Simultaneous in situ genotyping and phenotyping of human papillomavirus cervical lesions:comparative sensitivity and specificity

The sensitivity and specificity of immunocytochemistry were compared with those of non-isotopic in situ hybridisation (NISH) for the direct detection of human papillomaviruses in biopsy specimens. Four monoclonal antibodies raised to the capsid protein of HPV16 were less specific than NISH: all four reacted with lesions containing HPV33, and HPV18. Absolute discrimination of HPV types, therefore, was not possible with the monoclonal antibodies used in this study. The relative sensitivities of these antibodies were also lower than NISH. Sequential immunocytochemistry and NISH on the same section showed that 2.9-13.0 times as many cells were positive by NISH than by immunocytochemistry using the most sensitive monoclonal antibody. These data indicate that NISH has higher diagnostic specificity and sensitivity than immunocytochemistry using monoclonal antibodies to the HPV16 capsid protein

Recent striking changes in histological differentiation and rate of human papillomavirus infection in squamous cell carcinoma of the lung in Okinawa, a subtropical island in southern Japan

Aims—The incidence of lung cancer in Okinawa has been the highest in Japan since 1975, and squamous cell carcinoma (SCC), especially the well differentiated form, is the most prevalent form in Okinawa, although well differentiated SCC is relatively rare in mainland Japan. Furthermore, a high proportion of SCC of the lung in Okinawa was positive for human papillomavirus (HPV). In this study, we report recent striking changes in histological features and in the incidence of HPV infection. Methods—In Okinawa between 1986 and 1998, 1109 surgically resected lung tumours were examined histopathologically. In addition, human papillomavirus infection was detected by the polymerase chain reaction and Southern blot analysis in SCC cases reported in 1993 and 1995–8. Non-isotopic in situ hybridisation of HPV DNA was also carried out. Results—Up until 1994 SCC, especially the well differentiated form, was the most prevalent type of tumour. However, since 1995 the number of such cases has diminished steadily, accompanied by a slight rise in the incidence of adenocarcinoma. Although most present and past patients are heavy smokers, the incidence of SCC, especially the well differentiated form, continues to decrease steadily. Furthermore, in 1993, HPV was detected in 79% of all cases, and was particularly prevalent in the well differentiated form, but the rate fell to 68% in 1995, 35% in 1996, 23% in 1997, and 24% in 1998. The age distribution of patients, the male to female ratio, and the number of tumours overexpressing p53 protein did not change significantly over the study period, and thus did not correlate with changes in the differentiation of SCC. Conclusions—The decreasing incidence of viral infection correlates strongly with the falling numbers of SCC cases, especially well differentiated cases. These findings suggest that HPV might be involved in the development of SCC of the lung, affecting the histological differentiation of SCC in particular, at least in Okinawa, a subtropical island in southern Japan. Key Words: squamous cell carcinoma of the lung • histological differentiation • human papillomaviru