Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), partic ularly the well-differentiated form, is the most frequent type of lung canc er, while this form is relatively rare on the Japanese mainland and in othe r countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it wi th non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon a nalysis), the prognosis of HPV-infected cases was found to be better than t hat of the non-infected cases. In the virus-infected cases, apoptosis and i nfiltration of a large number of Langerhans cells were demonstrated. In add ition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable p rognosis. However, among the virus-infected cases, the type 16 virus-infect ed cases showed a poorer prognosis, compared to those infected with other H PV types. p53 gene mutation was also examined, and was considered to be an unfavorabl e prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positi ve cases with p53 mutations showed a slightly better prognosis than did non -viral infected cases with p53 mutations. The TNM staging system was also u seful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treat ment. Chemotherapy and radiation therapy were not performed. Such treatment , however, might be effective, because virus-infected uterine cervical carc inomas have been routinely treated with chemotherapy and radiation. Further more, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy ma y be favorable for the clinical outcome.