title: HPV-associated lung cancers: an international pooled analysis.
abstract: Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of cross-sectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship.
authors: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA, camille.ragin@fccc.edu.
authors: Camille
authors: C
authors: Ragin
authors: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors: Monisola
authors: M
authors: Obikoya-Malomo
authors: Biostatistics & Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors: Sungjin
authors: S
authors: Kim
authors: Biostatistics & Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors: Zhengjia
authors: Z
authors: Chen
authors: Department of Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
authors: Rafael
authors: R
authors: Flores-Obando
authors: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors: Denise
authors: D
authors: Gibbs
authors: Department of Epidemiology and Preventative Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
authors: Chihaya
authors: C
authors: Koriyama
authors: Virology Program, Instituto de Ciencias Biomédicas (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.
authors: Francisco
authors: F
authors: Aguayo
authors: Infections and Immunoepidemiology Branch and.
authors: Jill
authors: J
authors: Koshiol
authors: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Neil E
authors: NE
authors: Caporaso
authors: Department of Medical and Surgical Sciences, Faculty of Medicine, University of Foggia, Foggia, Italy.
authors: Giovanna E
authors: GE
authors: Carpagnano
authors: Laboratory of Molecular Virology, Foundation Polyclinic Tor Vergata, Rome, Italy.
authors: Marco
authors: M
authors: Ciotti
authors: Department of Medical Oncology, Hokkaido University, Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors: Hirotoshi
authors: H
authors: Dosaka-Akita
authors: Department and Cellular and Organ Pathology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita 010-8543, Japan.
authors: Masashi
authors: M
authors: Fukayama
authors: Department and Cellular and Organ Pathology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita 010-8543, Japan.
authors: Akiteru
authors: A
authors: Goto
authors: Faculty of Medicine, Laboratory of Clinical Virology, 5D10, University of Crete, Vassilika Voutes, 71110 Heraklion, Crete, Greece.
authors: Demetrios A
authors: DA
authors: Spandidos
authors: Laboratory of Histology & Embryology, School of Medicine, University of Athens, Athens, Greece.
authors: Vassilis
authors: V
authors: Gorgoulis
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Daniëlle A M
authors: DA
authors: Heideman
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert A A
authors: RA
authors: van Boerdonk
authors: Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada-Shinden, Yachiyo-shi, Chiba 276-8524, Japan.
authors: Kenzo
authors: K
authors: Hiroshima
authors: Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
authors: Reika
authors: R
authors: Iwakawa
authors: Laboratory of Histology & Embryology, School of Medicine, University of Athens, Athens, Greece.
authors: Nikolaos G
authors: NG
authors: Kastrinakis
authors: Department of Medical Oncology, Hokkaido University, Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors: Ichiro
authors: I
authors: Kinoshita
authors: Department of Epidemiology and Preventative Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
authors: Suminori
authors: S
authors: Akiba
authors: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Maria T
authors: MT
authors: Landi
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: H
authors: H
authors: Eugene Liu
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Jinn-Li
authors: JL
authors: Wang
authors: Department of Medical Oncology and Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors: Ranee
authors: R
authors: Mehra
authors: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors: Fadlo R
authors: FR
authors: Khuri
authors: Department of Medical Oncology, National Cancer Center Singapore, 11 Hospital Drive, Singapore 169610, Republic of Singapore.
authors: Wan-Teck
authors: WT
authors: Lim
authors: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors: Taofeek K
authors: TK
authors: Owonikoko
authors: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
authors: Suresh
authors: S
authors: Ramalingam
authors: Faculty of Medicine, Laboratory of Clinical Virology, 5D10, University of Crete, Vassilika Voutes, 71110 Heraklion, Crete, Greece.
authors: Emmanuela
authors: E
authors: Sarchianaki
authors: Department of Oncology & Radiotherapy, Turku University Hospital, Turku, Finland, Fundação Pio XII- Hospital de Câncer de Barretos, Barretos, Brazil.
authors: Kari
authors: K
authors: Syrjanen
authors: Department of Pathology and.
authors: Ming-Sound
authors: MS
authors: Tsao
authors: Department of Biostatistics, University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario M5G2M9, Canada.
authors: Jenna
authors: J
authors: Sykes
authors: Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK and.
authors: Siew Wan
authors: SW
authors: Hee
authors: Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
authors: Jun
authors: J
authors: Yokota
authors: Faculty of Medicine, Laboratory of Clinical Virology, 5D10, University of Crete, Vassilika Voutes, 71110 Heraklion, Crete, Greece.
authors: Apostolos
authors: A
authors: Zaravinos
authors: Department of Population Health, North Shore Long Island Jewish Health System, Hofstra Medical School, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, USA.
authors: Emanuela
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authors: Taioli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics*; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology; D015995:Prevalence; D016662:Virus Integration