Human papillomavirus vaccine effectiveness by number of doses: Systematic review of data from national immunization programs.

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

Genotype-specific Concordance of Chlamydia trachomatis Genital Infection within Heterosexual Partnerships

Background Sexual transmission rates of Chlamydia trachomatis (Ct) cannot be measured directly; however, the study of concordance of Ct infection in sexual partnerships (dyads) can help to illuminate factors influencing Ct transmission. Methods Heterosexual men and women with Ct infection and their sex partners were enrolled and partner-specific coital and behavioral data collected for the prior 30 days. Microbiological data included Ct culture, nucleic acid amplification testing (NAAT), quantitative Ct polymerase chain reaction (qPCR), and ompA genotyping. We measured Ct concordance in dyads, and factors (correlates) associated with concordance. Results 121 women and 125 men formed 128 dyads. Overall, 72.9% of male partners of NAAT-positive women and 68.6% of female partners of NAAT-positive men were Ct-infected. Concordance was more common in dyads with culture-positive members (78.6% of male partners, 77% of female partners). Partners of women and men who were NAAT-positive only had lower concordance (33.3%, 46.4%, respectively). Women in concordant dyads had significantly higher median endocervical qPCR values (3,032) compared with CT-infected women in discordant dyads (1,013 IFU DNA equivalents per ml), p<0.01. Among 54 Ct-concordant dyads with ompA genotype data for both members, 96.2% had identical genotypes. Conclusions Higher organism load appears associated with concordance among women. Same-genotype chlamydial concordance was high in sexual partnerships. No behavioral factors were sufficiently discriminating to guide partner services activities. Findings may help model coitus-specific transmission probabilities

HPV Genotypes in High Grade Cervical Lesions and Invasive Cervical Carcinoma as Detected by Two Commercial DNA Assays, North Carolina, 2001–2006

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.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.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.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

Acceptability of school requirements for human papillomavirus vaccine

We characterized parental attitudes regarding school HPV vaccination requirements for adolescent girls. Study participants were 866 parents of 10–18 y-old girls in areas of North Carolina with elevated cervical cancer incidence. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression. Approximately half (47%) of parents agreed that laws requiring HPV immunization for school attendance “are a good idea” when opt-out provisions were not mentioned. Far more agreed that “these laws are okay only if parents can opt out if they want to” (84%). Predictors of supporting requirements included believing HPV vaccine is highly effective against cervical cancer (OR = 2.5, 95% CI:1.7–5.0) or is more beneficial if provided at an earlier age (OR = 16.1, 95% CI:8.4–31.0). Parents were less likely to agree with vaccine requirements being a good idea if they expressed concerns related to HPV vaccine safety (OR = 0.3, 95% CI:0.1–0.5), its recent introduction (OR = 0.3, 95% CI:0.2–0.6). Parental acceptance of school requirements appears to depend on perceived HPV vaccine safety and efficacy, understanding of the optimal age for vaccine administration, and inclusion of opt-out provisions

Human papillomavirus vaccine effectiveness by number of doses: Updated systematic review of data from national immunization programs.

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

Cost-effectiveness of Human Papillomavirus Vaccination in the United States

Results of a simplified model were consistent with published studies based on more complex models when key assumptions were similar

Comprehensive Control of Human Papillomavirus Infections and Related Diseases

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. (C) 2013 Elsevier Ltd. All rights reserved

Acceptability of Carraguard Vaginal Microbicide Gel among HIV-Infected Women in Chiang Rai, Thailand

Background: Few studies of microbicide acceptability among HIV-infected women have been done. We assessed CarraguardH vaginal gel acceptability among participants in a randomized, controlled, crossover safety trial in HIV-infected women in Thailand. Methodology/Principal Findings: Participants used each of 3 treatments (Carraguard gel, methylcellulose placebo gel, and no product) for 7 days, were randomized to one of six treatment sequences, and were blinded to the type of gel they received in the two gel-use periods. After both gel-use periods, acceptability was assessed by face-to-face interview. Responses were compared to those of women participating in two previous Carraguard safety studies at the same study site. Sixty women enrolled with a median age of 34 years; 25 % were sexually active. Self-reported adherence (98%) and overall satisfaction rating of the gels (87% liked ‘‘somewhat’ ’ or ‘‘very much’’) were high, and most (77%) considered the volume of gel ‘‘just right.’ ’ For most characteristics, crossover trial participants evaluated the gels more favorably than women in the other two trials, but there were few differences in the desired characteristics of a hypothetical microbicide. Almost half (48%) of crossover trial participants noticed a difference between Carraguard and placebo gels; 33 % preferred Carraguard while 12 % preferred placebo (p=0.01). Conclusions/Significance: Daily Carraguard vaginal gel use was highly acceptable in this population of HIV-infecte

Review of the current published evidence on single-dose HPV vaccination 3rd Edition

Prophylactic human papillomavirus (HPV) vaccines have been licensed for over ten years. They were initially administered as a three-dose regimen over a six-month period. In 2014, following a review of the evidence for dose reduction by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization, a two-dose regimen for individuals aged younger than 15 years was recommended. Since that time, evidence from observational studies suggests that a single-dose HPV vaccine may also provide protection against HPVinfectionand its sequelae. The primary objective of this paperis to summarize and assess the current evidence fora single-dose HPV vaccination schedule. We also identify gaps that remain in determining whether a single dose could be sufficiently protective to have a major impact against HPV infection and its sequelae within the context of immunization programs.The evidence has been compiled by a working group of the Single-Dose HPV Vaccine Evaluation Consortium, whose members representtechnical depth, a wide global reach, and extensive expertise in immunization programs, HPV vaccine introductions, and vaccine policy. Coordinated by PATH, the Consortium includes the London School of Hygiene & Tropical Medicine, the US Centers for Disease Control and Prevention, Harvard University, the US National Cancer Institute, Université Laval, the University of British Columbia, and the Wits Reproductive Health and HIV Institute at the University of Witwatersrand. The Consortium leverages the experience of expert groups working in HPV vaccine and other vaccine introductions. Members represent groups that have actively generated evidence for HPV vaccine safety and efficacy,as well as post-licensure effectiveness and delivery.They have implemented HPV vaccine delivery programs in numerous countries, comprehensively evaluated the delivery and impact of HPV vaccine