Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study

Abstract

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%], p_trend=0·008), 16 and 18 (from 13% [95% CI 7-22%] to 3% [1-6%], p_trend<0·0001), and 4vHPV-targeted genotypes (from 22% [95% CI 14-33%] to 6% [3-10%], p_trend<0·0001). Prevalence of non-vaccine-targeted genotypes increased from 16% [95% CI 9-26%] to 22% [17-29%], p_trend<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%], p_trend<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; p_trend<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.