High-risk human papillomavirus-positive lung cancer: molecular evidence for a pattern of pulmonary metastasis

R.A.A. van Boerdonk, J.M.A. Daniels, E. Bloemena, O. Krijgsman, R.D.M. Steenbergen, R.H. Brakenhoff, K. Grünberg, B. Ylstra, C.J.L.M. Meijer, E.F. Smit, P.J.F. Snijders, D.A.M. Heideman

Research output: Contribution to JournalArticleAcademicpeer-review


Introduction: Infection with high-risk types of human papillomavirus (hrHPV) is associated with cervical, anogenital, and oropharyngeal cancers. Since a causal contribution of hrHPV infection to lung cancer (LC) is still a matter of debate, a comprehensive study was performed to delineate hrHPV involvement in LC, using a Dutch study population.

Methods: Archival tissue specimens from 223 patients (145 men, 78 women, median age 65 years, range 27-87 years), who presented with cancer in the lungs, were subjected to GP5+/6+ polymerase chain reaction and p16INK4A immunohistochemistry. The series included primary lung carcinomas of patients without a history of cancer (n = 175), primary lung carcinomas of patients with an unrelated cancer in the past (n = 36), and carcinomas with primary presentation in the lungs of which the origin (i.e., primary or metastasis) was equivocal at the time of diagnosis (n = 12). GP5+/6+ polymerase chain reaction/p16INK4A double-positive carcinomas were subjected to HPV genotyping, HPVE7 transcript analysis, loss of heterozygosity analysis, and array-comparative genomic hybridization.

Results: Whereas all primary lung carcinomas were hrHPV-negative (211 of 211, 100%), three hrHPV-positive equivocal carcinomas (3 of 12, 25%) were identified. These patients (1 male, 2 females) had a history of hrHPV-associated disease; one tonsillar and two cervical carcinomas. A clonal relationship between individual tumor pairs was supported by identical hrHPV genotype, pattern of p16INK4A expression, HPVE7 mRNA expression, and genomic aberrations.

Conclusions: hrHPV presence in a tumor with primary presentation in the lungs signifies pulmonary metastasis from a primary hrHPV-positive cancer elsewhere in the body. No support was found for an attribution of hrHPV infection to the development of primary LC.

Original languageEnglish
Pages (from-to)711-718
JournalJournal of Thoracic Oncology
Issue number6
Publication statusPublished - 2013


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