Prognostic Implication of SOX2 Expression Associated with p16 in Oropharyngeal Cancer: A Study of Consecutive Tissue Microarrays and TCGA

Simple Summary The role of human papillomavirus (HPV) in oropharyngeal cancer (OPSCC) as a cause agent has been reported in much of the literature. As a surrogate marker, p16 immunohistochemical staining is used as the standard for classifying OPSCC, and the prognosis of p16+ OPSCC has been reported to be better than p16- OPSCC. However, it was necessary to study what is the next biomarker that could predict the prognosis after classification by p16. We assumed that SOX2 may be a potential biomarker. For each p16+ and p16- OPSCC, SOX2 was used to analyze whether the degree of expression level differed in survival and recurrence rates. The results showed that both immunohistochemical staining and mRNA expression level of SOX2 significantly affected the survival and recurrence rates of p16+ OPSCC patients in two different datasets which were constructed in differently ways. Our study presented the clinical applicability of SOX2 as a biomarker. For oropharyngeal squamous cell carcinoma (OPSCC), there are not enough additional robust biomarkers for subgrouping after the distinct classification using p16. As SOX2 is an emerging biomarker for cancer treatment, its clinical implication in OPSCC was evaluated using a consecutive tissue microarray (TMA) cohort consisting of 111 patients who underwent surgery as an initial treatment from May 2002 to December 2016 and 79 patients in The Cancer Genome Atlas (TCGA) dataset. In both datasets, p16+/SOX2(High) (HPV+/SOX2(High) in TCGA) showed the best prognosis among the four groups classified by SOX2 and p16 for 5-year overall survival (OS) and recurrence (all p < 0.05), but SOX2 did not make a significant difference in the prognosis of the p16- group. In the TMA cohort, SOX2(High) was significantly correlated with response to radiotherapy and lower pathologic T classification in the p16+ group (p = 0.001). In TCGA, correlations between SOX2 and tumor stage classification or radiotherapy were not observed; however, HPV+/SOX2(High) had a significantly low tumor mutation burden among the four groups (all p < 0.05). In summary, SOX2 was proven to be a potential marker to predict overall survival and recurrence in p16+ OPSCC. However, the role of SOX2 has not yet been confirmed in p16- OPSCC patients.