African Americans with Oropharyngeal Carcinoma: Decreased Transcriptionally Active High-Risk Human Papillomavirus Contributes to Poorer Survival
Jie Xu, Qian Dai, Tatyana Isayeva, Shantel Hebert-Magee, Margaret Brandwein-Gensler. University of Alabama at Birmingham, Birmingham, AL
Background: High-risk Human Papillomavirus (HPV), mostly HPV16 (90%), followed by HPV18 (5%), promote at least 50% of oropharyngeal cancers (OPC). Recent studies confirm the improved outcome for HPV+ OPC patients, compared to HPV- counterparts. Settle et al recently demonstrated a significantly poorer survival for African Americans (AA) with OPC, as compared to Caucasians; they attributed this to differences in HPV infection rates. However their study assessed only HPV DNA, rather than confirmed the viral transcriptional status.
Design: We retrospectively identified 102 consecutive patients with OPC. Data on demographics (age, gender, race, stage, treatment, alcohol (Yes/No), smoking exposure (Yes/No) and outcome (progression-free survival (PFS), disease-specific survival (DSS)) were collected. RNA was extracted from archival tissue blocks of interest and reverse transcription was performed. Nested quantitative real-time PCR was performed with primers to HPV16 (E6 (including E6*)/E7 and HPV18 (E6/E7). Positive and negative controls (SiHa, HeLa, HPV16+ OPC, and pancreatic carcinoma, water, respectively) were included in all reactions. Tumors were classified as HPV+ if both concordant E6 and E7 transcripts were present. The data were analyzed by two-tailed Fisher's exact test and Kaplan Meier (KM) curves.
Results: This cohort of 102 patients included 78 Caucasians and 24 African Americans (AA) with OPC. Among Caucasians: 54% (42/78) were HPV16+, 12% (9/78) were HPV18+, and 6% (5/78) were double positive. Among AA: 29% (7/24) were HPV16+, 17% (4/24) were HPV18+, and none were double positive. OPC from Caucasians were significantly associated with HPV16 (p = 0.039). KM curves revealed decreased time to PFS and DSS for AA patients (p = 0.007, and p = 0.001, respectively) compared to Caucasians. Improved PFS and DSS was associated with HPV16+ OPC (all races, p = 0.007, and p = 0.006, respectively). No associations were seen for HPV18. Figure 1 demonstrates disease-specific survival per race and HPV16 status (p = 0.0010).
Conclusions: Our data confirm that transcriptionally active HPV16 imparts an improved prognosis for Caucasians with OPC. OPC in AA patients are significantly less likely to be HPV16-mediated.
Category: Head & Neck
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 198, Monday Morning