SCREENING FOR HUMAN PAPILLOMAVIRUS INFECTIONS IN ESOPHAGEAL SQUAMOUS-CELL CARCINOMAS BY IN-SITU HYBRIDIZATION

Background. Infections with specific types of human papillomavirus (HPV) have been closely linked with human squamous cell carcinomas, those of the anogenital tract in particular. Increasing number of reports also suggest that HPV infection could be a risk factor for esophageal cancer. However, most of the previous studies on HPV involvement in esophageal carcinomas have included only small numbers of biopsy specimens, thus necessitating additional studies based on extensive series of esophageal samples. Methods. A series of 776 biopsy specimens derived from 363 patients who had undergone esophagectomy for squamous cell carcinoma in the high-incidence area of China were analyzed for the presence of HPV DNA by screening and specific typing in situ hybridization with biotinylated HPV DNA probes. Results. Under low-stringency conditions, 85 (23.4%) tumors were demonstrated to contain HPV DNA. Positive signals were found on the nuclei of cancer cells in 71 (19.6%), in the surrounding epithelial cells with hyperplastic or dysplastic changes in 13 (3.6%), in the cancer cells and the surrounding epithelial cells in 10 (2.8%), and in the resected margins in 1 (0.3%). Thirty-four (40%) of the 85 HPV-positive tumors were shown to contain at least one type of HPV 6, 11, 16, 18, or 30 DNA sequences. HPV 16 was the type found most frequently, occurring in 18.8% of the 85 HPV-positive specimens. In addition to the primary tumors, HPV DNA sequences were found in 12.3% (7 of 57) of the lymph node metastases. Conclusion. The results confirm the previously reported HPV involvement in esophageal squamous cell lesions and implicate HPV as a potential etiologic agent in the multifactorial pathogenesis of esophageal carcinoma.