**7. HPV status and treatment response**

There are many factors attributed to the survival advantage for p16 positive oropharyngeal carcinoma. Many of the patients are younger, they have fewer comorbidities and less chance of field cancerization given reduced smoking history. HPV-positive tumours may harbour fewer or different genetic alterations. HPV-positive tumours have higher radio sensitivity, due to compromised DNA repair capacity [12]. Other studies have reported intrinsic radiation sensitivity and increased apoptosis following radiation exposure [13]. The immunologic response may play a role in the improved response to radiotherapy and chemotherapy in HPV-positive tumors.

The survival advantage noted for HPV positive OPSCC in the radiotherapy setting has been summarized in **Table 4**. Retrospective analysis of the HPV positive subgroup in the RTOG 0129 trial reported a strong association between HPV status and good survival [19]. They risk stratified the patients as having a low, intermediate, or high risk of death based on the combination of tumor HPV status, packyears of tobacco smoking, and cancer stage. In the low-risk group, which included


**Table 4.**

*Major randomized trials that have reported survival benefit for HPV positive subset.*

HPV positive and non-smokers, 3-year disease-free survival (DFS) was 93% when compared to<50% in the high-risk group which included the HPV negative and smokers. The intermediate-risk group included HPV positive patients with smoking history and HPV negative non -smokers. This led to the thought for de-intensification of the multimodality approach for low-risk category patients. In the post-op setting, the German radiation oncology group study showed a better correlation of HPV positive status with oropharyngeal carcinoma subsite and better outcomes in the patients undergoing adjuvant chemoradiation for locally advanced head and neck cancers [21]. Retrospective analysis of IMCL-9815 study, where patients were treated with radiotherapy with or without Cetuximab, the overall survival was better for p16 positive patients [22]. In the abovementioned trials, a better prognosis for HPV positive oropharyngeal carcinoma was independent of treatment modality. The association of HPV positive status with improved outcome was restricted to the oropharyngeal primary site [23].
