Human Papillomavirus Oral Infection: Review of Methodological Aspects and Epidemiology

Abstract

Oral infection by Human Papillomavirus (HPV) has recently gained great attention because of its involvement in the development of a subset of head and neck squamous cell carcinoma. The role of specific Alpha-HPVs in this regard has been well established, whereas the contribution of other genera is under investigation. Despite their traditional classification as "cutaneous" types, Beta and Gamma HPVs are frequently detected in oral samples. Due to the lack of a standardized protocol, a large variety of methodologies have been used for oral sample collection, DNA extraction, HPV detection and genotyping. Laboratory procedures influence the evaluation of oral HPV prevalence, which largely varies also according to the population characteristics, e.g., age, gender, sexual behavior, Human Immunodeficiency Virus (HIV) status. Nevertheless, oral infection by Beta and Gamma HPVs seems to be even more common than Alpha-HPVs. The latter is 5-7% in the general population, and increases up to 30% approximately in HIV-infected men who have sex with men. Despite major advances in the evaluation of oral HPV prevalence, its natural history is still little understood, especially for Beta and Gamma HPVs. The latest technologies, such as Next Generation Sequencing (NGS), can be exploited to gain new insights into oral HPV, and to improve the identification of novel HPV types.

Keywords: Alphapapillomavirus; Betapapillomavirus; Gammapapillomavirus; Human Papillomavirus; clearance; detection method; incidence; oral infection; oropharyngeal infection; prevalence.

Figure 1

Laboratory workflow for the assessment of oral HPV infection. The operating laboratory procedures are represented in sequence: the oral sample collection (followed by sample processing), DNA extraction and purification, HPV-DNA amplification, detection and typing. Numerous HPV testing methods are available but only the methodologies mentioned in the text are depicted.

Figure 2

Overview of the oral cavity and oropharynx anatomy. The regions included in the two head and neck subsites that may be targeted by HPV are shown.

Figure 3

The main factors influencing the estimation of oral HPV infection. The assessment of oral HPV infection (in terms of prevalence, incidence and clearance) may be largely influenced by methods used for oral sample collection, DNA extraction, HPV-DNA amplification, detection and typing as well as by demographical, behavioral and clinical factors.