Primary care provider practices and beliefs related to cervical cancer screening with the HPV test in Federally Qualified Health Centers

Objective

Cervical cancer screening using the human papillomavirus (HPV) test and Pap test together (co-testing) is an option for average-risk women ≥ 30 years of age. With normal co-test results, screening intervals can be extended. The study objective is to assess primary care provider practices, beliefs, facilitators and barriers to using the co-test and extending screening intervals among low-income women.

Method

Data were collected from 98 providers in 15 Federally Qualified Health Center (FQHC) clinics in Illinois between August 2009 and March 2010 using a cross-sectional survey.

Results

39% of providers reported using the co-test, and 25% would recommend a three-year screening interval for women with normal co-test results. Providers perceived greater encouragement for co-testing than for extending screening intervals with a normal co-test result. Barriers to extending screening intervals included concerns about patients not returning annually for other screening tests (77%), patient concerns about missing cancer (62%), and liability (52%).

Conclusion

Among FQHC providers in Illinois, few administered the co-test for screening and recommended appropriate intervals, possibly due to concerns over loss to follow-up and liability. Education regarding harms of too-frequent screening and false positives may be necessary to balance barriers to extending screening intervals.     

Knowledge and intention to participate in cervical cancer screening after the human papillomavirus vaccine

Background

If women who receive the human papillomavirus (HPV) vaccine are unduly reassured about the cancer prevention benefits of vaccination, they may choose not to participate in screening, thereby increasing their risk for cervical cancer. This study assesses adult women's knowledge of the need to continue cervical cancer screening after HPV vaccination, describes Pap test intentions of vaccinated young adult women, and evaluates whether knowledge and intentions differ across groups at greatest risk for cervical cancer.

Methods

Data were from the 2008 Health Information National Trends Survey (HINTS) and the 2008 National Health Interview Survey (NHIS), which initiated data collection approximately 18 months after the first FDA approval of an HPV vaccine. We calculated associations between independent variables and the outcomes using chi-square tests.

Results

Of 1586 female HINTS respondents ages 18 through 74, 95.6% knew that HPV-vaccinated women should continue to receive Pap tests. This knowledge did not vary significantly by race/ethnicity, education, income, or healthcare access. Among 1101 female NHIS respondents ages 18-26 who had ever received a Pap test, the proportion (12.7%; n = 139) who reported receipt of the HPV vaccine were more likely than those not vaccinated to plan to receive a Pap test within three years (98.1% vs. 92.5%, p < 0.001).

Conclusions

US adult women possess high knowledge and intention to participate in Pap testing after HPV vaccination. The vast majority of young adult women who received the HPV vaccine within its first two years on the market intend to participate in cervical cancer screening in the near future. Future studies are needed to examine whether those vaccinated in adolescence will become aware of, and adhere to, screening guidelines as they become eligible.     

Decline in prevalence of human papillomavirus infection following vaccination among Australian Indigenous women,a population at higher risk of cervical cancer: The VIP-I study

BackgroundCervical cancer occurrence and mortality are strongly correlated with socioeconomic disadvantage, largely due to unequal access to screening and treatment. Universal human papillomavirus (HPV) vaccination provides the opportunity to greatly reduce this global health disparity. Australian Indigenous women have substantially higher rates of cervical cancer than non-Indigenous women, primarily due to under-screening. We investigated HPV infection rates in Indigenous women 7 years after implementation of the national HPV vaccination program.MethodsWe used a repeat cross-sectional design, with the baseline being provided by an HPV prevalence survey among Indigenous women attending clinics for cervical cytology screening, prior to the start of the vaccination program in 2007. We returned to clinics in four locations during 2014–15, and invited women aged 18–26 years attending for screening to provide a cervical specimen for HPV testing, as well as to complete a short questionnaire and consent to allow access of their records in the National HPV Vaccination Program Register. We used well-established laboratory methods to test specimens for specific HPV genotypes.ResultsA total of 142 women were recruited at participating sites and compared to 155 who had been recruited at the same locations in the 2007 pre-vaccine survey. The two groups were identical in regard to age, with the more recent group having a higher proportion of hormonal contraception users, and a lower proportion of smokers. The proportion found to have any HPV type fell from 58 to 36% with the decline being entirely due to reductions in vaccine types, which fell by 94% from 24 to 1.4%.ConclusionAustralia’s national HPV vaccination program appears to be successfully protecting a very high proportion of Indigenous women against vaccine targeted HPV types, who have in the past been at elevated risk of cervical cancer.     

Monitoring the impact of human papillomavirus vaccines on high-grade pre-invasive cervical lesions: Designing a framework of linked immunization information system and cancer registry data in Michigan

State immunization and cancer registries contain data that, if linked, could be used to monitor the impact of human papillomavirus (HPV) vaccine on cervical cancer and precancer. Michigan is uniquely positioned to examine these outcomes using two population-based resources: the state-wide cancer registry and immunization information system (IIS).We assessed the feasibility of identifying females in the IIS who had continuous Michigan residence and linking them to the cancer registry. We considered continuous residence necessary for future studies of vaccine impact to avoid misclassifying those who may have been immunized while residing out-of-state and whose immunization therefore may not have been reported in Michigan.We identified females with 1976–1996 birthdates in the IIS and used probabilistic linkage software to match them with Michigan birth records. A stratified random sample of IIS-birth matches was provided to a commercial locator service to identify females with continuous Michigan residence. Cervical carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years were also matched with the birth records; cancer registry-birth matches were merged with the IIS-birth matches using the birth record identifier.Overall, 68% of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched with birth records. Among the sample of IIS-birth matches, most (86%) were continuous residents. Seventy percent or more of cancer registry-birth matches merged with IIS-birth matches for cases born after 1984.This is the first effort in the U.S. to show that linking records across IIS and cancer registries is practical and reasonably efficient. The increasing proportion of matches between the registries and live birth file with birth year, and the use of population-based data, strengthen the utility of this approach. Future steps include use of this method to examine incidence of cervical cancer precursors in HPV immunization-eligible females.     

Evaluating associations between sources of information, knowledge of the human papillomavirus, and human papillomavirus vaccine uptake for adult women in California

Objective

Vaccines have the potential to reduce morbidity from HPV infections if age-eligible patients receive and parents know about them. Content analyses have demonstrated significant range in the quality of HPV information obtained from different sources. The purpose of this study was to determine the pattern of associations between information source and level of knowledge about HPV and vaccine receipt/intention.

Methods

We analyzed the 2007 California Health Interview Survey, a population-based, statewide random digit dial survey, using data on adult females ages 18–65 who had heard about HPV (n = 16,806). One-way ANOVA and multivariate logistic regression assessed the associations between source of information (advertisement only, advertisement plus other sources, and non-advertisement sources) and knowledge of HPV (3 or greater correct on a 4-point scale). Multivariate logistic regressions were conducted on a subsample of vaccine-eligible women and parents to assess vaccine uptake or intention.

Results

Less than half of respondents (43%) correctly answered 3 or more of the HPV knowledge questions. Mean knowledge scores were significantly different when comparing women who reported advertisement only, non-advertisement, and advertisement plus other sources of information (p < 0.001). In multivariate analysis, women who reported non-advertisement sources (OR 2.44, 95% CI 2.07–2.87) and advertisements plus other sources (OR 3.03, 95% CI 2.57–3.58) were more likely to have knowledge scores above the 75% level than women who relied on advertisements alone. In the subsample of vaccine-eligible women and parents, those who reported advertisements plus other sources (OR 1.85, 95% CI 1.30–2.62) were more likely to have received or intend to receive the vaccine than those who reported advertisements as their sole information source.

Conclusion

Advertisements are the most commonly reported source of information about HPV, and while they inform women of the existence of the vaccine, they do not contribute to accurate knowledge about the virus, nor do they appear to influence vaccine uptake. Other sources may play a larger role in refining knowledge and/or improving uptake.     

Preparing for HPV vaccination in South Africa: key challenges and opinions

This article reports on qualitative research investigating key challenges and barriers towards human papillomavirus (HPV) vaccine introduction in the Western Cape Province, South Africa. A total of 50 in-depth interviews and 6 focus groups were conducted at policy, health service and community levels of enquiry. Respondents expressed overall support for the HPV vaccine, underscored by difficulties associated with the current cervical screening programmes and the burgeoning HIV/AIDS epidemic in South Africa. Overall poor community knowledge of cervical cancer and the causal relationship between HPV and cervical cancer suggests the need for continued education around the importance of regular cervical screening. The optimal target populations for HPV vaccination was influenced by the perceived median age of sexual activity in South African girls (9-15 years), with an underlying concern that high levels of sexual abuse had significantly decreased the age of sexual exposure suggesting vaccination should commence as early as 9 years. Vaccination through schools with the involvement of other stakeholders such as sexual and reproductive health and the advanced programme on immunization (EPI) were suggested. Opposition to the HPV vaccine was not anticipated if the vaccine was marketed as preventing cervical cancer rather than a sexually transmitted infection. The findings assist in identifying potential barriers and facilitating factors towards HPV vaccines and will inform the development of policy and programs to support HPV vaccination introduction in South Africa and other African countries.     

Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: A transmission-dynamic modelling study

Background

Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost-effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada.

Methods

We used HPV-ADVISE, an individual-based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost.

Findings

Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)-gained varying between $7900–24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated.

Interpretation

Two-dose HPV vaccination is likely to be cost-effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls.     

Impact of reduced human papillomavirus vaccination coverage rates due to COVID-19 in the United States: A model based analysis

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected utilization of preventative health care, including vaccines. We aimed to assess HPV vaccination rates during the pandemic, and conduct a simulation model-based analysis to estimate the impact of current coverage and future pandemic recovery scenarios on disease outcomes. The model population included females and males of all ages in the US. The model compares pre-COVID vaccine uptake to 3 reduced coverage scenarios with varying recovery speed. Vaccine coverage was obtained from Truven Marketscan™. Substantially reduced coverage between March-August 2020 was observed compared to 2018–2019. The model predicted that 130,853 to 213,926 additional cases of genital warts; 22,503 to 48,157 cases of CIN1; 48,682 to 110,192 cases of CIN2/3; and 2,882 to 6,487 cases of cervical cancer will occur over the next 100 years, compared to status quo. Providers should plan efforts to recover HPV vaccination and minimize potential long-term consequences.     

An update on human papillomavirus vaccine uptake among 11-17 year old girls in the United States: National Health Interview Survey, 2010

Purpose

A 3-dose human papillomavirus (HPV) vaccine is recommended for adolescents to protect against HPV-related cervical and other cancers. The purpose of this study was to provide an update on HPV vaccine uptake among 11–17 year old girls residing in the US.

Methods

Data from the 2010 National Health Interview Survey (NHIS) were obtained to assess HPV vaccination status and its correlates. Multivariate logistic regression analyses were performed to examine HPV vaccine uptake of ≥1 dose and ≥3 doses among all girls, and completion of the 3-dose series among those who initiated (received ≥1 dose) the vaccine.

Results

Overall, 28.9% and 14.2% received ≥1 dose and ≥3 doses of vaccine: 14.5% and 3.0% among 11–12 year old girls, and 34.8% and 18.7% among 13–17 year olds, respectively. Hispanics had higher uptake of ≥1 dose (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.22–2.17) than whites. Having received an influenza shot in the past year and parents’ awareness of the vaccine were significantly associated with receiving ≥1 dose (OR 1.88, 95% CI 1.51–2.33 and OR 16.57, 95% CI 10.95–25.06) and ≥3 doses (OR 1.48, 95% CI 1.13–1.92 and OR 10.60, 95% CI 5.95–18.88). A separate multivariate model based on girls who initiated the vaccine did not identify any significant correlates of 3-dose series completion. Among parents of unvaccinated girls, 60% were not interested in vaccinating their daughters and mentioned three main reasons: “does not need vaccine” (25.5%), “worried about safety” (19.3%) and “does not know enough about vaccine” (16.6%). Of those who were interested, 53.7% would pay $360–$500 for the vaccination, while 41.7% preferred to receive it at a much lower cost or free.

Conclusions

Only 1 out of 3 girls (11–17 years) have received ≥1 dose of HPV vaccine and much less have completed all 3 doses. Strategies should be taken to improve this vaccine uptake among girls, especially those 11–12 year olds, and to educate parents about the importance of vaccination.     

Implementation of the Standards for adult immunization practice: A survey of U.S. Health care providers

The revised Standards for Adult Immunization Practice (“Standards”), published in 2014, recommend routine vaccination assessment, strong provider recommendation, vaccine administration or referral, and documentation of vaccines administered into immunization information systems (IIS). We assessed clinician and pharmacist implementation of the Standards in the United States from 2016 to 2018. Participating clinicians (family and internal medicine physicians, obstetricians-gynecologists, specialty physicians, physician assistants, and nurse practitioners) and pharmacists responded using an internet panel survey. Weighted proportion of clinicians and pharmacists reporting full implementation of each component of the Standards were calculated. Adjusted prevalence ratio (APR) estimates of practice characteristics associated with self-reported implementation of the Standards are also presented. Across all medical specialties, the percentages of clinicians and pharmacists implementing the vaccine assessment and recommendation components of the Standards were >80.0%. However, due to low IIS documentation, full implementation of the Standards was low overall, ranging from 30.4% for specialty medicine to 45.8% in family medicine clinicians. The presence of an immunization champion (APR, 1.40 [95% confidence interval {CI}, 1.26 to 1.54]), use of standing orders (APR, 1.41 [95% CI, 1.27 to 1.57]), and use of a patient reminder-recall system (APR, 1.39 [95% CI, 1.26 to 1.54]) were positively associated with adherence to the Standards by clinicians. Similar results were observed for pharmacists.Nonetheless, vaccination improvement strategies, i.e., having standing orders in place, empowering an immunization champion, and using patient recall-reminder systems were underutilized in clinical settings; full implementation of the Standards was inconsistent across all health care provider practices.     

Design and content validation of a survey questionnaire assessing the determinants of human papillomavirus (HPV) vaccine hesitancy in France: A reactive Delphi study

IntroductionThis study aimed to develop and undertake a preliminary validation of a French Survey Questionnaire for the Determinants of HPV Vaccine Hesitancy (FSQD-HPVH).MethodsWe undertook an electronic-based Delphi consultation among a panel of Francophone experts in two rounds. Round 1 consisted of the assessment of a structured questionnaire comprising of three parts ((i) Contextual influences, (ii) Individual and group influences, and (iii) Vaccine/vaccination-specific issues), in line with the WHO Strategic Advisory Group of Experts (SAGE) Vaccine Hesitancy (VH) Model of Determinants. Items included in this questionnaire were based on a literature review. Definitions of the factors included in the SAGE model were provided in the questionnaire. The panel of experts was asked to score each item using a 3-point Likert scale, in which 1 meant “Essential”, 2 “Useful but not essential”, and 3 “Not necessary”. The panel was also invited to comment on the clarity/comprehension of the questions and suggest reformulations/additional items. Lawshe's Content Validity Ratio (CVR) was computed to assess the level of consensus for each statement. Only items upon which agreement was not reached in Round 1 (CVR < 0.6) and newly proposed items were submitted for evaluation in Round 2, using the same procedure.ResultsFifteen experts completed the two rounds. Of 83 items evaluated in Round 1, 35 (42%) had a CVR ≥ 0.6 and were accepted without modification. In Round 2, 66 items were submitted to the same panel and consensus was reached for 22 (33%) items using the threshold of 0.6. The final FSQD-HPVH version includes 57 items.ConclusionThis study developed a survey instrument for the evaluation of HPV VH in France with good content validity. It will be used to assess the determinants of HPV VH, the first step towards an evidence-based approach to improving HPV vaccination rates in France.     

Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: A partially-blind randomised placebo-controlled study

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18–25 years (N = 120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix^®; GlaxoSmithKline Vaccines) or placebo (Al[OH]₃) at 0, 1 and 6 months (double-blind). HIV-negative women (N = 30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection.     

Association between human papillomavirus vaccine status and sexually transmitted infection outcomes among females aged 18-35 with a history of sexual activity in the United States: A population survey-based cross-sectional analysis

BackgroundCurrent human papillomavirus (HPV) vaccine coverage in the United States (in 2019, 66–70%), remains below the Healthy People 2020 coverage goal of 80%. HPV vaccine misinformation, including parental concerns of sexual risk-compensation influence vaccine uptake. We examined the association between HPV vaccination and sexually transmitted infection (STI) outcomes.MethodsOf the 20,146 participants from 2013 to 2014 and 2015–2016 cycles of the National Health and Nutrition Examination Survey, 1050 females aged 18–35 with a history of sexual activity had complete case data. Roa-Scott Chi-squared and F-tests assessed survey-weighted socio-demographic differences between vaccinated and unvaccinated participants. Weighted logistic regression assessed crude and adjusted associations between self-reported HPV vaccination (none vs. ≥ 1dose) and lab-confirmed STIs (trichomonas and chlamydia) and vaccine-type HPV (6/11/16/18). As a sensitivity analysis, we conducted weighted-propensity score (PS) models and inverse probability weighting by vaccination status. PS and logistic regression were estimated through survey-weighted logistic regression on variables including race, education, income, marital status, US citizenship, cycle year and age.ResultsOverall, 325 (31.8%) females with a history of sexual activity were HPV vaccinated, of which 22 (6.1%) received the vaccine at the routine-recommended ages of 11–12, 65.7% were vaccinated after their self-reported sexual debut, 3.8% had a lab-confirmed STI and 3.5% had vaccine-type HPV. There was no association between HPV vaccination and any STIs (adjusted odds ratio [aOR] 0.67, 95%CI:0.38–1.20), and vaccinated participants had 61% reduced odds of vaccine-type HPV (vs. unvaccinated; aOR 0.39, 95%CI:0.19–0.83). Results from the PS sensitivity analysis were similar to the main findings.ConclusionAmong females who reported a history of sexual activity, HPV vaccination status was protective against vaccine-type HPV and not associated with lab-based STI outcomes. Although findings may be susceptible to reporting bias, results indicating low vaccine uptake at routine-recommended ages requires additional efforts promoting HPV vaccination before sexual-debut.     

"Cutting" on cancer: attitudes about cancer spread and surgery among primary care patients in the U.S.A

Many underserved groups in the United States experience disparities in cancer survival. Part of the disparity may be due to differences in treatment or treatment uptake. Previous studies uncovered patient beliefs that surgery could cause cancer to spread and have suggested that this belief may affect uptake of cancer treatment. We explored patients’ explanations about surgical treatment of cancer and cancer spread, as well as the perceived impact on decision-making among primary care patients from an underserved area. Focus groups and interviews were conducted with patients (n = 42) at a primary care federally qualified health center in 2006 and 2007. Focus groups/interviews were semi-structured and were audio-taped and transcribed. An inductive text analysis with multiple coders was used to analyze the data and extract themes. We found that nearly all respondents had heard that surgery (“cutting”) and exposing cancer to the air would hasten cancer spread and result in worse outcomes. Most participants expressed agreement with this belief. Many participants said this concern would influence their decision about whether to have surgery and/or reported that a family member had refused surgery for this reason. A smaller group of respondents disagreed with this belief and offered experiential evidence to the contrary or hypotheses about its origination. The idea that “cutting” and “air” during surgery can cause cancer to spread may be more prevalent among patients than suspected, based on this sample of predominantly African American patients. While we were unable to disentangle the ideas about “cutting” from those about “exposure to air”, this set of beliefs, when held strongly, can negatively influence patients’ or family members’ decisions to seek surgical care and, if it is more prevalent in underserved groups, may contribute to cancer disparities.     

Urinary phthalate metabolites and metabolic syndrome in U.S. adolescents: Cross-sectional results from the National Health and Nutrition Examination Survey (2003–2014) data

Objective

There is limited research on the association between phthalates and metabolic syndrome (MetS). Among adolescents, phthalate exposure, which can occur from multiple sources, has been linked to several risk factors for MetS. The objective was to investigate the association between urinary phthalate metabolite concentrations (i.e., mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), mono-(3-carboxylpropyl) phthalate (MCPP), and di(2-ethylhexyl phthalate (DEHP)) and MetS in adolescents aged 12–19 years using the National Health and Nutrition Examination Survey (NHANES) data (2003–2014). A secondary aim was to assess if observed associations varied by a measure of socioeconomic status, economic adversity, which was defined using parental income and educational attainment as well as household food security.

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9–45 years of age: A phase 3 open-label study

BackgroundThe 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16–26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9–19 years and 27–45 years with Chinese females aged 20–26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9–19 years.MethodsParticipants aged 9–45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded.ResultsIn total, 1990 participants (690 aged 9–19 years; 650 aged 20–26 years; 650 aged 27–45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9–19-year age group were non-inferior to those in participants aged 20–26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27–45-year age group were non-inferior to those in participants aged 20–26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9–19, 20–26, and 27–45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths.ConclusionAntibody responses induced by 9vHPV vaccination in Chinese females aged 9–19 years and 27–45 years were non-inferior to those in Chinese females aged 20–26 years. The vaccine was generally well tolerated.ClinicalTrials.gov Identifier: NCT03903562.     

Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years: A phase 3, open-label,immunobridging study

BackgroundThe quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was approved for use in Chinese women aged 20–45 years in 2017. This Phase 3, open-label study (NCT03493542) aimed to assess immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9–19 years versus Chinese young women aged 20–26 years; we report results from Day 1 through Month 7. The study will continue through Month 60 to assess antibody persistence in Chinese girls aged 9–19 years.MethodsParticipants aged 9–26 years received three doses of the qHPV vaccine (Day 1, Month 2, Month 6). Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay (cLIA) in serum samples obtained on Day 1 and at Month 7. Injection-site adverse events (AEs) and systemic AEs within 30 days post-vaccination, and serious AEs (SAEs) occurring at any time during the study, were recorded.ResultsIn total, 766 participants (383 aged 9–19 years; 383 aged 20–26 years) were enrolled and received ≥1 vaccine dose. All participants in the per-protocol immunogenicity population of both age groups seroconverted to each of the vaccine HPV types at Month 7. Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9–19 years were non-inferior to those in participants aged 20–26 years. Injection-site AEs and systemic AEs were reported by 36.6% and 49.3% of 9–19-year-olds, and 40.7% and 54.8% of 20–26-year-olds, respectively. There were no vaccine-related SAEs. No participants discontinued the vaccine due to an AE and no deaths were reported.ConclusionAntibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9–19 years were non-inferior to those in Chinese young women aged 20–26 years. The vaccine was generally well tolerated in the study population.ClinicalTrials.gov Identifier: NCT03493542.     

High seroprevalence of multiple high-risk human papillomavirus types among the general population of Bonaire,St. Eustatius and Saba,Caribbean Netherlands

BackgroundIncidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017.MethodsBlood samples from participants (n = 1,823, 0–90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged ≥ 15 years who ever had sex (n = 1,080).ResultsAmong unvaccinated individuals aged ≥ 15 years, overall seropositivity was high (34%), with over half of them being seropositive for ≥ 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20–59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity.ConclusionsIn accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program.     

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27–45 years of age compared to women 16–26 years of age: An open-label phase 3 study

BackgroundEfficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16–26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27–45 versus 16–26 years of age.MethodsThis international, open-label study (NCT03158220) was conducted in women 16–45 years of age. Participants (16–26 years, n = 570 and 27–45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study.ResultsAt month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27–45 years were compared to those in women 16–26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27–45 years to 16–26 years) was 0.60–0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27–45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16–26 years, and 85.2% and 24.1% of women 27–45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study.ConclusionsThe 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27–45 years compared with women 16–26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16–26 years to women 27–45 years of age.Clinical trial registration NCT03158220.