Open AccessMutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status
Author(s) -
Reder Henrike,
Wagner Steffen,
Wuerdemann Nora,
Langer Christine,
Sandmann Sarah,
Braeuninger Andreas,
Dugas Martin,
Gattenloehner Stefan,
Wittekindt Claus,
Klussmann Jens Peter
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3741
Subject(s) - medicine , stk11 , oncology , hras , mutation , human papillomavirus , cancer , gene , cancer research , biology , kras , genetics , colorectal cancer
Abstract Patients with HPV‐driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV‐negative (HPV−) OPSCC. Nevertheless, 13%–25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV−OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV−OPSCCs, which is associated with severe outcome. We performed targeted next‐generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV−OPSCC of patients with/without LDR regarding protein‐altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV−OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP53 , HPV−OPSCC had significantly more protein‐altering mutations than HPV+OPSCC. The number of mutations was similar in HPV−OPSCC of patients with and without LDR with the exception of FAT1 , which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS , PIK3R1 , STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV−OPSCC, except TP53 , which was mutated to a significantly lower extent. In conclusion, HPV−and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important.