Int J Biol Sci 2020; 16(6):1035-1043. doi:10.7150/ijbs.40880

Review

Molecular mechanisms underlying increased radiosensitivity in human papillomavirus-associated oropharyngeal squamous cell carcinoma

Huanhuan Wang1*, Bin Wang1*, Jinlong Wei1, Lingbin Meng2, Qihe Zhang1,3, Chao Qu1, Ying Xin3✉, Xin Jiang1✉

1. Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China
2. Department of Internal Medicine, Florida Hospital, Orlando, FL 32803, USA
3. Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China
*Huanhuan Wang and Bin Wang contributed equally to this work

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Citation:
Wang H, Wang B, Wei J, Meng L, Zhang Q, Qu C, Xin Y, Jiang X. Molecular mechanisms underlying increased radiosensitivity in human papillomavirus-associated oropharyngeal squamous cell carcinoma. Int J Biol Sci 2020; 16(6):1035-1043. doi:10.7150/ijbs.40880. Available from http://www.ijbs.com/v16p1035.htm

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Abstract

Oropharyngeal squamous cell carcinoma (OPSCC) is an important type of head and neck squamous cell carcinoma (HNSCC). The traditional risk factors for OPSCC include carcinogen intake, smoking, alcohol consumption, and lifestyle. In recent years, cases of human papillomavirus (HPV)-related OPSCC have gradually increased. At present, HPV-related OPSCC in developed Western countries comprise up to 90% of all OPSCC cases, while in other developing countries, the proportion of HPV-related OPSCC cases is also gradually increasing. Compared with HPV-negative OPSCC, HPV-positive OPSCC patients have better overall survival rates and local control rates and this improved prognosis may be related to the increased radiosensitivity of HPV-positive tumors. Due to this more favorable prognosis, many downgraded treatment schemes are gradually emerging, including simple radiotherapy instead of concurrent radiotherapy or reduced radiotherapy dose. However, there is insufficient theoretical basis for such schemes. Some studies have shown that delayed repair of DNA damage after radiation, G2/M arrest, increased hypoxia, and decreased proliferation capacity are the main reasons for the increased radiosensitivity of HPV-positive tumor cells. In this review, we discuss the four principles of tumor cell damage caused by radiation, including repair, reoxygenation, redistribution, and regeneration in order to reveal the mechanism whereby HPV increases the radiosensitivity of tumor cells. An attempt was made to provide sufficient information to facilitate more individualized treatment for HPV-positive OPSCC patients, under the premise of good tumor control.

Keywords: oropharyngeal squamous cell carcinoma, human papillomavirus, radiosensitivity, repair, reoxygenation, redistribution, regeneration