Presence of human papillomavirus in semen of healthy men is firmly associated with HPV infections of the penile epithelium.

Objective: To study the source of human papillomavirus (HPV) in semen.

Design: Observational study (CCMO-NL3248800010).

Setting: Academic hospital-based laboratory.

Patient(s): Healthy male volunteers (n = 213).

Intervention(s): One penile scrape and three semen samples were obtained per participant for HPV-DNA testing by both GP5+/6+ polymerase chain reaction (PCR) and SPF10-PCR to detect moderate/high and low viral loads, respectively; flat penile lesions (FPL) were detected by penoscopy.

Main Outcome Measure(s): HPV-DNA presence in semen and penile scrapes, and the presence of FPL.

Result(s): HPV-DNA at moderate/high viral loads (i.e., GP5+/6+ PCR-positive) was detected in ≥1 semen sample(s) in 27% of participants. Most men with moderate/high viral loads in the penile scrape also had moderate/high viral loads in semen (85%). Men with a HPV-negative penile scrape were very unlikely to have moderate/high viral loads in semen (3%). The presence of HPV in semen was associated with the presence of HPV in the penile scrape also on a genotype-specific level. Having FPL was a risk factor for HPV presence in semen.

Conclusion(s): HPV-DNA presence in semen of healthy men is common and associated with HPV infections of the penile epithelium. HPV-DNA presence in semen may result from desquamation of HPV-infected penile cells.