Human papillomavirus (HPV) has been implicated as a possible etiological factor in the development of squamous-cell carcinoma of the esophagus. Published data demonstrating HPV DNA in these lesions have been conflicting, varying between failure to detect HPV DNA to detection of up to 60% to 70% of the biopsies harboring HPV DNA, mainly HPV 16 and HPV 18. We have analyzed esophageal carcinoma samples from 2 high-risk areas, China and South Africa, using a degenerate PCR approach. All amplified products were cloned and sequenced. A broad spectrum of HPV types was demonstrated in 10/29 samples from China and 9/34 samples from South Africa. HPV types detected included mucosal types HPV 6, 18, 51, 52 and 57; cutaneous types HPV 9, 20, 24 and 25; and the putative new HPV types DL231, DL428 and DL436, with HPV 6/51, 6/57, 20/9 and 20/DL231 occurring as double infections. HPV 6 predominated (4 samples) in 11 esophageal papillomas originating from patients in Europe and tested for HPV DNA. Other HPV types present included HPV 20, DL284 and DL436. Another putative new HPV type, DL416, was identified in a dysplastic lesion of the esophagus.