In our study, the prevalence of anal hr-HPV infection among MSM cohort was 58.5% [54.7–62.3], and the most frequently detected hr-HPV genotypes in order were HPV-52 (18.5%), HPV-16 (16.9%), and HPV-58 (15.7%) among them. Our previous study conducted 10 years ago in the HIV-infected MSM cohort identified prevalence of hr-HPV infection as high as 75.9%, and the most frequent hr-HPV genotypes in order were HPV-58 (30.2%), HPV-16 (28.8%) and HPV-52 (22.2%)9. Considered together, these 3 genotypes are predominant hr-HPV genotypes among Japanese MSM throughout in this decade. Our study also revealed similar prevalence among HIV-infected subjects 67.0% [62.5–71.3], while HIV-uninfected subjects had a lower rate of 40.6% [34.1–47.4].The high prevalence with hr-HPV in MSM are almost concurrent with those reported in other Asian countries, but the distribution of hr-HPV genotypes was somewhat different4,14,15. The prevalence of HPV infection was 85.2% in Taiwan, 82.7% in China and 85% in Thailand, while most frequent HPV genotypes were HPV-16, HPV-51 and HPV-52 in Taiwan and Thailand, HPV-16 and HPV-18 in China4,14,15.
All of 9 valent HPV vaccine covered genotypes (genotypes 16, 18, 31, 33, 45, 52 and 58 are high-risk HPV genotypes, while genotypes 6 and 11 are low-risk HPV genotypes) were not rarely (> 5%) identified in the study participants (See supplementary Fig S1 online). Moreover, most of HPV infected subjects (312/377) possessed at least one of the 9 valent vaccine covered genotypes. These results indicate that vaccine preventable genotypes are currently common hr-HPV among Japanese MSM.
Even more interestingly, it was clearly documented for the first time in Japan in the present study that the incidence of abnormal cytology was positively correlated with the number of HPV genotypes detected (Fig. 2b, Table 2), as was discussed in a previous study14. On the other hand, the incidence of abnormal cytology was not greatly influenced by the difference in genotypes (Fig. 2a). Considered together, HPV vaccination could be recommended even for those who were already infected with some hr-HPV genotypes to prevent the further acquisition of different vaccine preventable HPV genotypes, as recommended in previous study16. Another associated risk factor for abnormal cytology was HIV infection, although our participants with HIV-infection are all well-controlled by anti-retroviral therapy (ART). However, it is not clear from the present study of the cross-sectional design whether HIV causes impaired clearance of the HPV infection, or HIV-infected individuals reacquire HPV more frequently.
Table 2
Multiple logistic regression analysis to determine the factors associated with abnormal anal cytology
HPV positive individuals (n = 377) | Univariate analysis | Multivariate analysis |
OR [95% CI] | P value | OR [95% CI] | P value |
Age (+ 1 year) | 1.03 [1.01–1.06] | .008 | 1.03 [.99-1.06] | .094 |
HIV infection | 12.06 [2.90-50.18] | .001 | 6.52 [1.52–28.46] | .012 |
Number of detected hr-HPV genotypes | 1.65 [1.38–1.97] | < .001 | 1.57 [1.30–1.90] | < .001 |
100% use of condom | 1.35 [.67-2.72] | .395 | | |
No. of lifetime sexual partner | 2.45 [1.00-5.99] | .051 | | |
Past treatment history of STI | 1.62 [.77-3.41] | .203 | | |
There are some limitations to be considered in the present study. First, this was a cross-sectional study, and it is difficult to assess whether the HPV infection has been a transient infection or a persistent one, or a re-infection. Second, this study only analyzed hr-HPV genotypes, therefore not all genotypes were assessed. Third, cytology results for HIV-uninfected subjects were reported only using pap smear, then translated to Bethesda system using previously reported relationship of the two systems12.
In conclusion, we found that hr-HPV, especially 9 valent HPV vaccine preventable HPV, was highly prevalent among MSM in Japan. Also, it was shown that increased number of hr-HPV genotypes were strongly associated with anorectal pre-cancer. Universal HPV vaccination for Japanese MSM should be considered to prevent HPV related malignancy, although further studies is needed for assessing health impact and cost-effectiveness of nine-valent HPV vaccination.