title: Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas.
abstract: A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Baba
authors.forename: Andres
authors.initials: A
authors.lastname: Castillo
authors.forename: Chihaya
authors.initials: C
authors.lastname: Koriyama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yanagi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Karem Y
authors.initials: KY
authors.lastname: Shuyama
authors.forename: Noureen
authors.initials: N
authors.lastname: Khan
authors.forename: Michiyo
authors.initials: M
authors.lastname: Higashi
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Itoh
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Eizuru
authors.forename: Takashi
authors.initials: T
authors.lastname: Aikou
authors.forename: Suminori
authors.initials: S
authors.lastname: Akiba
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D015995:Prevalence; D011799:Quinazolines / Q000627:therapeutic use*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011799:Quinazolines; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D000077156:Gefitinib