Larissa J Lee1, Brooke Howitt2, Paul Catalano3, Cynthia Tanaka4, Rita Murphy4, Nicole Cimbak4, Rebecca DeMaria4, Paula Bu4, Christopher Crum2, Neil Horowitz5, Ursula Matulonis6, Akila N Viswanathan7. 1. Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. Electronic address: llee@lroc.harvard.edu. 2. Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. 3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. 4. Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, United States. 5. Department of Gynecologic Oncology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. 6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. 7. Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Abstract
OBJECTIVE: HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). METHODS: Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58months among the 57 patients with an available tumor specimen. RESULTS: HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ=0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p<0.01) and OS (65% vs. 22%, p=0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p<0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status. CONCLUSION: In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting.
OBJECTIVE:HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). METHODS:Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58months among the 57 patients with an available tumor specimen. RESULTS:HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ=0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p<0.01) and OS (65% vs. 22%, p=0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p<0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status. CONCLUSION: In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting.
Authors: Michael T Spiotto; Cullen M Taniguchi; Ann H Klopp; Lauren E Colbert; Steven H Lin; Li Wang; Mitchell J Frederick; Abdullah A Osman; Curtis R Pickering; Steven J Frank Journal: Semin Radiat Oncol Date: 2021-10 Impact factor: 5.421