Detection of mucosal and cutaneous human papillomaviruses in oesophagitis, squamous cell carcinoma and adenocarcinoma of the oesophagus

Background: Epidemiologic evidence points to a connection between viral infections by the human papillomavirus (HPV) and a subgroup of squamous cell carcinomas of the oropharynx. Still controversial is the association of HPV infection with oesophageal neoplasia. Objectives: To investigate the presence of mucosal as well as cutaneous HPVs in squamous cell carcinoma and adenocarcinoma of the oesophagus. Study design: HPV DNA has been searched by PCR and characterized by nucleotide sequence analysis in paraffin-embedded biopsies from Italian patients with oesophageal squamous cell carcinoma (n = 36), sarcomatoid cell carcinoma (n = 1), adenocarcinoma (n = 20) and oesophagitis lesions (n = 27). Results: A broad spectrum of HPVs, primarily cutaneous types was demonstrated in 27.8% (10/36) of squamous cell carcinomas with a significantly higher frequency in well (G1) and moderately (G2) differentiated grades (47.3%, 9/19) compared to poorly (G3) differentiated (5.9%, 1/17) squamous cell carcinoma (p = 0.008), and in 10% (2/20) of adenocarcinomas and in 29.6% (8/27) of oesophagitis. HPV types detected included mucosal types HPV 6 and 16, cutaneous types HPV 8, 15, 20 and 25; and the putative new HPV types X14, X15, DL473, PPHL1FR and CJ198. Conclusions: There is no evidence of any association between mucosal HPVs and oesophageal neoplasia. The cutaneous HPVs are detected at low frequency in adenocarcinoma and poorly differentiated squamous cell carcinoma, while they are frequently detected in oesophagitis and in well and moderately differentiated squamous cell carcinoma suggesting their tropism for keratinized tissue, although a significant association with such neoplasias cannot be drawn.