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.
Highlights
In 2015, head and neck squamous cell carcinomas (HNSCC), i.e. cancers of the mouth, nose, throat, larynx and sinuses, affected more than 5.5 million people worldwide and caused more than 379,000 deaths [1]
The aim of this study was to test the hypothesis of a viral etiology due to a known viral agent such as Human papillomavirus (HPV) or another, unknown or unforeseen, agent associated with an oncogenic process in a series of well-characterized potentially malignant disorder (PMD) and oral squamous cell carcinoma (OSCC) in NSND patients using very broad and sensitive methodologies
The sex ratio (M:F) was 0.16 and 0.94 with an average age of 70 years (+/- 15 years) and 69 years (+/- 15 years) for PMDs and OSCCs, respectively (Table 1), with 86.7% of patients being over 50 years of age in this study
Summary
In 2015, head and neck squamous cell carcinomas (HNSCC), i.e. cancers of the mouth, nose, throat, larynx and sinuses, affected more than 5.5 million people worldwide and caused more than 379,000 deaths [1]. HNSCC is the seventh most frequent cancer and the ninth most frequent cause of death from cancer Among these cancers, oral squamous cell carcinomas (OSCCs) include cancers of the inner mucosa of the lips, the cheeks and vestibule, the mobile part of the tongue, gums, the floor of the mouth, the intermaxillary region as well as the hard and anterior surfaces of the soft palate, but exclude the oropharynx (i.e. tonsils, base of the tongue, the posterior surface of the soft palate and the walls of the oropharynx) [2]. A subset of OSCCs appears on pre-existing lesions with a predisposition for malignant transformation, called “potentially malignant disorders” (PMDs) [4] This group of oral lesions mainly includes leukoplakia, erythroplakia, lichen planus and some other relatively rare disorders. The presence of epithelial dysplasia is considered the most important indicator of malignant potential [5]
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