A retrospective analysis of oropharyngeal patients with recurrence of disease after primary therapy in the Radiation Therapy Oncology Group (RTOG) studies 0129 or 0522 found that HPV-positive patients had a higher overall survival (OS) rate than HPV-negative patients (at two years post-treatment, 54.6 percent vs. 27.6 percent, respectively), according to research presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
The analysis included 181 patients with stage III-IV oropharyngeal squamous cell carcinoma (OPSCC) with known HPV status (HPV-positive = 105; HPV-negative = 76), and cancer progression that was local, regional and/or distant after completion of primary cisplatin-based chemotherapy and radiation therapy (standard vs. accelerated fractionation (AFX)) in RTOG 0129 or cisplatin-AFX with or without cetuximab in RTOG 0522. Tumor status was determined by a surrogate, p16 immunohistochemistry.
Median time to progression was virtually the same for HPV-positive and HPV-negative patients (8.2 months vs. 7.3 months, respectively). Increased risk of death in univariate analysis was associated with high tumor stage at diagnosis (T4 vs. T2-T3), fewer on-protocol cisplatin cycles (?1 vs. 2-3) and distant vs. local/regional recurrent (for all, hazard ratios (HRs) >2.0 and p<0.05). Risk of death after disease progression increased by 1 percent per cigarette pack-year at diagnosis. Rates were estimated by Kaplan-Meier method and compared by log-rank. HRs were estimated by Cox proportional hazards models and stratified by treatment protocol.
In addition, HPV-positive and HPV-negative patients who underwent surgery after cancer recurrence also experienced improved OS compared to those who did not undergo surgery. (The effect may have been more pronounced among HPV-positive than HPV-negative patients.) Recurrence is most commonly in the lungs for both groups of patients.
“Our findings demonstrate that HPV-positive OPSCC patients have significantly improved survival after progression of disease when compared with HPV-negative patients. Median survival after disease progression was strikingly longer for HPV-positive than HPV-negative patients,” said lead author Carole Fakhry, MD, MPH, assistant professor in the Department of Otolaryngology Head and Neck Surgery at Johns Hopkins Medicine in Baltimore. “These findings provide us with valuable knowledge to better counsel and treat patients.”
3: Human Papillomavirus (HPV) and Overall Survival (OS) After Progression of Oropharyngeal Squamous Cell Carcinoma (OPSCC)
C. Fakhry1, Q. Zhang2, P. Nguyen-Tân3, D. Rosenthal4, A. El-Naggar4, A. Garden4, D. Soulieres3, J. Harris2, Q. Le5, M. Gillison6, 1Johns Hopkins Medical Institutions, Baltimore, MD, 2Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA, 3CHUM Hospital Notre Dame, Montreal, QC, Canada, 4MD Anderson Cancer Center, Houston, TX, 5Stanford University Medical Center, Stanford, CA, 6Ohio State University Medical Center, Columbus, OH
Background: HPV-positive tumor status is a strong and independent predictor of reduced risk of cancer progression for patients with newly diagnosed local-regionally advanced OPSCC. Currently unknown is whether HPV tumor status remains associated with OS after cancer progression.
Methods and Materials: A retrospective analysis of the association between tumor HPV status and OS after cancer progression was performed among patients with stage III-IV OPSCC enrolled in RTOG 0129 or 0522. Eligible cases included patients with known HPV status and cancer progression that was local, regional and/or distant after completion of primary cisplatin-based chemoradiotherapy (standard vs. accelerated fractionation [AFX]) in RTOG0129 or cisplatin-AFX with vs. without cetuximab in RTOG0522. Tumor HPV status was determined by a surrogate, p16 immunohistochemistry. Primary endpoint was time from first recurrence to death or last follow-up. Rates were estimated by Kaplan-Meier method and compared by log-rank. Hazard ratios (HRs) were estimated by Cox proportional hazards models stratified by treatment protocol.
Results: 181 patients with HPV-positive (n=105) or HPV-negative (n=76) OPSCC were included in the analysis. Median time to progression did not differ by HPV tumor status (8.2 vs. 7.3 months, p=0.67). Median follow-up after progression among surviving patients was four years (range 0.04-8.97). In univariate analysis, patients with HPV-positive OPSCC had significantly improved OS when compared with HPV-negative patients (at 2 years: 54.6% vs. 27.6%, p<0.001). Additional factors associated with increased risk of death in univariate analysis included high tumor stage (T4 vs. T2-3) at diagnosis, fewer on-protocol cisplatin cycles (?1 vs. 2-3), and distant vs. local/regional recurrence (for all, HRs >2.0 and p<0.05). Risk of death after progression increased by 1% per cigarette pack-year at diagnosis (p=0.002). In contrast, HPV-positive tumor status (HR 0.49, 95%CI 0.34-0.70) and salvage surgery (HR 0.44, 95%CI 0.28-0.68) significantly reduced the risk of death. After adjustment for tumor stage, recurrence type (distant vs. local-regional) and cumulative tobacco exposure, risk of death was reduced by half for patients with HPV-positive tumors (HR 0.48, 95%CI 0.31-0.74) and those who underwent salvage surgery (HR 0.48, 95%CI 0.27-0.84).
Conclusions: Patients with HPV-positive OPSCC have improved OS after progression of disease relative to patients with HPV-negative OPSCC. Adverse prognostic factors include advanced tumor stage and high cumulative tobacco exposure at diagnosis and distant metastases. However, salvage surgery confers a significant improvement in prognosis.
Supported by National Cancer Institute grants U10 CA21661 and U10 CA37422 and Bristol-Myers Squibb.
Author Disclosure Block: C. Fakhry: None. Q. Zhang: None. P. Nguyen-Tân: None. D. Rosenthal: None. A. El-Naggar: None. A. Garden: None. D. Soulieres: None. J. Harris: None. Q. Le: None. M. Gillison: G. Consultant; Bristol Myers Squibb, GlaxoSmithKline.