The present study investigated the detection of HPV DNA in oral rinse samples using PCR primers that efficiently amplify α-, β-, and γ-HPV types. Because the oral cavity has not been studied as extensively as the cervical region, detection of oral and cervical HPV infections using identical methods in one experienced laboratory indicated that the oral cavity contains a large number of HPV types that were not previously recognized. The HPV types detected in the oral cavity were predominantly from the β- and γ-HPV genera, which were previously considered nearly exclusively skin types. The HPV types identified in the oral cavity were unlikely to be contaminants, since they were detected with relatively high signal strength (data not shown) and encompassed many novel types. Former surveys of oral HPV infection mainly focused on high-risk genital α-HPV type infections (eg, HPV type 16) that are associated with oral and oropharyngeal squamous cell carcinoma [6
]. However, use of the FAP PCR system allowed us to detect a broader spectrum of HPV types, particularly viruses that are more commonly isolated from cutaneous cancers and skin lesions [12
]. The different spectrum of HPV types detected in the oral cavity and cervicovaginal region provides an insight into a wider tissue distribution of β- and γ-HPV types than was previously recognized and supports the notion that the oral cavity consists of a complex biological niche [25
]. In addition to certain types of sexual behaviors that increase the risk of HPV infection, direct mouth-to-mouth and/or skin-to-mouth contact may be involved in the transmission of skin types to the oral cavity.
The high prevalence of oral HPV infection in HIV-positive patients is consistent with a number of studies demonstrating that HPV has a higher prevalence in the oral cavity of HIV-positive individuals compared with HIV-negative individuals [26
]. Moreover, the observation that the majority of HPV types detected in the oral rinse specimens from HIV-positive individuals was from the α-HPV genus supports the findings in these other reports. Nevertheless, there was also an abundance of β- and γ-HPV types detected in these samples that have not been widely recognized.
This study demonstrates the broad spectrum of HPV types detected within the oral cavity, although the pathological consequence of these infections requires further investigation. The fact that HPV types associated with skin cancer (eg, HPV-5 and HPV-8) were detected raises the question of whether there is another spectrum of oral or oropharyngeal tumors related to β- and γ-HPV type infections. Moreover, these results have significant implications for understanding the biology of HPV and the epidemiological association of HPV with oral and skin neoplasia. One possibility is that different variants of a given type infect predominantly the skin or the oral cavity. This would imply a relatively recent adaptation of a large number of HPV types to the oral cavity, given the well-established tropism of the β- and γ-HPV types for the skin. Alternatively, it is possible that the preferred site of infection for β- and γ-HPV types might be the oral cavity, and the skin could represent a satellite site of infection arising from hand-to-mouth transmission. Finally, serologic assays used to evaluate total body β- and γ-HPV type prevalence in association with skin cancer risk need to consider the role of oral HPV colonization.
This study has limitations. This analysis was conceived as a molecular virology investigation to identify a very broad spectrum of HPV types in samples from the oral cavity and was not meant to be a direct comparison between populations or samples. Thus, we are not able to compare risk factors for the different genera of HPV types detected in the oral cavity between populations, nor are these populations meant to be representative of a general HIV-negative or HIV-positive population. Therefore, we have not performed statistical analyses between populations. We contrast HPV types detected in oral rinse samples and cervical samples, since we used the same methods at the same time. Nevertheless, the identification of large numbers of oral samples from 2 different populations containing β- and γ-HPV types, many of which are novel, provides a new observation to be followed up in well-designed epidemiological studies.