title: Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients.
abstract: The reported prevalence for presence of human papillomavirus (HPV) genome in lung cancer varies across the world, and limited data are available for North America. P16 immunostaining is used as a surrogate marker for the presence of HPV in cervical and head and neck cancers. In non-small cell lung carcinoma (NSCLC), the association between P16 protein overexpression and HPV remains unclear. We investigated the presence of HPV genome by in situ hybridization (ISH) and polymerase chain reaction (PCR) and P16 or Rb protein expression by immunohistochemistry (IHC) in 336 surgically resected primary NSCLC: 204 adenocarcinoma (AdC) and 132 squamous cell carcinoma (SqCC). HPV genome was detected in 5 (1.5%) of 336 tumors studied by both ISH and PCR; all of them were typed as HPV16 and found in SqCC (3.8%). Despite being solitary tumors and clinically considered as primary lung cancers, all 5 patients had past history of HPV associated squamous cell carcinomas of other organ sites, thus highly suggestive of being metastases. P16 immunostaining was found in 137 (40.8%) tumors, with 109 (32.4%) showing high level expression. All HPV positive (+) cases showed P16 high expression. P16 and Rb protein expressions were inversely correlated (P<0.001), suggesting that the high P16 expression is largely driven by non-HPV loss of Rb protein expression. We conclude that HPV is not or rarely associated with NSCLC in Canadian and most likely North American patients, and P16 immunostaining is not a surrogate marker for its presence.
authors.affiliation: Department of Pathology, University Health Network, Princess Margaret Hospital site and Ontario Cancer Institute, Toronto, Ontario, Canada.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yanagawa
authors.forename: Ami
authors.initials: A
authors.lastname: Wang
authors.forename: Derek
authors.initials: D
authors.lastname: Kohler
authors.forename: Gilda da Cunha
authors.initials: Gda C
authors.lastname: Santos
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008175:Lung Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009656:North America; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D009363:Neoplasm Proteins