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.