Incident HPV infections were common among Kenyan men, with an IR of almost 50/1000 person-months. The incidence of high-risk HPV infections in the glans was higher than the incidence of low-risk infections in the glans and of HPV infections in the shaft. The strongest risk factors for overall HPV incidence were having at least two sexual partners in the year prior to enrolling in the RCT and bathing less frequently than daily.
This is the largest follow-up study of HPV infection, to our knowledge, among uncircumcised men to date. It is also one of the first to determine risk factors for HPVacquisition among men from sub-Saharan Africa. A sensitive GP5+/6+ PCR assay was used to detect a wide range of HPV types in a central laboratory, and separate HPV laboratory testing for glans and shaft specimens allowed for stratified analyses by anatomical site. Novel parametric frailty models were used to assess several potential risk factors for HPV acquisition, which allow for the analysis of clustered survival data using arbitrary censoring.25
The IR of 49.3/1000 person-months found in our study is higher than previously reported IR estimates among men, ranging from 17.9/1000 person-months among military men from Mexico to 38.4/1000 person-months among men from Brazil, Mexico and the USA.6–8, 14
The higher IR in our study could be due in part to the longer duration of 1 year between visits in the study from Mexico,8
which may have underestimated the true IR, and the lower percentage of uncircumcised men in the international and US studies.6, 7, 14
Our IR estimate for high-risk HPV infection in the glans (27.3/1000 person-months, equivalent to 32.8/100 person-years) was slightly higher than the corresponding IR in the glans among HIV-negative, married men participating in the control arm of an RCT of male circumcision in Uganda (IR=29.4/100 person-years).10
The slightly higher IR found in our Kenyan study could be due to differences in age and marital status as the Uganda study had a higher median age and only included married participants.
HPV16, the most prevalent HPV type in this population (9.9%), also had the highest incidence (10.9/1000 person-months). A high incidence of HPV16 has been similarly reported in other studies among both men6, 7, 9, 14
The high rate of acquisition of HPV16 has a clear implication for increasing cancer risk among men and their sexual partners, as HPV16 is the most common HPV type found in penile cancer among men;2
cervical, vulvar and vaginal cancers among women;1, 27
and in anal and oropharyngeal cancers in both sexes.3, 4
Penile HPV IRs in our study were higher in the glans specimen, including the inner foreskin, compared with the shaft (HR=2.1; 95% CI 1.7 to 2.4). Our results are in contrast to the findings of a US study of 240 men.7
In this highly circumcised US population, the cumulative probability of incident HPV infection did not differ by anatomical site (44.3% in glans vs 45.4% in shaft). Among uncircumcised men, there may be a larger disparity in HPV acquisition by penile site, potentially attributable to keratinisation of the glans epithelium and removal of the inner foreskin after circumcision.
Our findings indicate that less frequent bathing was a strong risk factor for HPV incidence. These findings are similar to those in a previous report among this population that found less frequent bathing to be the strongest risk factor for cross-sectional HPV point-prevalence.20
To our knowledge, no other studies of penile HPV acquisition among men have investigated overall bathing frequency as a potential risk factor. Three studies of penile HPV infection reported no association with the time since last bath or shower7
nor with genital washing after intercourse.8, 28
Similarly, we did not find an association between the number of hours until bathing after sex and HPV acquisition. Little is known about the effect of improved penile hygiene on HPV infection. While bathing more frequently may not completely prevent HPV infection in men, our findings provide evidence that more frequent bathing is associated with a decreased risk of HPV acquisition. To assess whether more frequent bathing reduces incident HPV infections, RCTs should be conducted to examine the effect of male bathing on incident HPV infections. Our results indicated that men who reported a higher number of recent sexual partners also had higher HPV IRs, as was found in previous studies of HPV incidence in men.7, 9
We also found a slightly elevated risk of overall HPV incidence among men who were employed, but this association was not associated with high-risk HPV incidence.
The 6-month interval between each visit was a limitation of this study as participants in our study could have acquired a new HPV infection and cleared it before their subsequent follow-up visit, potentially underestimating HPV incidence in our study. β-Globin positivity was also relatively low in our study; however, it has been previously indicated that β-globin-PCR-negative samples may contain detectable HPV as HPV copies may often exceed those of the β-globin gene.20
When restricting our analyses to β-globin-positive samples, IRs for overall HPV in the glans and shaft (47.9 and 22.4/1000 person-months, respectively) were similar to the IRs observed in the glans and shaft among all samples (44.4 and 21.6/1000 person-months, respectively). Bathing frequency and number of recent sexual partners also remained strong risk factors of HPV incidence among β-globin-positive samples.
The generalisability of our findings may be somewhat limited, given that participants were a select population of primarily unmarried, uncircumcised men with at least a secondary education who met eligibility criteria for an RCT that entailed circumcision. Uncircumcised men may be more likely to acquire HPV infections than circumcised men10, 18
and risk factors, such as less frequent bathing, may be modified by circumcision status; thus, caution should be taken when comparing our findings with those of circumcised populations.
In conclusion, we found a high incidence of high-risk HPV in the glans among uncircumcised men. Male circumcision has been found to be an effective intervention for decreasing high-risk HPV acquisition among men.10, 18
For men who remain uncircumcised, reducing the number of recent sexual partners and improving penile hygiene could potentially reduce HPV acquisition.