Investigation of viral etiology in potentially malignant disorders and oral squamous cell carcinomas in non-smoking, non-drinking patients

Abstract

Head and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75-80% of cases. In addition to these risk factors, Human papillomavirus (HPV) types 16 and 18, classified as high-risk (HR) HPV genotypes, are considered as risk factors for oropharyngeal cancers, but their role in the development of OSCC remains unclear. We tested the hypothesis of viral etiology in a series of 68 well-characterized OSCCs and 14 potentially malignant disorders (PMD) in non-smoking, non-drinking (NSND) patients using broad-range, sensitive molecular methodologies. Deep-sequencing of the transcriptome did not reveal any vertebrate virus sequences other than HPV transcripts, detected in only one case. In contrast, HPV DNA was detected in 41.2% (28/68) and 35.7% (5/14) of OSCC and PMD cases, respectively. Importantly, 90.9% (30/33) of these belonged to the Betapapillomavirus genus, but no viral transcripts were detected. Finally, high-throughput sequencing revealed reads corresponding to transcripts of the Trichomonas vaginalis virus (TVV), which were confirmed by RT-PCR in two OSCCs. Our results strongly suggest that Alphapapillomavirus genotypes classified as HR are not involved in the development of OSCCs in NSND patients and that known oncogenic infectious agents are absent in these specific OSCCs. Any possible direct or indirect role of Betapapillomavirus genus members and TVV in OSCCs remains speculative and requires further investigation.

Molecular drivers of oral cavity squamous cell carcinoma in non-smoking and non-drinking patients: what do we know so far?

“… 66 Theoretically, such changes could persist after clearance of the virus. While another study detected no significant viral RNA transcripts in a set of 68 oral cancers from NSND patients, 67 this may be a fruitful avenue for investigation into mechanisms of OCSCC in NSND populations.…”

“Fact or fiction?”: Oral cavity cancer in nonsmoking, nonalcohol drinking patients as a distinct entity—Scoping review

“…Also, Pérot et al 26 detected only HPV transcripts in one NSND case and no other oncogenic viruses in others following RNA sequencing. This study further speculated on the role of ß‐papillomaviruses and Trichomonas vaginalis virus in oral carcinogenesis which remains to be investigated 26 …”

“…This study further speculated on the role of ß-papillomaviruses and Trichomonas vaginalis virus in oral carcinogenesis which remains to be investigated. 26 Inherent cancer susceptibility among NSND patients was also investigated. Familial cancer was used as a surrogate measure of genetic predisposition and a report found that NSND patients with familial cancer history had higher odds than healthy nonsmokers and drinkers to develop OCSCC.…”

Association of salivary Cathepsin B in different histological grades among patients presenting with oral squamous cell carcinoma

“…Oral squamous cell carcinoma (OSCC) is the most common and frequent type of oral cancer which accounts for approximately 90% of all oral cancers [4,5]. Annual incidence rate of oral cancer is 300,000 cases and mortality rate is 145,000 cases worldwide approximately [6]. Most common sites of OSCC occurrence are buccal mucosa, tongue and floor of the mouth [7].…”