Oral oncogenic human papillomavirus infections in men cleared more slowly when already present at detection than when newly acquired, according to findings from a three-country cohort study. Most new infections resolved within months, while older men and those reporting frequent oral sex were less likely to clear infections.
Researchers analyzed 739 oral oncogenic human papillomavirus (HPV) infections—533 newly acquired and 206 previously detected—among 589 men who were followed for nearly 45 months. Among newly acquired infections, 78% cleared within 6 months, while 7% persisted beyond 24 months. In contrast, 47% of previously detected infections cleared within 6 months, and 24% persisted longer than 24 months. For HPV16, 14% of new infections and 22% of existing infections persisted beyond 24 months.
Men older than 39 years and those who reported giving oral sex 7 or more times in the past 6 months were less likely to clear an infection. Men who reported 3 to 11 and more than 12 female sex partners were more likely to clear a previously detected oncogenic infection. Overall, higher levels of sexual activity were a key factor associated with a lower likelihood of oral oncogenic HPV clearance across both infection types. This pattern was most evident when persistence was assessed at 6 months and 12 months. Although earlier work, including prior analyses from the HPV Infection in Men (HIM) Study, found similar associations with acquisition, the current data suggest that increased exposure through sexual activity may represent repeated exposure to the virus. Low seroconversion rates in men and a high risk of recurrence with genital HPV infection point to a possible pathway between frequent sexual exposure and oral HPV persistence.
A lower proportion of Black men (13%) and men of other race (29%) had an infection that persisted at least 6 months compared with 50% of White men. A threefold higher risk of 12-month persistence was observed among men reporting “Other” race, and non-Hispanic men also showed higher short-term persistence. The authors noted that although race was not associated with overall likelihood of clearance in Cox models, these racial differences in persistence warrant further study.
Smoking was not associated with overall clearance but was linked to 6-month persistence of incident infections. However, this association disappeared at 12 months. No statistically significant differences in clearance were observed between countries.
Among infections that lasted at least 6 months, clearance patterns were similar for new and existing infections during the first 18 months, after which newly acquired infections cleared more quickly. Median infection duration for incident infections that lasted at least 6 months increased with age and reached about 34 months in men older than 42 years compared with less than 18 months in younger men. “Both infection types have a high proportion that resolve within 6 months (transient), with more than 95% of incident infections cleared at 78 months of follow-up as compared with 85% of prevalent infections,” wrote Anna R. Giuliano, PhD, of the Center for Immunization and Infection Research in Cancer at the Moffitt Cancer Center in Tampa, Florida, corresponding author of the study, with colleagues.
The authors discussed vaccination as an important public-health context for their findings. Many men remain unvaccinated, and although vaccination programs in high-income countries target both sexes, low- and middle-income nations often vaccinate only young females. Vaccination coverage is lower in males (6%) than in females globally (20%), leaving multiple male cohorts unprotected. Previous modeling suggested limited benefit of vaccination in men beyond 26 years of age; however, the persistence of infections in older men observed in this study indicates that vaccination through age 45 may still reduce risk. Similar findings from D’Souza et al. and other cohorts support consideration of extended male vaccination to prevent persistent oral HPV infections, and the researchers for this study wrote that vaccination at older ages warrants further investigation.
The researchers followed 3,137 men aged 18 to 70 years from Brazil, Mexico, and the United States who participated in the HIM Study between 2005 and 2016. Participants provided oral gargle specimens every 6 months, which were tested for 25 HPV genotypes using SPF10 PCR-DEIA-LiPA25. Clearance was defined as 2 consecutive negative tests for the same HPV type. The researchers used Kaplan–Meier methods to estimate clearance probability and Cox regression models to identify predictors of clearance.
They noted several limitations. Behavioral data were self-reported, which may have introduced recall bias. The 6-month testing intervals limited the precision of determining exact infection acquisition and clearance times. Oral gargle samples, though standard for detecting HPV in cancer-free populations, did not specifically target the oropharyngeal region, which may have influenced detection accuracy.
Full disclosures can be found in the study.
Source: Nature Communications