Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China - A study of 700 cases by screening and type-specific in situ hybridization

Background: Human papillomavirus (HPV) DNA has been identified in esophagea l precancerous lesions and carcinomas. However, there are marked variations in the prevalence of HPV infection reported in different studies. Most pre vious studies on HPV and esophageal carcinomas have been based on a limited number of biopsy samples studied by different HPV detection methods with h ighly variable sensitivity and specificy, making systematic studies of larg er series clearly warranted. Methods: A series of 1876 surgical specimens ( primary tumor, adjacent epithelium, regional lymph nodes, resection margins ) from 700 patients surgically resected for an invasive squamous cell carci noma of the esophagus in the high- incidence area of China was analyzed for the presence of HPV DNA with screening in situ hybridization (ISH) using b iotinylated HPV DNA probes and followed by type-specific ISH for HPV 6, 11, 16, 18, 30, and 53. Results: Of the 700 esophageal carcinomas, 118 (16.9%) were shown to contain HPV DNA sequences by screening ISH. Positive signals were most frequent in the cancer cells (16.6%), more rare in the surroundi ng hyperplastic and dysplastic epithelia (5.6%), and infrequently present i n the resection margins (0.2%). HPV signals were also detected in cancer ce lls in 6.9% of the lymph node metastases. HPV types 6, 11, 16, 18, and 30 a ccount for 39.8% of the HPV-positive lesions, of which the high-risk types HPV 16 and 18 were present in 27.1% (32 of 118). Notably, 60.2% of the HPV- positive lesions contained DNA sequences other than HPV types 6, 11, 16, 18 , 30, and 53. Conclusions: This study reports the largest series of esophag eal cancers ever analyzed for the presence of HPV DNA. Our results confirm the presence of common mucosal HPV types in esophageal carcinomas but also suggest the involvement of other (novel?) HPV types that are unusually dete cted in genital cancers in a significant proportion of these lesions. The r esults further indicate that HVP has an etiologic role in esophageal carcin ogenesis, at least in the high-incidence area of northern China.