Real-world impact and effectiveness assessment of the quadrivalent HPV vaccine: a systematic review of study designs and data sources.

INTRODUCTION: Vaccine effectiveness and impact studies are typically observational, generating evidence after vaccine launch in a real-world setting. For human papillomavirus (HPV) vaccination studies, the variety of data sources and methods used is pronounced. Careful selection of study design, data capture and analytical methods can mitigate potential bias in such studies. AREAS COVERED: We systematically reviewed the different study designs, methods, and data sources in published evidence (1/2007-3/2020), which assessed the quadrivalent HPV vaccine effectiveness and impact on cervical/cervicovaginal, anal, and oral HPV infections, anogenital warts, lesions in anus, cervix, oropharynx, penis, vagina or vulva, and recurrent respiratory papillomatosis. EXPERT OPINION: The rapid growth in access to real-world data allows global monitoring of effects of different public health interventions, including HPV vaccination programs. But the use of data which are not collected or organized to support research also underscore a need to develop robust methodology that provides insight of vaccine effects and consequences of different health policy decisions. To achieve the WHO elimination goal, we foresee a growing need to evaluate HPV vaccination programs globally. A critical appraisal summary of methodology used will provide timely guidance to researchers who want to initiate research activities in various settings.

Point-of-care testing and treatment of sexually transmitted and genital infections during pregnancy in Papua New Guinea (WANTAIM trial): protocol for an economic evaluation alongside a cluster-randomised trial.

INTRODUCTION: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG. METHODS AND ANALYSIS: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017-2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs. ETHICS AND DISSEMINATION: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs. TRIAL REGISTRATION NUMBER: ISRCTN37134032.

Human Papillomavirus Vaccination After COVID-19.

The current global novel coronavirus disease 2019 (COVID-19) pandemic threatens to derail the uptake of human papillomavirus (HPV) vaccination in low- and lower-middle income countries with major disruptions to routine immunization and the introduction of new vaccines delayed. This has a major impact on the World Health Organization cervical cancer elimination strategy, where it is dependent on HPV vaccination as well as cervical cancer screening and treatment. We discuss current opportunities and barriers to achieve high uptake of HPV vaccination in low- and lower-middle income countries as well as the impact of COVID-19. Implementation of 4 key recommendations for HPV vaccination in low- and lower-middle income countries is needed: increased global financial investment; improved vaccine supply and accelerated use of a single-dose schedule; education and social marketing; and adoption of universal school-based delivery. With the commitment of the global health community, the adoption of these strategies would underpin the effective elimination of cervical cancer.

Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population.

Routine cervical screening by primary HPV testing: early findings in the renewed National Cervical Screening Program.

OBJECTIVES: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV-positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology- to primary HPV-based screening. DESIGN, PARTICIPANTS: Retrospective cross-sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 - 31 May 2018. SETTING: Large community-based general pathology laboratory in metropolitan Sydney. MAIN OUTCOME MEASURES: Prevalence of oncogenic HPV types (all, HPV16/18, non-HPV16/18) by reason for HPV test (primary screening, non-screening); for oncogenic HPV-positive women in the age band recommended for primary HPV screening (25-74 years), prevalence of cytologic abnormality and rates of 12-month follow-up and colposcopy recommendations. RESULTS: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non-screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9-8.2%) and 20.9% of non-screening tests (95% CI, 20.5-21.3%); 35.5% (95% CI, 34.7-36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18-positive samples with high grade abnormality was 15.3% (95% CI, 14.2-16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8-6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3-5.5%) and direct colposcopy for 2.6% (95% CI, 2.5-2.7%) of screened women aged 25-74 years. CONCLUSIONS: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology-based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non-screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round.

Cross-sectional study estimating the psychosocial impact of genital warts and other anogenital diseases in South Korea.

OBJECTIVES: To estimate self-reported human papillomavirus (HPV) disease-related psychosocial impact among male and female patients in South Korea. DESIGN: In this multicentre cross-sectional study, psychosocial impacts were estimated using a one-time survey capturing HPV Impact Profile (HIP) results, CuestionarioEspecifico en Condilomas Acuminados (CECA; in Spanish)-'Specific questionnaire for Condylomata Acuminata' and the EuroQol-5 Dimension (EQ-5D) surveys. Student's t-tests or Mann-Whitney U tests were used for continuous comparisons; χ2 or Fisher's exact tests were applied for categorical comparisons. SETTING: 5098 clinics throughout Seoul, Busan, Daegu, Kwangju and Daejeon (South Korea). PARTICIPANTS: Patients with and without genital warts (GW) (males) and selected HPV diseases (females) visiting primary care physicians, obstetricians/gynaecologists, urologists and dermatologists with 2-30 years experience. RESULTS: Of 150 male and 250 female patients, HIP scores showed 85.3% of male patients with GW and 32.0% without reported moderate psychological impact (p<0.0001). In categorised total scores, 88.5% of female patients with and 66.0% without selected HPV-related diseases reported moderate or high psychological impacts (p=0.0004). In the CECA questionnaire, male patients had mean (SD) scores of 10.51 (3.79) in 'emotional health' and 15.90 (6.13) in 'sexual activity'. Female patients with GW reported lower scores in both dimensions with mean scores of 7.18 (4.17) in 'emotional health' and 10.97 (5.80) in 'sexual activity' (p<0.0001), indicating worse health-related quality of life (HRQoL). For the EQ-5D, male patients with GW reported lower mean Visual Analogue Scale (VAS) scores than those without (75.1 vs 81.13, p<0.0135). Mean VAS score and utility values were lower for females with HPV-related diseases than those without (72.18 vs 76.86 and 0.90 vs 0.94, respectively). CONCLUSION: In South Korea, GW in men and HPV-related diseases in women negatively impact patient well-being and HRQoL scores. Among women, those with GW suffered a greater psychosocial impact than those with other selected HPV-related diseases.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PURPOSE: To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. METHODS: The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. RESULTS: Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. RECOMMENDATIONS: In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended.It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

A cross-sectional study estimating the burden of illness related to genital warts in South Korea.

OBJECTIVES: Estimate the prevalence of genital warts (GW) and GW-related healthcare resource use and costs among male and female patients seeking treatment in South Korea. DESIGN: To estimate GW prevalence, physicians in five major South Korean regions recorded daily logs of patients (n=71 655) seeking care between July 26 and September 27, 2011. Overall prevalence estimates (and 95% CIs) were weighted by the estimated number of physicians in each specialty and the estimated proportion of total patients visiting each specialist type. Healthcare resource use was compared among different specialties. Corresponding p values were calculated using Mann-Whitney U tests. SETTING: The database covers 5098 clinics and hospitals for five major regions in South Korea: Seoul, Busan, Daegu, Gwangju and Daejeon. PARTICIPANTS: Primary care physicians (general practice/family medicine), obstetricians/gynaecologists, urologists and dermatologists with 2-30 years' experience. RESULTS: The estimated overall GW prevalence was 0.7% (95% CI 0.7% to 0.8%). Among women, GW prevalence was 0.6% (95% CI 0.6% to 0.7%); among men prevalence was 1.0% (95% CI 0.9% to 1.0%), peaking among patients aged 18-24 years. Median costs for GW diagnosis and treatment for male patients were US$58.2 (South Korean Won (KRW) ₩66 857) and US$66.3 (KRW₩76 113) for female patients. CONCLUSIONS: The estimated overall GW prevalence in South Korea was 0.7% and was higher for male patients. The overall median costs associated with a GW episode were higher for female patients than for male patients.

Prevalence and severity of dysmenorrhoea, and management options reported by young Australian women.

BACKGROUND: Little is known about the severity of dysmenorrhoea and attitudes towards its management in young females. OBJECTIVE: The aim of this study was to evaluate the prevalence and severity of dysmenorrhoea in women aged 16-25 years. METHODS: Participants were recruited via targeted Facebook advertising and asked to complete an online questionnaire covering medications, menstruation and lifestyle-related themes. A follow-up questionnaire on dysmenorrhoea was also administered. RESULTS: The prevalence of dysmenorrhoea was 88% (n = 247, mean age 21.5 years, SD 2.6). Only 34% of participants reported consulting a healthcare provider about their pain, whereas 86% consulted other sources. Pain medication was used by 58% of the participants. Dysmenorrhoea was associated with interference with daily activities (P DISCUSSION: Dysmenorrhoea is highly prevalent among these women, with most indicating moderate to severe pain and a significant adverse impact on daily activities. Most women did not obtain information about dysmenorrhoea from healthcare providers, indicating the need for general practitioners to provide accurate information about dysmenorrhoea to young females.

Estimation of Cancer Burden Attributable to Infection in Asia.

BACKGROUND: Some infectious agents have been shown to be human carcinogens. The current study focused on estimation of cancer burden attributable to infection in different regions of Asia. METHODS: By systematically reviewing previous studies of the infection prevalence data of 13 countries in Asia and relative risks of specific cancers, we calculated the population attributable fraction of carcinogenic infections. Using data from GLOBOCAN 2012, the overall country-specific and gender-specific number of new cancer cases and deaths resulting from infection were estimated. RESULTS: Across 13 principal Asian countries, the average prevalence and range was 6.6% (0.5% in Japanese women to 15.0% in Vietnamese men) for hepatitis B virus (HBV), 2.6% (0.3% in Iran to 5.1% in Saudi Arabia) for hepatitis C virus (HCV), 7.9% (2.8% in Pakistan to 17.7% in China) for human papillomavirus (HPV), and 61.8% (12.8% in Indonesia to 91.7% in Bangladesh) for Helicobacter pylori (HP). The estimated total number of cancer cases and deaths caused by infection in these 13 countries were 1 212 026 (19.6% of all new cancer cases) and 908 549 (22.0% of all deaths from cancer). The fractions of cancer incidence attributable to infection were 19.7% and 19.5% in men and women, respectively. The percentages of cancer deaths attributable to infection were 21.9% and 22.1% in men and women, respectively. Among the main infectious agents, HP was responsible for 31.5% of infection-related cancer cases and 32.8% of infection-related cancer deaths, followed by HBV (28.6% of new cases and 23.8% of deaths), HPV (22.0% of new cases and 27.3% of deaths), and HCV (12.2% of new cases and 10.6% of deaths). CONCLUSIONS: Approximately one quarter of all cancer cases and deaths were infection-associated in Asia, which could be effectively prevented if appropriate long-term controls of infectious agents were applied.

Reduced dose human papillomavirus vaccination: an update of the current state-of-the-art.

Human papillomavirus (HPV) infection is the primary cause of genital warts, some oropharyngeal cancers and anogenital cancers, including cervical, vagina, vulvar, anal and penile cancers. Primary prevention of cervical cancer requires the prevention of high-risk HPV infections, particularly HPV genotypes 16 and 18. Both Gardasil® and Cervarix® vaccines when administered by a three-dose schedule have been demonstrated to be effective against cervical, vulva, and vaginal cancer precursors from vaccine genotypes in phase III clinical trials, and post-marketing studies; Gardasil® vaccine also offers additional protection against anal cancer precursors. However, high costs of HPV vaccines and the logistics of delivering a three-dose schedule over 6 months are challenging in countries with limited resources. Several studies have demonstrated non-inferiority in antibody response between adolescents (9-15 years old) who received two doses (6 months apart) and women (>15 years old) who received the standard three-dose schedule. These studies provided evidence for the World Health Organization and European Medical Association to revise its recommendation to give two instead of three doses of HPV vaccine to adolescents below 15 years of age, provided the 2nd dose is given 6 months apart. Although reduced dose schedules can alleviate costs and logistics associated with HPV vaccination, especially in resource-poor countries, there are still gaps in this area of research, particularly regarding long-term protection. This review discusses the findings on antibody response and clinical outcomes in studies evaluating reduced dose HPV schedules, and highlights the important considerations of its implementation. In addition, other important immunological biomarkers that may be associated with long-term protection are highlighted and discussed.

In vitro assessment of the effect of vaccine-targeted human papillomavirus (HPV) depletion on detection of non-vaccine HPV types: implications for post-vaccine surveillance studies.

In populations where the prevalence of vaccine-targeted HPV types has been reduced significantly due to widespread vaccination of the target population, the sensitivity of some consensus PCR-based assays to detect remaining HPV types may be altered, leading to misrepresentations of prevalence. Importantly, this may lead to false indications of type replacement in vaccinated populations. To assess whether excess vaccine-targeted HPV DNA resulted in reduced detection of other genotypes on the Roche HPV linear array genotype assay, simulated samples containing 1000 copies of one or two high-risk HPV DNA genomes in the presence and the absence of 10,000 copies of the HPV16 genome were tested. HPV16 alone did not affect detection of other high-risk genotypes; however when HPV16 and an additional genotype were present, detection of HPV31, 33, 51 or 59 was impeded, indicating potential for misrepresentation of population-based prevalence of these genotypes and false evidence for type replacement following vaccination.

Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study.

BACKGROUND: After the introduction of a quadrivalent human papillomavirus (HPV) vaccination programme in Australia in April, 2007, we measured the prevalence of vaccine-targeted and closely related HPV types with the aim of assessing direct protection, cross-protection, and herd immunity. METHODS: In this repeat cross-sectional study, we recruited women aged 18-24 years who attended Pap screening between October, 2005, and July, 2007, in three major metropolitan areas of Australia to form our prevaccine-implementation sample. For our postvaccine-implementation sample, we recruited women aged 18-24 years who attended Pap screening in the same three metropolitan areas from August, 2010, to November, 2012. We compared the crude prevalence of HPV genotypes in cervical specimens between the prevaccine and the postvaccine implementation groups, with vaccination status validated against the National HPV Vaccination Program Register. We estimated adjusted prevalence ratios using log linear regression. We estimated vaccine effectiveness both for vaccine-targeted HPV types (16, 18, 6, and 11) and non-vaccine but related HPV types (31, 33, and 45). FINDINGS: 202 women were recruited into the prevaccine-implementation group, and 1058 were recruited into the postvaccine-implementation group. Crude prevalence of vaccine-targeted HPV genotypes was significantly lower in the postvaccine-implementation sample than in the prevaccine-implementation sample (58 [29%] of 202 vs 69 [7%] of 1058; p<0·0001). Compared with the prevaccine-implementation sample, adjusted prevalence ratios for vaccine-targeted HPV genotypes were 0·07 (95% CI 0·04-0·14; p<0·0001) in fully vaccinated women and 0·65 (0·43-0·96; p=0·03) in unvaccinated women, which suggests herd immunity. No significant declines were noted for non-vaccine-targeted HPV genotypes. However, within the postvaccine-implementation sample, adjusted vaccine effectiveness against vaccine-targeted HPV types for fully vaccinated women compared with unvaccinated women was 86% (95% CI 71-93), and was 58% (26-76) against non-vaccine-targeted but related genotypes (HPV 31, 33, and 45). INTERPRETATION: 6 years after the initiation of the Australian HPV vaccination programme, we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women, suggesting herd immunity; and a possible indication of cross-protection against HPV types related to the vaccine-targeted types in vaccinated women. FUNDING: Australian National Health and Medical Research Council and Cancer Council Victoria.

Rationale and design of REACT: a randomised controlled trial assessing the effectiveness of home-collection to increase chlamydia retesting and detect repeat positive tests.

BACKGROUND: Repeat infection with Chlamydia trachomatis is common and increases the risk of sequelae in women and HIV seroconversion in men who have sex with men (MSM). Despite guidelines recommending chlamydia retesting three months after treatment, retesting rates are low. We are conducting the first randomised controlled trial to assess the effectiveness of home collection combined with short message service (SMS) reminders on chlamydia retesting and reinfection rates in three risk groups. METHODS/DESIGN: The REACT (retest after Chlamydia trachomatis) trial involves 600 patients diagnosed with chlamydia: 200 MSM, 200 women and 200 heterosexual men recruited from two Australian sexual health clinics where SMS reminders for retesting are routine practice. Participants will be randomised to the home group (3-month SMS reminder and home-collection) or the clinic group (3-month SMS reminder to return to the clinic). Participants in the home group will be given the choice of attending the clinic if they prefer. The mailed home-collection kit includes a self-collected vaginal swab (women), UriSWAB (Copan) for urine collection (heterosexual men), and UriSWAB plus rectal swab (MSM). The primary outcome is the retest rate at 1-4 months after a chlamydia diagnosis, and the secondary outcomes are: the repeat positive test rate; the reinfection rate; the acceptability of home testing with SMS reminders; and the cost effectiveness of home testing. Sexual behaviour data collected via an online survey at 4-5 months, and genotyping of repeat infections, will be used to discriminate reinfections from treatment failures. The trial will be conducted over two years. An intention to treat analysis will be conducted. DISCUSSION: This study will provide evidence about the effectiveness of home-collection combined with SMS reminders on chlamydia retesting, repeat infection and reinfection rates in three risk groups. The trial will determine client acceptability and cost effectiveness of this strategy. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12611000968976.

Sexual behaviors and risk for sexually transmitted infections among teenage men who have sex with men.

OBJECTIVES: To report on sexual behaviors and sexually transmitted infections (STIs) among men who have sex with men (MSM) in their teens, when many MSM engage in their first sexual experiences. METHODS: MSM aged 16 to 20 years were recruited via community and other sources. Men completed a questionnaire about their sexual behaviors and were screened for gonorrhea, chlamydia, syphilis, and HIV. RESULTS: Two hundred men were included. The median age was 19 years. The median age at first insertive or receptive anal intercourse was 17 years. Half of men reported sex with mainly older men: these men were more likely to engage in receptive anal intercourse (48% vs. 25%, p < .001) than other men. Most men had engaged in insertive (87%) and receptive (85%) anal intercourse in the prior 12 months with 60% and 53% reporting inconsistent condom use with insertive and receptive anal intercourse partners, respectively. The median number of insertive anal intercourse partners was 3 and 1.5 (p < .001) among men reporting inconsistent and consistent condom use with insertive anal intercourse over the prior 12 months. The median number of receptive anal intercourse partners was 3 and 2 (p = .006) among men reporting inconsistent and consistent condom use with receptive anal intercourse over the prior 12 months. Pharyngeal gonorrhea, rectal gonorrhea, urethral chlamydia, rectal chlamydia, and syphilis were detected in 3.0%, 5.5%, 3.0%, 4%, and 2.0% of men, respectively. All men were HIV negative. CONCLUSION: Many of the teenage MSM in this study were at risk for STI. Preventative messages and STI screening interventions that are age appropriate need to be developed to reduce HIV and STI risk in this under-recognized group.

The Australian experience with the human papillomavirus vaccine.

OBJECTIVE: The goal of this study was to review the current human papillomavirus (HPV) vaccine program and its outcomes to date in Australia. METHODS: This was a review of the published data relating to the introduction and subsequent measurable outcomes of the quadrivalent vaccine, which became part of the Australian national HPV immunization program in 2007. Australia commenced an ongoing, schoolbased, government-funded, HPV vaccination program using the quadrivalent vaccine from April 2007 for adolescent female subjects aged 12 to 13 years, together with a catch-up program for female subjects 13 to 26 years of age from July 2007 to December 31, 2009. RESULTS: The Australian community (lay and clinical) have embraced the program, resulting in high coverage with >70% for 3 doses in the 12- to 13-year-old ongoing target population. Vaccine effectiveness (outcomes of vaccination in a real-world setting) is already being seen. This effectiveness has been noted in significant reductions in HPV vaccine-related infections in vaccine eligible age female subjects (77% fall in prevalence), rapid reduction of >90% in genital warts (first marker of disease reduction, as well as herd immunity), and reduction in high-grade cervical lesions in this age group. These remarkable changes so soon after implementation of the vaccine in the country occurred faster, and to a greater extent, than anyone could have predicted. CONCLUSIONS: These findings from Australia should encourage other countries to follow suit, with the ultimate aim of translating treatment into reductions in HPV-related neoplasia globally. The greatest success from such an approach will only be realized when prophylactic vaccines are rolled out effectively, with high coverage and at affordable costs, to those areas of the world with the highest burden of disease. To achieve this outcome requires government endorsement and commitment; education of the community at large; realization of the safety, efficacy, and immunogenicity of the available prophylactic vaccines in reducing HPV-related infections and disease, especially neoplasia; and governments procuring vaccines at affordable prices through the various options now available (eg, support from the GAVI Alliance to eligible countries, tiered pricing, negotiation with pharmaceutical manufacturers). We have the tools to reach this goal, and it is time these tools were implemented.

Cervical cancer burden and prevention strategies: Asia Oceania perspective.

The Asia Oceania region contributes to more than 50% of cervical cancer cases worldwide. Yet cervical cancer is one of few cancers that can be prevented through comprehensive screening for precancerous lesions, with their subsequent treatment. Screening with cervical cytology, a very old technology, has reduced cervical cancer mortality and incidence when applied in comprehensive programs with high coverage and high quality assurance. However, of those countries within this region that have set up such programs, many have been opportunistic, had poor coverage, or inadequate treatment facilities for lesions found. Consequently, they have not seen large reductions in cancer incidence or mortality. Some have therefore adopted visual inspection by acetic acid (VIA) and Lugol's iodine (VILI) or human papillomavirus (HPV) DNA assays for screening. With two safe, immunogenic and efficacious prophylactic vaccines licensed, the way forward to reduction of cervical cancer to becoming uncommon is within reach. Where governments have supported high coverage public-health vaccination programs, reductions in disease burden with shortest incubation (genital warts, high-grade abnormalities) are already being reported. One of the biggest impediments is the cost of vaccines that are affordable to resource-poor countries. Other challenges include, infrastructure for delivery of vaccines, plus general acceptance of vaccination by the community.

Assessment of first sexual intercourse in young women with a history of childhood sexual abuse.

Women reporting childhood sexual abuse (CSA) that involved actual or attempted penetration may not identify this as their first sexual intercourse. Data were drawn from a population-based, prospective cohort study spanning adolescence to adulthood. CSA prior to age 16 and age of first sexual intercourse with a male were assessed retrospectively. More than half of women reporting CSA in the form of actual or penetrative abuse reported an age of first sexual intercourse at or beyond 16 years. Direct questioning about CSA is needed to accurately ascertain sexual history.