Grant recipient

Cutaneous HPV and alpha-mucosal 9-valent HPV sero-status associations

Seroepidemiology of human papillomaviruses (HPV) among men is poorly understood. We examined the association between seropositivity to cutaneous HPV and 9-valent HPV (9vHPV) types. Six hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens were tested for antibodies against 9vHPV types [low-risk (6/11) and high-risk (16/18/31/33/45/52/58)], and 14 cutaneous types, including β-types 5/8/12/14/17/22/23/24/38/47, α-type-27, γ-type-4, µ-type-1, and ν-type-41, using a GST L1-based multiplex serology assay. Risk factor data were collected through questionnaires. Logistic regression was used to evaluate associations between mucosal and cutaneous HPV types. Approximately 21% of men were positive for ≥ 1 cutaneous HPV type, and ≥ 1 nine-valent HPV vaccine type at the same time. Men who were seropositive for any-cutaneous HPV were nearly twice as likely to be seropositive for 9vHPV (adjusted odds ratio (AOR) = 1.97, 95% confidence interval (CI): 1.30–2.99), high-risk (AOR = 1.83; 95% CI: 1.04–3.20), low-risk (AOR = 1.92; 95% CI: 1.16–3.18), and four-valent, 4vHPV, (AOR = 2.01; 95% CI: 1.25–3.21). Type-specific cutaneous HPV seropositivity (types: 8/14/17/23/38/27/4/1) was also positively associated with seropositivity to 9vHPV, high-risk, and low-risk categories. These data indicate that exposure to cutaneous HPV and 9vHPV types is common. Future longitudinal studies are needed to assess the temporality of these associations.

Prevalence of Genital Human Papillomavirus in Males, United States, 2013-2014.

We report the first nationally representative prevalence data on genital human papillomavirus (HPV) in males in the United States, using findings from the National Health and Nutrition Examination Surveys, 2013-2014. Using penile swabs from males aged 14-59 years, we estimated the HPV DNA prevalence and prevalence ratios (PRs) with respect to sexual behaviors and demographic characteristics. The prevalence of any HPV was 42.2% (95% confidence interval [CI], 38.3%-46.1%) and of high-risk (HR) HPV was 23.4% (95% CI, 21.3%-25.6%). Prevalence of any HPV was 12.5% in 14-19 year olds and was higher in older age groups, through ages 25-29 years, and then similar through age 59 years. After adjustment for age and race, any HPV prevalence was associated with lifetime number of sex partners (≥15 vs 1-2; PR, 3.27; 95% CI, 2.12-5.02) and past-year number of sex partners (≥2 vs 0; PR, 1.26; 95% CI, 1.09-1.46). Comparisons of consecutively older age groups revealed that the prevalence of quadrivalent HPV vaccine types (4vHPV), types 6, 11, 16, and 18, was significantly higher only between ages 25-29 and 20-24 years (PR, 2.79; 95% CI, 1.31-5.96), whereas the prevalence of other HPV types was significantly higher only between ages 20-24 and 14-19 years (PR, 3.39; 95% CI, 2.49-4.61). Overall, 42.2% of US males aged 14-59 years have detectable genital HPV infections. Differences in the age-specific prevalence of 4vHPV types and non-4vHPV types suggest that the vaccination program has had an impact on the prevalence of HPV types 6, 11, 16, and 18 among males.

Seroprevalence and Associated Factors of 9-Valent Human Papillomavirus (HPV) Types among Men in the Multinational HIM Study

BackgroundHuman papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Recently a 9-valent HPV (9vHPV) prophylactic vaccine was licensed. Seroprevalence prior to vaccine dissemination is needed for monitoring vaccine effectiveness over time. Few studies have assessed the seroprevalence of 9vHPV types in men.ObjectivesTo investigate the seroprevalence of 9vHPV vaccine types and associated risk factors among men residing in Brazil, Mexico, and the United States.MethodsSix hundred men were randomly selected from the HPV Infection in Men (HIM) Study. Archived serum specimens collected at enrollment were tested for antibodies against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52 and 58) using a glutathione S-transferase (GST) L1-based multiplex serologic assay. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire. Binomial proportions were used to estimate seroprevalence and logistic regression was used to examine factors associated with seropositivity of type-specific and grouped (i.e. 9vHPV, high-risk 9vHPV, low risk 9vHPV, and five-additional) HPV types.ResultsOverall, 28.3% of men were seropositive for at least one of the 9vHPV vaccine types, 14.0% for at least one of the seven high-risk types (16, 18, 31, 33, 45, 52 and 58) and 11.2% for at least one of the five high-risk types (31, 33, 45, 52 and 58) not included in the quadrivalent HPV vaccine, and 17.4% for at least one of the low-risk types (6/11). In multivariate analyses, odds ratios adjusted (AOR) for country of residence, age, marital status, smoking, number of anal sex lifetime partners, compared to men with no anal sex lifetime partners, men with ≥2 partners were more likely to be seropositive for grouped HPV [(9vHPV: AOR 2.52; 95% confidence interval (CI) 1.40–4.54), (high-risk 9vHPV: AOR 2.18; 95%CI: 1.05–4.50) and (low-risk 9vHPV: AOR 2.12; 95%CI: 1.12–4.03)], and individual HPV types 6, 16, 33 and 58 with AORs ranging from 2.19 to 7.36. Compared to men aged 18–30 years, men older than 30 years were significantly more likely to be seropositive for any high-risk 9vHPV, in addition to individual types 18 and 45; and compared to never smokers, current smokers were more likely to be seropositive to 9vHPV, low-risk 9vHPV and HPV 6. In contrast, married men were less likely to be seropositive to any high-risk 9vHPV and individual HPV types 18 and 31 when compared to single men.ConclusionsThese data indicate that exposure to the nine HPV types included in the 9vHPV vaccine is common in men and that seropositivity to 9vHPV vaccine types is associated with older age and the lifetime number of anal sex partners. Nine valent HPV vaccination of males and females has the potential to prevent HPV related diseases and transmission in both sexes.

Prevalence of 9-Valent Human Papillomavirus Types by Race/Ethnicity in the Prevaccine Era, United States, 2003-2006.

Before any vaccine introduction, overall DNA prevalence of any 9-valent human papillomavirus (9vHPV) types, HPV 31/33/45/52/58, and HPV 16/18 was 16.0%, 9.5%, and 6.2%, respectively, among female participants in National Health and Nutrition Examination Survey. Non-Hispanic black females were more likely to have infection with HPV 31/33/45/52/58, but not HPV 16/18, compared to non-Hispanic white females.