Abstract
This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED (N = 19) and HNSCC (N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 (p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.
Highlights
Head and neck squamous cell carcinoma (HNSCC) originates from multiple anatomic sites, including the oral cavity and the oropharynx
This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia
This result indicated that both copies of HPV16 DNA in the SiHa cells were likely integrated into the chromosomal DNA via disrupted E2 sites, as reported previously [39]
Summary
Head and neck squamous cell carcinoma (HNSCC) originates from multiple anatomic sites, including the oral cavity (oral squamous cell carcinoma, OSCC) and the oropharynx (oropharyngeal squamous cell carcinoma, OPC). While HPV is strongly www.oncotarget.com associated with OPC, the relationship of HPV to OSCC and its premalignant precursor (high-grade oral epithelial dysplasia, hgOED) is not well understood. Our group [3] and others [4, 5] have recently reported that HRHPV is strongly associated with a certain histologic subset of hgOED, which is designated as HPV-associated oral epithelial dysplasia (HPV-OED). We concluded that cases of hgOED with greater cytologic change (group 3) are strongly associated with HPV, warranting the designation of HPV-OED. Because HPV16 was still identified in 42.3% of the lesions in groups 1 and 2, additional molecular study of these groups is needed to assess whether these differences determine the influence of HPV on the progression from dysplasia to malignancy
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