High-Risk HPV Status in Primary and Metastatic Carcinomas of the Lung.
Justin A Bishop, Peter B Illei, Edward Gabrielson, William H Westra. The Johns Hopkins Medical Institutions, Baltimore, MD
Background: Human papillomavirus (HPV) is the major causative agent in squamous cell carcinomas (SqCCs) of the cervix and oropharynx, but its role in lung cancer is unclear. Rates of HPV detection in lung cancer range from 0 – 80%. High detection rates may reflect to some degree the poor specificity of various non-quantitative PCR-based assays. The purpose of this study was to determine the presence of high risk HPV in primary lung carcinomas using a highly sensitive and specific in-situ hybridization (ISH) assay; and to determine the utility of HPV detection as a means of establishing tumor relationships in patients with head and neck SqCC who develop a SqCC in their lung.
Design: High risk HPV in-situ hybridization was performed on 146 primary lung carcinomas from patients without prior head and neck SqCCs, and on 49 lung SqCCs from patients with a prior head and neck SqCC.
Results: Overall, HPV was detected in 8 of 195 (4.1%) cases. HPV was not detected in any of the lung SqCCs from patients without a history of head and neck SqCC. All HPV-positive cases were from patients with a prior oropharyngeal SqCC (Table). For the paired oropharyngeal and lung SqCCs, concordant HPV status was confirmed in 94% of cases. The time interval from treatment of the HPV-positive oropharyngeal carcinomas to detection of the lung carcinoma ranged from 1 to 97 months (mean 41 months). Two HPV-positive cancers were detected in the lung 8 years after treatment of the oropharyngeal primary.
Conclusions: HPV does not appear to play any significant role in the development of primary lung cancer. For patients with oropharyngeal SqCC who develop SqCCs in their lungs, HPV analysis may be helpful in clarifying tumor relationships. These relationships may not be obvious on clinical grounds as HPV-related oropharyngeal SqCCs may metastasize long after treatment of the primary tumor.
|Tumor type||P16 IHC (%)||HPV ISH* (%)|
|Small cell carcinoma||3/3 (100)||0/3 (0)|
|Non-small cell carcinoma, NOS||1/12 (8)||0/12 (0)|
|Adenocarcinoma||15/74 (20)||0/74 (0)|
|Large cell/pleomorphic carcinoma||4/11 (25)||0/11 (0)|
|Squamous cell carcinoma|
|No prior squamous cell carcinoma||6/46 (13)||0/46 (0)|
|Prior head and neck squamous cell carcinoma||14/49 (29)||8/49 (16)|
|- oropharynx||12/24 (50)||8/24 (33)|
|- oral cavity||1/6 (17)||0/6 (0)|
|- larynx||1/20 (5)||0/20 (0)|
|- hypopharynx||0/1 (0)||0/1 (0)|