Introduction

Human papillomaviruses (HPV) constitute several genera. The vast majority of previous research on HPV has focused on the genusAlphapapillomavirus , whose types infect the mucosal epithelium and are an established cause of anogenital and some oropharyngeal cancers.1 HPVs of the genus Betapapillomavirusnormally infect the cutaneous epithelium.2Comparatively much less research has been done on the epidemiology of infections with betapapillomaviruses. However, growing evidence suggests that betapapillomaviruses may play a role in the development of skin cancers, and may be associated with the risk of a subset of head and neck cancers.1,3-5 More research on the incidence, transmission, and risk factors for betapapillomavirus infection is warranted.
While betapapillomaviruses were first isolated from the skin and are widely considered to prefer infecting the cutaneous epithelium, there is substantial evidence that they are also able to infect the mucosal epithelium.4,6 The detection of betapapillomaviruses in oral and genital samples suggests they are able to infect these sites along with alphapapillomaviruses.7-12 There is therefore the potential for biological interactions between HPV types of different genera. While co-detection patterns and the potential for interactions between HPV types within the alphapapillomavirus genus has been the topic of substantial previous research,13-16there is scant research on cross-genus co-detection patterns and interactions. Biological interactions and co-detection patterns between different HPV types are important to study from a public health perspective due to the risk of genotype replacement following widespread implementation of HPV vaccination programs.17 Although there is currently little evidence that genotype replacement has occurred for alphapapillomaviruses,18 the potential for interactions with other HPV genera has not been studied.
We had previously found a fairly high prevalence of betapapillomaviruses in cervicovaginal samples of the Ludwig-McGill cohort study of HPV natural history.19 While we examined a number of putative risk factors, the only variable that was associated with betapapillomavirus prevalence in univariate analyses was lifetime number of sex partners; curiously, we found a lower betapapillomavirus prevalence among women with four or more lifetime sex partners. We also did not find that alphapapillomaviruses and betapapillomavirus co-detection patterns deviated significantly from expectations under independence. However, these analyses were underpowered as we only tested a restricted number of samples for betapapillomaviruses, and only looked at prevalent but not incident co-detections.
The objective of the current study was to assess a larger number of samples of the Ludwig-McGill cohort study than previously tested to i) examine whether there is evidence of biological interactions between alphapapillomaviruses and betapapillomaviruses, and ii) assess risk factors for betapapillomavirus genital prevalence and incidence.