Higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human Papillomavirus Clearance in Uncircumcised Kenyan Men

Abstract

Background Whether higher penile human papillomavirus(HPV) viral load is associated with a lower rate of HPV clearance remains unknown. Objectives We examined the association between penile HPV16 and HPV18 viral load and subsequent HPV clearance in uncircumcised Kenyan men. Study Design Participants were HIV-seronegative, sexually active, 18–24 year old men randomized to the control arm of a male circumcision trial in Kisumu, Kenya. Men provided exfoliated penile cells from two anatomical sites (glans/coronal sulcus and shaft) every 6 months for 2 years. GP5+/6+ polymerase chain reaction(PCR) was used to identify 44 HPV-DNA types. HPV viral load testing was conducted using a LightCyler real-time PCR assay; viral load was classified as high(> 250 copies/scrape) or low(≤250 copies/scrape), for non-quantifiable values. The Kaplan-Meier method and Cox regression modelling were used to examine the association between HPV viral load and HPV clearance. Results A total of 1097 men, with 291 HPV16 and 131 HPV18 cumulative infections over 24 months were analyzed. HPV clearance at 6 months after first HPV detection was lower for high versus low viral load HPV16 infections in the glans [adjusted hazard ratio (aHR) = 0.65(95% confidence interval, 0.46-0.92)] and shaft (aHR=0.44(0.16-0.90), and HPV18 infections in the glans [aHR=0.05(0.01-0.17)]. Discussion High versus low HPV viral load was associated with reduced HPV clearance for HPV16 infections in the glans and shaft, and for HPV18 infections in the glans, among young uncircumcised men. Reduced clearance of high viral load HPV16 and HPV18 infections in men may increase HPV transmission to their female partners as well as enhance the development of penile lesions in comparison to men with low viral load HPV infections.

Does Male Circumcision Reduce Women's Risk of Sexually Transmitted Infections, Cervical Cancer, and Associated Conditions?

“…Decreased viral “ shedding ” among men was suggested as a reason for the reduced acquisition of HPV in female partners of the circumcised men (160). In uncircumcised men with a high viral load, clearance of high-risk HPV16 and HPV18 was lower, thus increasing risk of HPV transmission to female partners (112). In addition to the lower risk of oncogenic HPV infection, female partners of circumcised men in the Ugandan RCT had lower HPV viral loads that were contributed entirely by incident new high-risk HPV infections during the 24 months follow-up period (PRR = 0.66; 95% CI 0.50–0.87, P = 0.003) (113).…”

Recent advances in understanding and preventing human papillomavirus-related disease

“…Higher viral load was also associated with decreased HPV clearance rates in uncircumcised males and homosexual men who smoke 40, 41 . Methylation of CpG sites in HPV DNA is a marker of persistent infection, particularly for HPV-16, that may have utility in triage: in a large randomised controlled trial, methylation triage on cervicovaginal self samples was non-inferior to cytology triage on clinician-taken samples for the detection of high-grade CIN 42 .…”

“…Recently, the predictive value of HPV viral load as a measure of persistence has been investigated: several studies have shown that high baseline HPV-16 and -18 viral load or viral load increase over time are associated with persistent infections 34 – 36 and low viral load, or a >100-fold decline over time, is associated with clearance 37 – 39 . Higher viral load was also associated with decreased HPV clearance rates in uncircumcised males and homosexual men who smoke 40 , 41 . Methylation of CpG sites in HPV DNA is a marker of persistent infection, particularly for HPV-16, that may have utility in triage: in a large randomised controlled trial, methylation triage on cervicovaginal self samples was non-inferior to cytology triage on clinician-taken samples for the detection of high-grade CIN 42 .…”

Development and interlaboratory agreement of real-time PCR for HPV16 quantification in liquid-based cervical samples

“…Moreover, a cutoff value of 22,000 copies/10 3 cells permits to identify among HPV16 infected women those with a high grade lesion with a specificity of 90% [20] . Furthermore, HPV16 load may represent a risk factor for persisting infection [25] , [26] , [27] , [28] or progression toward a high grade cervical lesion [29] , [30] . In a retrospective longitudinal study, a HPV16 viral load of 200 copies/10 3 cells was shown to represent a relevant cutoff above which women with no or mild abnormalities of the cervix present a high risk to develop an incident CIN2/3 at 18 months [29] .…”