The molecular mechanisms of increased radiosensitivity of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC): an extensive review

Changxing Liu, Daljit Mann, Uttam K. Sinha, Niels C. Kokot

Head and neck carcinomas (HNCs) collectively are the sixth most common cancer with an annual incidence of about 400,000 cases in the US. The most well-established risk factors for HNCs are tobacco and alcohol abuse. With the increasing public awareness, the incidence of HNCs is decreasing. But there is an increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been observed during the last decade. This phenomena is associated with persistent infection with high-risk HPV. HPV associated OPSCC patients tend to be younger males of high socioeconomic status. The increasing incidence causes a significant loss to social resources, given that it's reported that HPV associated OPSCC represents about 60% of OPSCC cases. There is a growing amount of data supporting the hypothesis that HPV-associated OPSCC has a better survival rate due to a higher sensitivity to chemotherapy and radiotherapy as compared to HPV-unrelated OPSCC. Although the HPV positivity is associated with increased radio-sensitivity, the underlying mechanisms are not yet fully understood. This review summarizes the current knowledge on the effects of HPV infection and its carcinogenesis on the radiosensitivity of OPSCC, from the molecular to histologic level, providing a comprehensive insight of this special tumor entity.