Prevalence of human papillomavirus in the oral cavity of an indigenous community from Southwest México

Highlights

• Prevalence of HPV infection in the oral cavity of a Mexican indigenous community

• Predominant genotypes were associated with benign pathologies.

• High-risk genotype variants derived from different lineages.

Abstract

Human papilloma virus (HPV) is a DNA virus associated with the development of cervical, penile, anal, vulvar, and oral cancers. In recent years, there has been an increase in oral cancer, which could be due to changes in sexual behavior in the general population. In México, there is scarce information on this regard, which prompted us to study HPV infection prevalence in the oral cavity of an indigenous community from the municipality of Siltepec, Chiapas, Mexico. Oral samples from 198 individuals were obtained with cytobrush for virus detection by nested PCR, using MY09/MY11 and GP5+/GP6+ primers, and positive samples were sequenced for HPV genotyping. We observed 12.1% HPV infection prevalence, which depended on gender, number of sexual partners, lack of using condoms, and oral sex practices. In contrast, no significant association between HPV infection and tobacco or alcohol consumption was detected. Furthermore, sequencing analyzes were performed where HPV-13 (21/24), -16 (2/24), -32 (1/24), -81 (1/24), and -83 (1/24) were evidenced and HPV-16 European/Asian and Asian/American E6 variants identified. These results demonstrated an important prevalence of HPV infection in the oral cavity of a Mexican indigenous community, where the predominant genotypes were associated with benign pathologies, and showed that high-risk genotype variants derived from different lineages.

Introduction

Human papillomavirus (HPV) belongs to a family of small non-enveloped virus with an 8-kb circular double-stranded DNA genome (Bernard et al., 2010), which infects skin basal cells and mucosa squamous epithelium and has been associated with cervical cancer (CC), representing a major public health problem worldwide. In developing countries, CC is the most frequent female cancer, as well as the main cause of cancer-related death (Bruni et al., 2015; Luna-Aguirre et al., 2018). In Mexico, CC ranked second in incidence (16.9%) and mortality (11.9%) after breast cancer in 2012, among malignancies occurring in the female population. There are nearly 200 types of HPV, of which approximately 50 infect the genital area (Alemany et al., 2015); mucosal HPV is classified as high and low risk depending on its association with neoplasia development. In addition to CC, about 30% to 40% of HPV-positive cases have been related to oral, oropharyngeal, penis, and vulva cancer (Muñoz et al., 2006). In this regard, prevalence of high-risk HPV-16 and -18 in oral and oropharyngeal cancer has been reported (Pytynia et al., 2014). Furthermore, HPV-16 was shown to be more frequent (>75%) and HPV-18 less frequent (<10%) in HPV-positive vulvar, vaginal, and anal carcinomas, as compared with CC (De Vuyst et al., 2009).

During the past two decades, numerous studies have associated HPV infection with other epithelial neoplasias, such as head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC; HNSCC subtype), which constitutes 3% and 2% of all malignant neoplasms in males and females, respectively (D'Souza and Dempsey, 2011). Some evidence has linked them to orogenital contact with the transmission of papillomavirus from the genital zone to the oral cavity. However, acquisition could be through mouth-to-mouth contact, autoinoculation, or independent events (Vigneswaran and Williams, 2014).

In recent decades, oropharynx cancer etiology has been associated with oncogenic HPV. In the United States the percentage of HPV positive-related oropharyngeal SCC and oropharyngeal tumors increased up to 82%; in Sweden, such an association increased up to 79% of tonsil SCC (Candotto et al., 2017). Recently, it was reported HPV-attributable fractions for the different HN subsites; HPV-attributable cancers amounted to 38,000 cases, whose relative HPV-16/-18 and HPV-6/-11/-16/-18/-31/-33/-45/-52/-58 contributions were 73% and 90%, respectively (Lobene, 1986).

In Mexico, there are few reports on the role of HPV infection in the oral cavity and it is very important to document the types and/or s HPV variants in different geographical regions. Provided that HPV promotes cervical, oral, and anal carcinogenesis, there is evidence that all these tumors can be preventable either with an efficient early diagnosis by detecting premalignant lesions, such as low and high grade intraepithelial lesions, accompanied by HPV detection or by broad HPV vaccination coverage to the population (women and men) (Schiffman, 2007). Because of recent changes in sexual behavior in the general population (for example, early initiation of sexual activity, increase in the number of sexual partners, and orogenital sexual practices), exposure to oral and genital infection occurs at early ages (Candotto et al., 2017).

It is important to determine HPV prevalence in the oral cavity of healthy people, and individuals with pre-neoplasic lesions or oropharyngeal carcinoma, to define prophylactic strategies. In particular, HPV detection and genotyping in the oral cavity would provide a better understanding of its prevalence and diversity in the Mexican population, especially from the municipality of Siltepec in Chiapas, Mexico.