Human Papillomavirus Community in Healthy Persons, Defined by Metagenomics Analysis of Human Microbiome Project Shotgun Sequencing Data Sets

Abstract

Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCEThis nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high-and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections. Human papillomaviruses (HPVs) are a group of doublestranded, nonenveloped, small DNA viruses that are widely prevalent among human populations. To date, 176 types of HPV isolated from different body sites have been identified and collected in two HPV databases (http://pave.niaid.nih.gov, http: //www.hpvcenter.se) searched on 30 November 2013, and the number is growing (1-3).HPV is a well-established cause of cervical cancers (4-8). It is well known that long-term persistence of HPV infection is a necessity for development of cervical cancers, and the majority of women with HPV infection show a "healthy" phenotype for most of their lifetime (9). HPV infection has been linked worldwide to several cancers outside the reproductive system, including cancers of the oropharynx, pharynx, larynx, tonsils, and so on (10-15). Around 30 HPV types, notably types 16 (i.e., HPV16) and 18, which showed a strong association with cervical cancers, were designated high-or low-risk types. Although more and more nonrisk types have been observed from various human samples by traditional HPV detection methods (16-18), our understanding of HPV prevalence has been limited by the narrowed spectrum of amplicon-based me...

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

“…compositions of human skin have been characterized at multiple sites in healthy individuals (The Human Microbiome Project Consortium, 2012;Gao et al, 2007;Paulino et al, 2008;Grice et al, 2009;Gao et al, 2010;Ursell et al, 2012;Blaser et al, 2013;Findley et al, 2013;Fitz-Gibbon et al, 2013;Nakatsuji et al, 2013), we have limited understanding of the skin virome (Foulongne et al, 2012;Ma et al, 2014). Whether bacteriophages have a role in skin health and disease by modulating the diversity and dynamics of the bacterial community on the skin is poorly understood.…”

“…They are a reservoir of diversity-generating elements (Rohwer and Thurber, 2009) and regulate both the abundance and diversity of their bacterial hosts by predation (Suttle et al, 1990;Waterbury and Valois, 1993;Rohwer, 2003;Rodriguez-Valera et al, 2009). Although the skin bacterial community has been studied by several groups (Gao et al, 2007;Costello et al, 2009;Grice et al, 2009;Kong et al, 2012;The Human Microbiome Project Consortium, 2012;Blaser et al, 2013;Fitz-Gibbon et al, 2013;Nakatsuji et al, 2013), relatively few studies have characterized the skin viral community (Foulongne et al, 2012;Ma et al, 2014;Wylie et al, 2014). In particular, the composition and dynamics of bacteriophages and their interactions with bacterial hosts on the skin are not well understood.…”

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

“…HPV constitute an important part of the normal human skin virome 6, 7, 19, 20. There is strong evidence from laboratory studies to suggest that HPV plays a role in cSCC carcinogenesis, principally through synergy with UVR 13, 14, 15.…”

“…The virome component of the human microbiome is known to play an important role in disease,4, 5 and HPV is particularly prevalent in the normal skin virome 6, 7. HPVs are double‐stranded DNA viruses that are classified into 5 genera (α, β, γ, μ, and ν) 8, 9.…”

“…βPVs are ubiquitous, with more than 90% of people carrying these viruses as part of their normal skin virome 7, 19, 20. Hair follicles are the likely reservoir 18.…”