Post-treatment clinical surveillance for HPV-associated oropharyngeal cancer.

Presentation: AHNS-027
Topic: Mucosal - HPV Positive
Type: Oral
Date: Wednesday, May 1, 2019
Session: 4:05 PM - 5:00 PM Scientific Session 4 - HPV Positive
Authors: Farzad Masroor, MD1, Nicholas Cheung, BS2, David Corpman, BS3, Diane Carpenter, MPH4, Kevin H Wang, MD1
Institution(s): 1Kaiser Permanente Oakland Medical Center, 2University of Southern California Keck School of Medicine, 3University of California San Francisco School of Medicine, 4Kaiser Permanente Northern California Division of Research

Background: National Comprehensive Cancer Network (NCCN) guidelines recommend routine clinical follow-up as part of post-treatment surveillance for head and neck cancer (HNC) patients.  Human papilloma virus-associated oropharyngeal cancer (HPV+OPC) is a unique subset of HNC, associated with less recurrence and improved survival. We sought to determine the utility of clinical surveillance for this cohort.

Methods: In this retrospective study of patients with HPV+OPC diagnosed between 2011–2014 at a large integrated healthcare system, we assessed whether adherence to NCCN guidelines and method of recurrence detection were associated with improved survival. Bivariate analyses were done with the Kaplan-Meier estimator and log-rank test; multivariable analyses were conducted using the Cox proportional hazards model, with patient adherence to NCCN visit guidelines as a time-dependent variable. 

Results: Median follow-up time was 4.5 years (IQR: 3.8–5.6).  Subjects demonstrated 83.0%, 52.7%, 73.4%, 62.3%, and 52.9% adherence to NCCN surveillance guidelines in years 1 through 5, respectively.  A total of 3,358 clinical surveillance examinations were performed to detect recurrences in 10 symptomatic patients (4 with local/regional and 7 with distant recurrences) and 1 asymptomatic patient with a regional recurrence. Of the clinically detected recurrences, salvage was attempted in 6 patients (3 local resections, 2 neck dissections, and 1 metastatectomy). At the study end date, 1 was alive, 4 deceased, and 1 lost to follow-up. Surveillance imaging detected 11 additional recurrences. All locoregional recurrences occurred within the first 2 years, and all salvageable recurrences occurred within the first year. No second primary cancers of the head and neck were identified.  Of the total 22 patients having recurrence, 19 (86.4%) adhered to NCCN guidelines in the interval prior to diagnosis.  Among patients having recurrence there was no survival advantage on Kaplan-Maier estimation with method of recurrence detection (p=0.300), adherence to NCCN guidelines (p=0.554), nor to being seen early for recurrence detection (p=0.609). Adherence to NCCN guidelines in the interval prior to recurrence diagnosis was not associated with mortality in the multivariable Cox model (referent: no adherence, HR 0.78, 95% CI 0.20–3.01).  Of patients having recurrence, 16 (72.7%) died by the end of follow-up; median survival time after recurrence diagnosis was 2.6 years (IQR 1.7-3.9).

Conclusion: For HPV+OPC patients, clinical surveillance is exceptionally low yield. Nearly all clinically-detected recurrences were elicited by patient symptoms that prompted earlier presentation to the clinician.  Adherence to the current schedule does not confer survival advantage and recurrences are almost never detected beyond two years. Our study provides support for a previously proposed de-escalated clinical surveillance schedule of every three months for the first six months, every six months until two years, and then annually thereafter.