Extracapsular extension of neck nodes and absence of human papillomavirus 16-DNA are predictors of impaired survival in p16-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV-negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV-driven disease. In p16-negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16-positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16-positive OPSCC. In a cohort of 92 patients with p16-positive, lymph node (N)-positive (stage III-IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16-positive/HPV16 DNA-positive, 62 of 92 (67%) were ECE-positive, and 45 of 62 (72.6%) were ECE-positive, p16-positive, and HPV16 DNA-positive. Differences in outcome were assessed using Kaplan-Meier plots and Cox proportional hazard regression (CoxR) for tumor-specific survival and overall survival (OS). The mean numbers of positive lymph nodes in ECE-positive patients (5.0 positive lymph nodes; 95% CI, 3.8-6.4 positive lymph nodes) and ECE-negative patients (2.4 positive lymph nodes; 95% CI, 1.8-2.9 positive lymph nodes) were different (P = .0007). ECE affected OS and tumor-specific survival in p16-positive patients (P = .007 and P = .047, respectively) and in p16-positive/HPV16 DNA-positive patients (P = .013 and P = .026, respectively). Related to the unequal distributions of ECE-positive/HPV16 DNA-negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16-positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17-9.89; P = .025) and even greater impaired OS in those with p16-positive/HPV16 DNA-positive OPSCC (HR, 8.64; 95% CI, 1.12-66.40; P = .038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16-positive OPSCC because several lines of evidence demonstrate their impact on survival.

Freitag J ，Wald T ，Kuhnt T ，Gradistanac T ，Kolb M ，Dietz A ，Wiegand S ，Wichmann G ... -  《-》

Confirmation of the eighth edition of the AJCC/UICC TNM staging system for HPV-mediated oropharyngeal cancer in Japan.

Mizumachi T ，Homma A ，Sakashita T ，Kano S ，Hatakeyama H ，Fukuda S ... -  《-》

Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing.

Nauta IH ，Rietbergen MM ，van Bokhoven AAJD ，Bloemena E ，Lissenberg-Witte BI ，Heideman DAM ，Baatenburg de Jong RJ ，Brakenhoff RH ，Leemans CR ... -  《-》

The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer.

Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs). This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS). The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS. For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society.

Fakhry C ，Westra WH ，Wang SJ ，van Zante A ，Zhang Y ，Rettig E ，Yin LX ，Ryan WR ，Ha PK ，Wentz A ，Koch W ，Richmon JD ，Eisele DW ，D'Souza G ... -  《-》

PET/CT Poorly Predicts AJCC 8th Edition Pathologic Staging in HPV-Related Oropharyngeal Cancer.

The American Joint Committee on Cancer (AJCC) 8th edition introduced distinct clinical and pathological staging paradigms for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Treatment planning for OPSCC often utilizes positron emission tomography/computed tomography (PET/CT) to assess clinical stage. We hypothesize that PET/CT will accurately predict final pathologic AJCC 8th edition staging in patients with HPV+ OPSCC. All patients with primary HPV+ OPSCC with preoperative PET/CT who underwent transoral robotic surgery and neck dissection between 2011 and 2017 were identified. Data were collected via chart review. Two neuroradiologists performed blinded re-evaluation of all scans. Primary tumor size and cervical nodal disease characteristics were recorded and TNM staging was extrapolated. Cohen's kappa statistic was used to assess interrater reliability. Test for symmetry was performed to analyze discordance between radiologic and pathologic staging. Forty-nine patients met inclusion criteria. Interrater reliability was substantial between radiologists for nodal (N) and overall staging (OS) (κ = 0.715 and 0.715). Radiologist A review resulted in identical OS for 67% of patients, overstaging for 31%, and understaging for 2%. Radiologist B review resulted in 61% identical OS, 39% overstaging, and 0% understaging. In misclassified cases, the test of symmetry shows strong bias toward overstaging N stage and OS (P < .001). Radiologic interpretation of extracapsular extension showed poor interrater reliability (κ = 0.403) and poor accuracy. PET/CT predicts a higher nodal and overall stage than pathologic staging. PET/CT should not be relied upon for initial tumor staging, as increased FDG uptake is not specific for nodal metastases. PET/CT is shown to be a poor predictor of ECE. 4 Laryngoscope, 131:1535-1541, 2021.

Snyder V ，Goyal LK ，Bowers EMR ，Kubik M ，Kim S ，Ferris RL ，Johnson JT ，Duvvuri U ，Gooding WE ，Branstetter BF ，Rath TJ ，Sridharan SS ... -  《-》