The role of human papillomavirus (HPV) viral load in penile HPV infection and clearance among young Kenyan men

Senkomago, Virginia

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March 20, 2019

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Senkomago, Virginia
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology

Abstract

Persistent infections with human papillomavirus (HPV) types 16 and 18 are causes of cervical cancer in women and various penile squamous cell carcinomas (SCC) in men. Male circumcision has been found to be protective against penile HPV, but the association between circumcision and HPV viral load remains unclear. Additionally, the role of HPV viral load in HPV persistence and subsequent development of penile SCC is unknown. An HPV-ancillary study, nested within a randomized controlled trial (RCT) of male circumcision, was conducted in Kisumu, Kenya. Eligible participants were HIV seronegative, uncircumcised and aged 18-24. Penile swabs were collected from glans and shaft sites every 6 months for 24 months. GP5+/6+ PCR was used to identify HPV DNA types. HPV viral load was measured with LightCyler real-time PCR and classified as high (>250copies/scrape) or low (≤250copies/scrape). Of 2,299 men with HPV baseline results, 1,159 were randomized to immediate circumcision and 1,140 to the control arm and asked to remain uncircumcised until study end. The acquisition of high viral load infections in the glans was lower in the circumcision than control arm for HPV16 [Hazard Ratio(HR)=0.32(0.20-0.49)] and HPV18 [HR=0.34(0.21-0.54)]. For prevalent high viral load infections in the glans at baseline, risk of persistence to 6 months was lower in the circumcision arm [0.20(0.09-0.34)] than control arm [0.55(0.39-0.68)] for HPV16 and HPV18 [0.17(0.05-0.34) and 0.50(0.25-0.71), respectively]. In uncircumcised men, the hazard of HPV16 clearance at 6 months after first HPV16 detection was found to be lower for high versus low viral load incident infections in the glans [adjusted hazard ratio (aHR) =0.58 (95%confidence interval, 0.36-0.93)]. HPV16 and HPV18 clearance in the shaft was comparable for high and low viral load infections. Male circumcision reduces the acquisition and possibly enhances the clearance of high viral load HPV16 or HPV18 infections in the glans, and thus could potentially reduce HPV transmission to women. The reduced rate of high versus low viral load HPV16 clearance in uncircumcised men could be associated with increased development of penile SCC, and may also explain the increase in HPV16 transmission in men with high viral load to their female partners.

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