Summary 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.
Summary Background Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal ...intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9–37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6–17·6), and clearance occurred in 14·6% (10·2–21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8–35·4) with incidences of 8·5% (6·9–10·4) and 15·4% (11·8–19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2–60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8–15·4). Incidence of HPV-16 was 11·8% (9·2–14·9) and 5·8% (1·9–13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7–29·3), with incidence of 3·3% (2·2–4·7) and 6·0% (4·2–8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0–11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding Australian Government Department of Health and Ageing.
Summary Background Australia introduced a national quadrivalent human papillomavirus (4vHPV) vaccination programme for girls and young women in April, 2007. The HPV genotypes targeted by the female ...vaccine could also affect the protection afforded to heterosexual men. We examined the prevalence of 4vHPV targeted vaccine genotypes and the nine-valent HPV (9vHPV)-targeted vaccines genotypes among sexually active, predominantly unvaccinated heterosexual men from 2004 to 2015. Methods We did a retrospective, observational study of urine and urethral swab specimens from heterosexual men aged 25 years or younger attending the Melbourne Sexual Health Centre between July 1, 2004, and June 30, 2015, who tested positive for Chlamydia trachomatis . We extracted HPV DNA and used the PapType HPV assay to detect 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and two low-risk genotypes (6 and 11). We calculated the prevalence of any HPV genotype, genotypes 6 or 11, genotypes 16 or 18, genotypes in the 4vHPV group (6, 11, 16, or 18), five additional genotypes in the 9vHPV group (31, 33, 45, 52, or 58), and non-vaccine-targeted genotypes (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, or 68). Findings We obtained data between July 1, 2004, and June 30, 2015, and did the data analysis in December, 2015. Of 1764 specimens obtained, we included 1466 in our final analysis (the others were excluded because they had indeterminate results or were duplicates). The prevalence of any HPV genotype and genotypes 31, 33, 45, 52, and 58 did not change from 2004–05 to 2014–15, but we noted reductions in genotypes 6 and 11 (from 12% 95% CI 6–21%, to 3% 1–7%, ptrend =0·008), 16 and 18 (from 13% 95% CI 7–22% to 3% 1–6%, ptrend <0·0001), and 4vHPV-targeted genotypes (from 22% 95% CI 14–33% to 6% 3–10%, ptrend <0·0001). Prevalence of non-vaccine-targeted genotypes increased from 16% 95% CI 9–26% to 22% 17–29%, ptrend <0·0001). In Australian-born men, 4vHPV-targeted genotype prevalence decreased from 11 of 55 20%, 95% CI 10–33% to two of 74 3%, 0–11%, ptrend <0·0001); an even greater decline occurred in Australian-born men aged 21 years or younger (from four of 13 31%, 95% CI 9–61% to none of 25; ptrend <0·0001). Genotypes 16 and 18 decreased (adjusted prevalence ratio PR 0·32, 95% CI 0·14–0·74; p=0·008) but not genotypes 6 and 11 (adjusted PR 0·50, 0·16–1·56; p=0·234) in the postvaccination period among men who had arrived in Australia within 2 years from countries with a bivalent vaccine (2vHPV) programme (England, Scotland, Wales, Cook Islands, Northern Ireland, or the Netherlands), compared with the prevaccination period. No change was noted in 4vHPV genotypes in men born overseas in other countries. Interpretation The marked reduction in prevalence of 4vHPV genotypes among mainly unvaccinated Australian-born men suggests herd protection has occurred from the female vaccination programme. Additionally, the decline in genotypes 16 and 18, but not genotypes 6 and 11, among overseas-born men predominantly from countries with a 2vHPV vaccine programme suggests that these men received benefits from herd protection for genotypes 16 and 18 from their vaccinated female partners in their own countries. These reductions could translate to reductions in HPV-related malignant conditions in men, even in countries with female-only vaccination programmes. Funding The Australian National Health and Medical Research Council Program.
Summary Background The national quadrivalent human papillomavirus (4vHPV) vaccination programme was launched in Australia in April, 2007. In this study, we aimed to explore the prevalence of ...vaccine-targeted human papillomavirus (HPV) types contained in the 4vHPV and nine-valent HPV (9vHPV) vaccines detected in young women diagnosed with chlamydia. Methods In this cross-sectional study, we identified specimens from women aged 25 years or younger who attended the Melbourne Sexual Health Centre (Melbourne, VIC, Australia) diagnosed with chlamydia. We calculated the prevalence of 4vHPV types (6, 11, 16, and 18) and the extra five 9vHPV types (31, 33, 45, 52, and 58 alone) excluding 4vHPV types, stratified by Australian financial year (and according to the prevaccination and postvaccination periods) and self-reported vaccination status, for all women, Australian-born women, Australian-born women aged 21 years and younger, and overseas-born women. We calculated adjusted prevalence ratios using binomial log linear regression. Findings Between July 1, 2004, and June 30, 2014, we included 1202 women. The prevalence of 4vHPV types in Australian-born women decreased during this period (HPV 6 and 11: 2004–05 nine 16%, 95% CI 8–28 of 56 vs 2013–14 one 2%, 0–9 of 57, p<0·0001; HPV 16 and 18: 17 30%, 19–44 vs two 4%, 0–12, p<0·0001). In Australian-born women aged 21 years and younger, HPV 6 and 11 prevalence remained at 0% for all years after 2008–09, and we detected HPV 16 and 18 in 5% or less of samples for the same period. In unvaccinated Australian-born women, we noted a significant decrease in 4vHPV types from 66 (41%, 95% CI 34–49) of 160 in the prevaccination period (from July 1, 2004, to June 30, 2007) to five (19%, 6–38) of 27 in the postvaccination period (July 1, 2007, to June 30, 2014; p=0·031), but not in the 9vHPV types, excluding 4vHPV (36 23%, 95% CI 16–30 vs seven 26%, 11–46; p=0·805). Interpretation The three-dose vaccination coverage was sufficient for the 4vHPV types to almost disappear in Australian-born women aged 21 years or younger within 3 years of introduction of the national HPV vaccination programme. We noted strong herd protection, with a significant decrease in the prevalence of 4vHPV in unvaccinated women. The 4vHPV vaccination programme in Australia has been successful at protecting women against 4vHPV types. Funding Australian National Health and Medical Research Council.
Summary Background Men who have sex with men (MSM) have an increased risk of anogenital human papilomavirus (HPV) infection, which can lead to HPV-related anogenital lesions such as warts, anal ...intraepithelial neoplasia, and anal cancer. Some of these HPV types are preventable with vaccines. We aimed to describe the incidence of anal, penile, and oral HPV infection, and to estimate the site-specific transmission probability per partner, for teenage MSM. Methods In our observational cohort study, we enrolled teenage MSM (aged 16–20 years) with low sexual exposure and a low prevalence of HPV in Melbourne (VIC, Australia). At baseline, 3, 6, and 12 months, we took a swab from the anal canal, and participants self-collected a swab from the penis and an oral rinse. Our primary outcome was definite and probable incident HPV infection of the anus, penis, or mouth at any time in the 12 months from baseline, assessed through the presence of HPV DNA. We defined definite incident HPV infection as the same HPV type detected more than once from the same site in men who had a negative HPV test at baseline. We defined probable incident HPV infection as only one positive test. We estimated the probability of HPV transmission per partner using HPV prevalence in MSM with a similar age to partners of men in our cohort. This study is registered at the Australian New Zealand Clinical Trials Registry and ClinicalTrials.gov , numbers ACTRN12611000857909 and NCT01422356. Findings We enrolled 200 MSM aged 16–20 years (median 19 years IRQ 18–20; range 16–20) between Sept 20, 2010, and Aug 24, 2012. Over the 12 month follow-up period, we detected 48 definite (107 possible) HPV infections in the anus, ten definite (34 possible) HPV infections on the penis, and no definite (six possible) infections in the mouth. Definite incidence rate per 100 person-years for any anal HPV infection was 57 (95% CI 46–68), and for any anal HPV type in the quadrivalent vaccine was 33 (23–44). Definite incidence rate per 100 person-years for any penile HPV was 12 (6–21) and for any HPV type in the quadrivalent vaccine was 5 (1–12). Estimated probabilities of HPV transmission from the penis to the anus were significantly higher than were those from the anus to the penis (p<0·05 for all HPV types in the quadrivalent vaccine). Interpretation High incidence rates suggest that the vaccination coverage in MSM will need to be high. The transmission estimates will inform HPV modelling. Funding Merck.
