L1 capsid protein expression in human papillomavirus positive Barrett's metaplasia-dysplasia-adenocarcinoma lesions.

Human papillomavirus (HPV) has been associated with a subset of Barrett's dysplasia and oesophageal adenocarcinoma (EAC). The HPV L1 capsid protein has been closely linked to disease regression and is a prognostic factor in HPV driven cancers of the cervix and anus. Thus, we investigated L1 protein expression in HPV-positive patients representing the esophageal squamous-Barrett's metaplasia-dysplasia-adenocarcinoma sequence. L1 protein immunohistochemical staining was correlated with p16 overexpression and E6/E7 mRNA in-situ-hybridization. Of 116 HPV DNA-positive patients [(age range: 19-90, mean (SD), 63.2 (13.5)], 88 males and 28 females), seventy-three (62.9%) were genotype 16, thirty-seven (31.9%) genotype 18 and six (5.2%) were genotype 6. L1 staining was identified in 64 individuals; 84.9% (28/33) controls; 94.1% (16/17) BE; 50% (7/14) LGD; (8/21) 38.1% HGD and 16.1% (5/31) EAC; [adjusted P < 0.0001]. Conversely, p16 was present in 9.1% (3/33) of controls, 17.7% (3/17) BE, 57.1% (8/14) LGD, 61.9% (13/21) HGD and 64.5% (20/31) of EAC subjects [p<0.0001]. Corresponding figures for E6/E7 mRNA positivity was 6.1% (2/33), 23.5% (4/17), 28.6% (4/14), 38.1% (8/21) and 45.2% (14/31) respectively [p=0.008]. Expression of HPV-L1 and p16 or L1 and E6/E7 mRNA was largely mutually exclusive. HPV L1 capsid expression is incrementally lost with increasing esophageal disease severity as in viral driven anal and cervical lesions. Utility of L1 alone or in combination with p16 and or E6/E7 mRNA in stratifying HPV-positive patients for treatment should be explored in a prospective longitudinal investigation.