HPV Analysis in Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Squamous Cell Carcinoma

Abstract

For patients with head and neck squamous cell carcinoma (HNSqCC), the development of squamous cell carcinoma (SqCC) in the lung may signal a new primary or the onset of metastatic dissemination. Although the distinction influences prognosis and therapy, it may not be straightforward on histological or clinical grounds. Human papillomavirus (HPV) is an etiologic agent for SqCCs arising from the oropharynx, but not for SqCCs arising from other head and neck sites. For patients with HNSqCC who develop a lung SqCC, HPV analysis could be useful in establishing tumor relationships. High risk HPV in-situ hybridization was performed on 54 lung SqCCs from patients with a prior HNSqCC, and on 166 primary lung carcinomas from patients without prior HNSqCC. HPV was detected in 11 of 220 (5%) cases. All HPV-positive cases were from patients with a prior oropharyngeal SqCC. For the paired oropharyngeal and lung SqCCs, HPV status was concordant in 95% of cases. Time from treatment of the HPV-positive oropharyngeal carcinomas to detection of the lung carcinoma ranged from 1 to 97 months (mean 36 months). Two HPV-positive cancers were detected in the lung 8 years after treatment of the oropharyngeal primary. Despite the long interval, E6 sequencing analysis of one of these paired samples confirmed that the tumors harbored the same HPV-16 variant. HPV does not appear to play a role in the development of primary lung cancer. For patients with oropharyngeal SqCC who develop lung SqCCs, HPV analysis may be helpful in clarifying tumor relationships. These relationships may not be obvious on clinical grounds as HPV-related HNSqCC may metastasize long after treatment of the primary tumor.

Detection of human papillomavirus in non–small cell carcinoma of the lung

“…Sunnybrook Health Sciences Centre, 2075 range of HPV infection detected in lung ADC occurring in Asian populations varies from 0 to around 40% [7][8][9]. In contrast, several studies based on North American and European populations did not find an association between HPV infection and NSCLC [10][11][12][13]. A recent comprehensive meta-analysis [6] and an international pooled analysis [14] found that the variation in HPV detection rate may be a function of the geographical origin and histologic subtypes, rather than detection methods.…”

Exploration of the cancers association based on somatic data in TCGA

“…Some previous evidences have approved the common risk factors and molecular abnormalities in cell-cycle regulation and signal transduction predominate among these three cancers. For example, for those patients with head and neck squamous cell carcinoma, the development of squamous cell carcinoma in the lung may signal a new primary or the onset of metastatic dissemination [16]. Previous study suggested that the INK4a/p16 germline mutation associated with familial atypical multiple mole melanoma syndrome can also be associated with familial head and neck squamous cell carcinoma syndrome [17].…”

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

“…However, current data suggest that most of these HPV þ lung SCCs may represent metastasis from previous head and neck HPV þ SCC and uterine or cervical HPV þ lesions and SCC. 17,18 Basaloid carcinoma of the lung is an uncommon poorly differentiated NSCLC, probably akin to SCC. Histologically, the tumor is composed of relatively small cells with high numbers of mitotic figures showing a lobular pattern with peripheral palisading and comedo-type necrosis.…”