Transcriptionally Active High-Risk HPV: Uncommon in Oral Squamous Carcinomas
Qian Dai, Jie Xu, Tatyana Isayeva, Dayan Dan, George Jour, Marilena Vered, Bruce Wenig, Margaret Brandwein-Gensler. UAB, Birmingham, AL; Tel-Aviv University, Tel-Aviv, Israel; Continuum Health Partners Beth Israel Medical Center, New York, NY
Background: Transcriptionally active high-risk Human Papillomavirus (HR-HPV) is important in promoting many oropharyngeal carcinomas (OPC). HR-HPV-mediated OPC are associated with significantly improved outcomes, forming the basis for new treatment paradigms. Few large-scale studies have looked at HR-HPV genome detection rate in oral squamous carcinoma (OSC) by PCR. No prior study has examined the transcriptional activity of HPV in OSC; this speaks to the issue of biologically relevant, versus bystander infection. Here, we look for the presence of transcriptionally active HR-HPV in 87 patients with OSC.
Design: RNA was extracted from archival OSC resections from three academic centers. Reverse transcription, and nested real-time PCR (RT-PCR) were performed with separate primers to HPV16 E6 (including E6*)/E7 and HPV18 E6/E7. Tumors were categorized as positive if both E6 and E7 transcripts were detected. Positive controls (SiHa, HeLa, archival HPV16+ oropharyngeal SCC) and negative controls (HeLa, pancreatic carcinoma, and no tissue) were included in all reactions, which were run in duplicate. Tumors were classified as HPV+ only if both concordant E6 and E7 transcripts were present. Data on demographics (age, gender, stage, treatment, alcohol (Yes/No), smoking exposure (Yes/No)) and outcome (disease-progression, disease-specific survival) were collected. Fisher's exact test was used to analyze HPV status and demographics; Kaplan Meier curves were to analyze HPV status and outcome.
Results: This cohort consisted of 49 males (56%) and 38 females (44%) with a mean age of 61.3±12.8 years (range, 27-89). Alcohol and smoking exposures were present in 19/58 (33%) and 39/68 (57%)of patients, respectively. HPV16 transcripts were detected in 16/87 (18.4%) of OSC. There were no significant correlations with HPV16 status and patient age, gender, alcohol, or smoking exposure. There were no differences in time to disease-progression or disease-specific survival based on HPV16 status. HPV18 transcripts were detected in 12/47 (25.5%) of OSC. HPV18 studies are ongoing.
Conclusions: Transcriptionally active HPV16/18 infections are uncommon in OSC. There is no evidence to suggest that transcriptionally active HPV16 infection confers a large survival advantage for oral cancer patients, as has been demonstrated in the oropharynx. However, this study is not powered to observe smaller differences in outcome based on HPV status, neccesitating further study.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 167, Wednesday Morning