Objectives: Though HPV-related oropharyngeal squamous cell carcinomas (OPSCCs) show quite favorable prognoses, the exposure to carcinogen, such as tobacco canceled out the advantage of improved survival associated with HPV positivity. We have already reported that OPSCCs which demonstrate p16 positive and p53 negative in immunohistochemical (IHC) staining had much better prognoses in terms of overall survival (OS) and disease-specific survival (DSS) because this category of OPSCCs is supposed to represent HPV-related and carcinogen-unrelated OPSCCs. Herein, we present the advantage of this category of OPSCCs in survival, response rate to chemotherapy and multiple malignancy incidence and discuss about the possibility of de-intensive therapy to this category of OPSCCs.
Materials and Methods: This is a retrospective review of 100 consecutive cases with OPSCC between 2004 and 2016. Six cases without IHC staining were omitted and 94 cases were enrolled in this study. There were 45 cases with p16 positive/ p53 negative OPSCC (category1) and 49 cases with the other OPSCCs (category2). We compared the survivals and the incidences of synchronous/metachronous multiple malignancies between the categories. Thirty eight out of 94 patients who received the neoadjuvant chemotherapy (NAC) were enrolled in another investigation. The relationships between the categories and the response of NAC measured by RECIST, the change of accumulation of FDG (SUV) in PET/CT, and pathological findings were examined.
Results: The patients in category1 were significantly younger (category1:category2=60:67, mean) but no difference in gender. Main treatment modalities were similar in both categories (surgery: radiation=26:20 versus 23:23). Even though the patients in category1 consisted of more advanced stage than those in category2 (stage I-III: stage IV=14:31 versus 23:26), they showed significant better survivals in OS, DSS and recurrence free survival (RFS) (5-years OS: 89% versus 60% p=0.02, 5-years DSS: 94% versus 71% p=0.02, and 5-years RFS: 88% versus 41% p<0.01). The patients in category1 also demonstrated lower synchronous/metachronous multiple malignancy incidence rate (12% versus 38% p=002) in 5 years. The responses of NAC tended to be better in category1, when estimated using RECIST (RR=79% versus 63%), PET/CT (SUV diminishing rate >55% =81% versus 47%) and pathological findings (pathological CR rate =38% versus 27%).
Conclusions: The patients in category1 demonstrated excellent survival lower synchronous/metachronous multiple malignancy incidence and higher response rate to NAC. In the current treatment paradigm of OPSCC, chemo-radiation has a main role even for HPV-related OPSCCs, which leaves the survivor with significant and lifelong morbidity. Utilizing the high response to NAC, NAC with conservative surgery, such as transoral surgery with selective neck dissection could be a definitive treatment for p16 positive/p53 negative advanced OPSCCs.