Staging HPV-Related Oropharyngeal Cancer: Validation of AJCC 8 in a Surgical Cohort

Presentation: AHNS025
Topic: Pharynx / Larynx Cancer
Type: Oral
Date: Wednesday, April 18, 2018
Session: 2:20 PM - 3:10 PM Larynx/Pharynx
Authors: Mathew Geltzeiler, MD1, William G Albergotti2, John Gleysteen, MD1, Marnie Bertolet2, Michael Persky, MD2, Neil D Gross, MD3, Ryan Li, MD1, Peter Andersen, MD1, Seungwon Kim, MD2, Robert L Ferris2, Umamaheswar Duvvuri2, Daniel Clayburgh, MD1
Institution(s): 1Oregon Health & Science University, 2University of Pittsburgh Medical Center, 3MD Anderson Cancer Center

Introduction: The American Joint Committee on Cancer (AJCC) recently released the 8th edition Cancer Staging Manual (AJCC-8) with modifications to the human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) staging system. The goal of our study was to apply AJCC-8 criteria to a multi-institutional cohort of surgically treated patients with HPV-related OPSCC.  Importantly, in this study we examined the prognostic capacity of AJCC-8 relative to both clinical and pathologic staging. 

Methods: A retrospective review of a prospectively collected multi-institutional dataset was performed.  All included patients had a diagnosis of HPV-related OPSCC as determined by p16 immunohistochemistry and were treated with surgery as a primary treatment modality.  Surgical approaches included open, direct transoral and transoral robotic surgery (TORS).  Adjuvant radiation and/or chemotherapy were given to patients per the treating teams. 

Each patient was staged both clinically and pathologically according to both AJCC-7 and AJCC-8 criteria. The primary outcome measure was overall survival. The Kaplan-Meier method was used to calculate cumulative probability of survival, and differences were evaluated with log-rank tests. Cox proportional hazard regression was used for a multivariable regression analysis.  Akaike’s Information Criteria (AIC) analysis was then used to compare the Cox analyses. 

Results:  Three hundred and nine patients were included in the study with surgical dates from March 1983 to December 2015.  Median follow up was 33 months (range 12-345).  The median age at diagnosis was 57 years (range of 30-80).  Sixty-four percent of the primary tumors were located in the base of tongue (BOT) while 33% were found in the tonsil. Seventy-four patients (24%) underwent surgery alone while one hundred two (33%) received adjuvant radiation therapy and 133 patients (43%) received adjuvant chemoradiation therapy.

The p-value for the log rank test for AJCC-7 clinical and pathologic were 0.085 and 0.873, respectively.  The long rank p-values for AJCC-8 clinical and pathologic were 0.0001 and <0.0001, respectively.  The AIC confirmed that in our surgical cohort, AJCC-8 pathologic staging is a statistically better staging system than AJCC-7 pathologic (p= <0.001).

When examining AJCC-8 alone, pathologic data did not change the clinical staging for 235 patients (76%) while 43 patients (14%) were upstaged by 1 stage, 1 patient (0.4%) was upstaged by 2.  Twenty-one patients (7%) were downstaged by 1 and 9 patients (1%) were downstaged by 2.  The AIC showed that the AJCC-8 pathologic criteria more accurately stratifies surgical patients than AJCC-8 clinical, but this difference is not statistically significant (p=0.56).

Conclusion: The updated AJCC 8 staging system is a significant improvement over the AJCC-7 for patients with HPV-related OPSCC treated surgically.  While the AJCC-8 pathologic criteria did perform better than the AJCC-8 clinical criteria, this difference was not statistically significant.    Since the treatments applied to this cohort after surgery were based on AJCC-7 staging, future decisions regarding adjuvant therapy for HPV-related OPSCC may require consideration of factors outside of AJCC-8 criteria.