HPV Positive Bronchopulmonary Carcinomas in Women with Previous High-grade Cervical Intraepithelial Neoplasia (CIN III)

Abstract

A significant higher incidence of some cancers, especially lung cancer, has been found in women with previous HPV-related (human papillomavirus) urogenital and anal neoplasias than in individuals without this particular clinical history. The aim of our study was to investigate whether HPV is present in both CIN III (cervical intraepithelial neoplasia) lesions and bronchopulmonary second primary cancers in women with a clinical history of both diseases. Paraffin-embedded tumour tissue from 75 patients with bronchopulmonary carcinomas was examined using the polymerase chain reaction (PCR) technique and in situ hybridization for the presence of human HPV. In total, 51 primary tumours without metastases, 11 primary tumours with metastases and 13 lymph node metastases without available tissue from primary tumours were analysed. In our study 37/75 primary bronchopulmonary tumours (49%) were identified as HPV positive by the PCR method: 18 cases were purely HPV 16 positive (49%), 12 were purely HPV 6 positive (32%), 5 cases were HPV 16/6 positive (14%), 1 case was HPV 16/11 positive (2%) and 1 case was HPV 16/18 positive (2%). Fourteen metastases were HPV positive, and HPV 16, 11 and 6 were detected in both regional and distant metastases. Two of the HPV 16-positive metastases were brain metastases from two separate HPV 16-positive primary tumours; 35% of the HPV-positive cases were adenocarcinomas, 30% squamous cell carcinomas, 22% oat cell carcinomas, 5% large cell carcinomas, 3% anaplastic carcinoma, 3% low-differentiated carcinoma, and 3% malignant cylindroma. The CIN III lesions from 34 of the 37 HPV-positive bronchopulmonary carcinomas were analysed by PCR. The overall HPV positivity in the CIN III lesions was 74% (25/34 cases): 48% were purely HPV 16 positive, 24% purely HPV 6 positive, 24% HPV 16/6 positive and 4% were HPV 18 positive. Our results indicate that HPV is also involved in the development of bronchopulmonary cancers in women with a history of CIN III lesions.