David G. Regan

Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data

BACKGROUND Quadrivalent human papillomavirus (HPV) vaccine has high efficacy in clinical trials but no reports describe its effects at a population level. From July, 2007, Australia was the first country to fund a vaccination programme for all women aged 12-26 years. We established a national surveillance network in Australia and aimed to identify trends in diagnoses of genital warts in 2004-09. METHODS We obtained standardised data for demographic factors, frequency of genital warts, HPV vaccination status, and sexual behaviour for new patients attending eight sexual health services in Australia between January, 2004, and December, 2009. We used χ² analysis to identify significant trends in proportions of patients diagnosed with warts in periods before and after vaccination began. Our primary group of interest was female Australian residents who were eligible for free vaccination, although data were assessed for patients ineligible for free vaccination, including women older than 26 years of age, non-resident women, and men. FINDINGS Among 112 083 new patients attending sexual health services, we identified 9867 (9%) cases of genital warts. Before the vaccine programme started, there was no change in proportion of women or heterosexual men diagnosed with genital warts. After vaccination began, a decline in number of diagnoses of genital warts was noted for young female residents (59%, p(trend)<0·0001). No significant decline was noted in female non-residents, women older than 26 years in July, 2007, or in men who have sex with men. However, proportionally fewer heterosexual men were diagnosed with genital warts during the vaccine period (28%, p(trend)<0·0001), and this effect was more pronounced in young men. By 2009, 65·1% of female Australian residents who were eligible for free vaccine reported receipt of quadrivalent or unknown HPV vaccine. INTERPRETATION The decrease in frequency of genital warts in young Australian women resulting from the high coverage of HPV vaccination might provide protective effects in heterosexual men through herd immunity. FUNDING CSL Biotherapies.

Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data

Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Design Trend analysis of national surveillance data. Setting Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Participants Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Main outcome measure Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Results Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period—from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period—from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. Conclusions The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.

Head and neck cancer in Australia between 1982 and 2005 show increasing incidence of potentially HPV-associated oropharyngeal cancers

Background:Although tobacco- and alcohol-associated head and neck cancers are declining in the developed world, potentially human papillomavirus (HPV)-associated oropharnygeal cancers are increasing.Methods:We analysed oropharyngeal and oral cavity cancer rates in Australia in 1982–2005. Cancers from the oropharynx (base of tongue, tonsil and other specific oropharyngeal sites) were classified as potentially HPV associated (n=8844); cancers in other oral cavity and oropharyngeal sites not previously associated with HPV were classified as comparison (n=28 379).Results:In 2000–2005, an average of 219, 159 and 110 cancers of the tonsil, base of tongue and other oropharyngeal sites were diagnosed annually, with incidences of 1.09 (95% CI: 1.03, 1.15), 0.79 (95% CI: 0.74, 0.84) and 0.55 (95% CI: 0.50, 0.59) per 100 000, respectively. An average of 1242 comparison cancers were diagnosed annually (6.17 (95% CI: 6.03, 6.31) per 100 000). In 1982–2005, there were significant annual increases in tonsil (1.39% (95% CI: 0.88, 1.92%)) and base of tongue cancers in males (3.02% (95% CI: 2.27, 3.78%)) and base of tongue cancer in females (3.45% (95% CI: 2.21, 4.70%)). There was a significant decrease in comparison cancers in men (−1.69% (95% CI: −1.96, −1.42%)), but not in females.Conclusion:Potentially HPV-associated oropharyngeal cancer in Australia is increasing; the impact of HPV vaccination on these cancers should be monitored.

Importance of promoting HIV testing for preventing secondary transmissions: modelling the Australian HIV epidemic among men who have sex with men.

BACKGROUND We address the research questions: (i) what proportion of new HIV infections is transmitted from people who are (a) undiagnosed, (b) in primary HIV infection (PHI), (c) on antiretroviral therapy?; and (ii) what is the expected epidemiological impact of (a) increasing the proportion of newly acquired HIV infections receiving early treatment, and (b) increasing HIV testing rates? METHODS We used a mathematical model to simulate HIV transmission in the population of men who have sex with men (MSM) in Australia. We calibrated the model using established biological and clinical data and a wide range of Australian MSM epidemiological and behavioural data sources. RESULTS We estimate that ~19% of all new HIV infections are transmitted from the ~3% of Australian HIV-infected MSM who are in PHI; ~31% of new HIV infections are estimated to be transmitted from the ~9% of MSM with undiagnosed HIV. We estimate that the average number of infections caused per HIV-infected MSM through the duration of PHI is ~0.14-0.28. CONCLUSIONS The epidemiological impact of increasing treatment in PHI would be modest due to insufficient detection of newly-infected individuals. In contrast, increases in HIV testing rates could have substantial epidemiological consequences. The benefit of testing will also increase over time. Promoting increases in the coverage and frequency of testing for HIV could be a highly-effective public health intervention, but the population-level impact of interventions based on promoting early treatment of patients diagnosed in PHI is likely to be small. Treating PHI requires further evaluation of its long-term effects on HIV-infected individuals.

A cost-effectiveness analysis of adding a human papillomavirus vaccine to the Australian National Cervical Cancer Screening Program

BACKGROUND The cost-effectiveness of adding a human papillomavirus (HPV) vaccine to the Australian National Cervical Screening Program compared to screening alone was examined. METHODS A Markov model of the natural history of HPV infection that incorporates screening and vaccination was developed. A vaccine that prevents 100% of HPV 16/18-associated disease, with a lifetime duration of efficacy and 80% coverage offered through a school program to girls aged 12 years, in conjunction with current screening was compared with screening alone using cost (in Australian dollars) per life-year (LY) saved and quality-adjusted life-year (QALY) saved. Sensitivity analyses included determining the cost-effectiveness of offering a catch-up vaccination program to 14-26-year-olds and accounting for the benefits of herd immunity. RESULTS Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of

Coverage Is the Key for Effective Screening of Chlamydia trachomatis in Australia

51 103 per LY and

Trends in anal cancer in Australia, 1982–2005

18 735 per QALY, assuming a cost per vaccine dose of

Serosorting may increase the risk of HIV acquisition among men who have sex with men.

115. Results were sensitive to assumptions about the duration of vaccine efficacy, including the need for a booster (

Sampling and sensitivity analyses tools (SaSAT) for computational modelling

68 158 per LY and

Molecular approaches to enhance surveillance of gonococcal antimicrobial resistance

24 988 per QALY) to produce lifetime immunity. Accounting for herd immunity resulted in a more attractive ICER (