Jessica A. Kahn

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

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

Vaccine-Type Human Papillomavirus and Evidence of Herd Protection After Vaccine Introduction

OBJECTIVES: The aims of this study were to compare prevalence rates of human papillomavirus (HPV) in young women before and after HPV vaccine introduction to determine the following: (1) whether vaccine-type HPV infection decreased, (2) whether there was evidence of herd protection, and (3) whether there was evidence for type-replacement (increased prevalence of nonvaccine-type HPV). METHODS: Young women 13 to 26 years of age who had had sexual contact were recruited from 2 primary care clinics in 2006–2007 for a prevaccination surveillance study (N = 368, none were vaccinated) and 2009–2010 for a postvaccination surveillance study (N = 409, 59% were vaccinated). Participants completed a questionnaire and were tested for cervicovaginal HPV DNA. HPV prevalence rates were compared in the pre- versus postsurveillance studies by using χ2 tests. Propensity score weighting was used to balance differences in covariates between the 2 surveillance studies. RESULTS: The mean age was ∼19 years for both groups of participants and most were African American and non-Hispanic. After propensity score weighting, the prevalence rate for vaccine-type HPV decreased substantially (31.7%–13.4%, P < .0001). The decrease in vaccine-type HPV not only occurred among vaccinated (31.8%–9.9%, P < .0001) but also among unvaccinated (30.2%–15.4%, P < .0001) postsurveillance study participants. Nonvaccine-type HPV increased (60.7%–75.9%, P < .0001) for vaccinated postsurveillance study participants. CONCLUSIONS: Four years after licensing of the quadrivalent HPV vaccine, there was a substantial decrease in vaccine-type HPV prevalence and evidence of herd protection in this community. The increase in nonvaccine-type HPV in vaccinated participants should be interpreted with caution but warrants further study.

Integrating Clinical, Community, and Policy Perspectives on Human Papillomavirus Vaccination

Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This review summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated framework can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.

Mycoplasma genitalium detected by transcription-mediated amplification is associated with Chlamydia trachomatis in adolescent women.

Objectives: The clinical significance of Mycoplasma genitalium (MG) infection in adolescent women is poorly understood. We compared the prevalence of MG with that of other sexually transmitted organisms such as Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) and assessed the associations of MG with sexual behaviors, genitourinary symptoms, physical and laboratory findings. Study Design: Women aged 14 to 21 years (n = 331) were recruited from an urban medical center. The subjects’ sexual behaviors, genitourinary symptoms, and physical findings were recorded. Endocervical swabs were collected for CT and NG testing and vaginal swabs for wet mount, Gram stain, TV and MG testing. MG infection was identified by nucleic acid amplification using a transcription-mediated amplification assay. Results: MG was detected in 74 (22.4%), CT in 79 (24.4%), TV in 60 (18.2%), and NG in 35 (10.7%) subjects. MG infection was not associated with vaginal symptoms, physical evidence of cervicitis, or findings on wet mount or Gram stain. In logistic regression, variables positively associated with MG were current CT [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.4–4.4] and recent sexual contact (≤7 days) (OR, 2.0; CI, 1.1–3.2). Dysuria (OR, 0.44; CI, 0.2–0.96) and use of hormonal contraception (OR, 0.55; CI, 0.3–1.0) were negatively associated with MG infection. Conclusion: In adolescent women, MG infection was as common as chlamydial infection and trichomoniasis and more common than gonorrhea. MG was associated with CT and recent sexual contact but not with vaginal symptoms or signs of cervicitis.

Adolescent Preferences for Human Immunodeficiency Virus Testing Methods and Impact of Rapid Tests on Receipt of Results

PURPOSE Rapid human immunodeficiency virus (HIV) tests may be more acceptable to adolescents and may improve receipt of test results. We conducted a study to determine (a) adolescent preferences for different HIV testing methods (rapid oral fluid vs. rapid fingerstick vs. traditional venipuncture), (b) factors associated with choice of a rapid vs. traditional test, and (c) whether those who chose a rapid method were more likely to receive test results. METHODS Participants (N=99, 13-22 years old, both genders) were recruited from an urban hospital-based adolescent primary care clinic, agreed to HIV testing with their choice of method, and completed a questionnaire assessing demographic characteristics and attitudes about HIV testing. Logistic regression modeling was used to determine factors associated with choice of a rapid versus traditional test. RESULTS Half (50.5%) of participants chose rapid oral fluid testing, 30.3% traditional venipuncture testing, and 19.2% rapid fingerstick testing (p < .01). Factors independently associated with choice of a rapid versus traditional method included preference for an oral fluid versus blood test and perceived approval of HIV testing by ones healthcare provider. Participants who chose a rapid test were more likely to receive their test results within the follow-up period than participants who chose a traditional test (91.3% vs. 46.7%, p < .001). CONCLUSIONS In this study, 70% of adolescents preferred rapid to traditional HIV testing, and rapid testers were more likely to receive their results within the follow-up period. Offering rapid testing may lead to improved receipt of results among adolescents in urban primary care settings.

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes

After introduction of vaccination, some prevalences of nonvaccine types changed, without clear evidence for type replacement.

Adolescent Human Immunodeficiency Virus Care Providers’ Attitudes Toward the Use of Oral Pre-Exposure Prophylaxis in Youth

Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is currently indicated for use in adults in the United States and may soon be indicated for minor adolescents. However, implementation of PrEP use among minors may present unique barriers. We conducted 15 individual, semi-structured interviews among US clinicians caring for HIV-infected and at-risk youth. The theory-driven interview guide assessed demographics, perceived role of oral PrEP in HIV prevention among adolescents, perceived barriers to and facilitating factors for use of PrEP in adolescents, and clinician-reported likelihood of prescribing PrEP. Transcripts were analyzed using framework analysis. Overall, clinicians viewed PrEP as a time-limited intervention that is one part of a comprehensive approach to HIV prevention among adolescents. Perceived barriers to prescribing to minors included concerns about: confidentiality, legality of minors consenting to PrEP without parental involvement, ability of minors to understand the risks/benefits of PrEP, the possible impact of PrEP on bone accrual, off-label use of PrEP medication in minors, and the high costs associated with PrEP use. Clinician-reported facilitating factors for prescribing PrEP to youth included educating communities and other clinicians about PrEP, ensuring adequate financial resources and infrastructure for delivering PrEP, developing formal guidance on effective behavioral interventions that should be delivered with PrEP, and gaining personal experience with prescribing PrEP. Clinicians indicated greater comfort with prescribing PrEP to adults versus minors. For PrEP to become more widely available to youth at risk for HIV infection, barriers that are unique to PrEP use in minors must be addressed.

Adolescents' agreement to test for HIV when different testing methods are offered.

Offering rapid HIV testing improves rates of testing in adults, but little is known about whether offering adolescents a choice of testing methods increases rates of testing. The aims of the study were to determine rates of HIV testing in adolescents when different testing methods were offered and explore factors associated with agreement to be tested for HIV. Participants (n= 200, sexually experienced 13–22 year olds) were recruited from an urban adolescent clinic, completed a 99-item theory-based survey and were offered their choice of venipuncture, rapid fingerstick or rapid oral fluid HIV testing. Approximately half (49.5%) agreed to HIV testing. Male gender, parental completion of high school, intention to test for HIV if offered by clinician and higher perceived likelihood of current HIV infection were independently associated with agreement to test. Combining new strategies, such as opt-out testing, with routine testing may be needed to improve rates of adolescent HIV testing.

Behavioral, immunologic, and virologic correlates of oral human papillomavirus infection in HIV-infected youth

Background Little is known about the epidemiology or risk factors for oral human papillomavirus (HPV) in HIV-infected youth. The objectives of this study were to determine the prevalence and correlates of oral HPV infection and to explore the association between HPV vaccination and oral infection in HIV-infected youth. Methods Youth 12 to 24 years of age with behaviorally acquired HIV were recruited for this cross-sectional study. Procedures involved medical chart review, survey, and collection of an oral rinse sample. Univariable and multivariable logistic regression models were used to determine whether demographic, behavioral, immunologic, and virologic factors and history of vaccination were significantly associated with oral HPV infection. Results Mean age of the 272 participants was 21.5 years; 64% were non-Hispanic black and 20.2% were Hispanic; and 10.8% of men compared with 20.3% of women were fully vaccinated. Human papillomavirus prevalence was 19.7% in men and 18.6% in women (P = 1.0). Only men were positive for vaccine-type HPV: 5.6% were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, and 4.2% were positive for HPV-16 and/or HPV-18. Among men who were fully vaccinated, none were positive for HPV-6, HPV-11, HPV-16, and/or HPV-18, compared with 12 (6.3%) of men who were not fully vaccinated (P = 0.37). Two variables were marginally associated with oral HPV (P < 0.10): marijuana use in the previous 3 months and lower CD4+ T-cell count. Conclusions Prevalence rates of oral HPV were relatively high in this population of HIV-infected youth and were similar in male and female youth. No fully vaccinated men were infected with vaccine-type HPV.

Non-Vaccine-type human papillomavirus prevalence after Vaccine introduction: No evidence for type replacement but evidence for cross-protection

Background We examined non–vaccine-type human papillomavirus (HPV) prevalence in a community before and during the first 8 years after vaccine introduction, to assess for (1) type replacement with any non–vaccine-type HPV and (2) cross-protection with non–vaccine types genetically related to vaccine-type HPV. Methods Sexually experienced 13- to- 26-year-old women were recruited for 3 cross-sectional studies from 2006 to 2014 (N = 1180). Outcome variables were as follows: (1) prevalence of at least 1 of 32 anogenital non–vaccine-type HPVs and (2) prevalence of at least 1 HPV type genetically related to HPV-16 and HPV-18. We determined changes in proportions of non–vaccine-type HPV prevalence across the study waves using logistic regression with propensity score inverse probability weighting. Results Vaccine initiation rates increased from 0% to 71.3%. Logistic regression demonstrated that from 2006 to 2014, there was no increase in non–vaccine-type HPV among vaccinated women (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 0.73–1.42), but an increase among unvaccinated women (AOR, 1.88; 95% CI, 1.16–3.04). Conversely, there was a decrease in types genetically related to HPV-16 among vaccinated (AOR, 0.57; 95% CI, 0.38–0.88) but not unvaccinated women (AOR, 1.33; 95% CI, 0.81–2.17). Conclusions We did not find evidence of type replacement, but did find evidence of cross-protection against types genetically related to HPV-16. These findings have implications for cost-effectiveness analyses, which may impact vaccine-related policies, and provide information to assess the differential risk for cervical cancer in unvaccinated and vaccinated women, which may influence clinical screening recommendations. The findings also have implications for public health programs, such as health messaging for adolescents, parents, and clinicians about HPV vaccination.