HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients

被引：544

作者：

Castellsague, Xavier ^{[1
,2
]}

Alemany, Laia ^{[1
,2
]}

Quer, Miquel ^{[3
]}

Halec, Gordana ^{[4
]}

Quiros, Beatriz ^{[1
]}

Tous, Sara ^{[1
]}

Clavero, Omar ^{[1
]}

Alos, Llucia ^{[5
]}

Biegner, Thorsten ^{[6
]}

Szafarowski, Tomasz ^{[7
]}

Alejo, Maria ^{[8
]}

Holzinger, Dana ^{[4
]}

Cadena, Enrique ^{[9
,10
]}

Claros, Edith ^{[11
]}

Hall, Gillian ^{[12
]}

Laco, Jan ^{[13
,14
]}

Poljak, Mario ^{[15
]}

Benevolo, Maria ^{[16
]}

Kasamatsu, Elena ^{[17
]}

Mehanna, Hisham ^{[18
]}

Ndiaye, Cathy ^{[19
]}

Guimera, Nuria ^{[20
]}

Lloveras, Belen ^{[21
]}

Leon, Xavier ^{[3
]}

Ruiz-Cabezas, Juan C. ^{[22
]}

Alvarado-Cabrero, Isabel ^{[23
]}

Kang, Chang-Suk ^{[24
]}

Oh, Jin-Kyoung ^{[25
,26
]}

Garcia-Rojo, Marcial ^{[27
]}

Iljazovic, Ermina ^{[28
]}

Ajayi, Oluseyi F. ^{[29
]}

Duarte, Flora ^{[30
]}

Nessa, Ashrafun ^{[31
]}

Tinoco, Leopoldo ^{[32
]}

Duran-Padilla, Marco A. ^{[33
]}

Pirog, Edyta C. ^{[34
]}

Viarheichyk, Halina ^{[35
]}

Morales, Hesler ^{[36
]}

Costes, Valerie ^{[37
]}

Felix, Ana ^{[38
]}

Germar, Maria Julieta V. ^{[39
]}

Mena, Marisa ^{[1
]}

Ruacan, Arzu ^{[40
,41
]}

Jain, Asha ^{[42
]}

Mehrotra, Ravi ^{[43
,44
]}

Goodman, Marc T. ^{[45
,46
]}

Lombardi, Luis Estuardo ^{[47
]}

Ferrera, Annabelle ^{[48
]}

Malami, Sani ^{[49
]}

Albanesi, Estela I. ^{[50
]}

机构：

[1] IDIBELL, Catalan Inst Oncol ICO, Canc Epidemiol Res Program, Lhospitalet De Llobregat, Catalonia, Spain

[2] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[3] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[4] German Canc Res Ctr, Heidelberg, Germany

[5] Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain

[6] Univ Hosp Tuebingen, Dept Pathol, Tubingen, Germany

[7] Med Univ Warsaw, Czerniakowski Hosp, Fac Med & Dent, Dept Otorhinolaryngol, Warsaw, Poland

[8] Hosp Gen Hosp, Barcelona, Spain

[9] Inst Nacl Cancerol, Bogota, Colombia

[10] Univ Nacl Colombia, Bogota, Colombia

[11] Insituto Oncol Oriente Boliviano, Lab Privado Patol Oncos, Santa Cruz, Bolivia

[12] Manchester Royal Infirm, Oxford Rd, Manchester M13 9WL, Lancs, England

[13] Charles Univ Prague, Fac Med, Fingerland Dept Pathol, Hradec Kralove, Czech Republic

[14] Univ Hosp, Hradec Kralove, Czech Republic

[15] Univ Ljubljana, Fac Med, Inst Microbiol & Immunol, Ljubljana, Slovenia

[16] Regina Elena Inst Canc Res, Rome, Italy

[17] Univ Nacl Asuncion, Inst Invest Ciencias Salud, Asuncion, Paraguay

[18] Univ Birmingham, Inst Head & Neck Studies & Educ, Birmingham, W Midlands, England

[19] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ, Canada

[20] DDL Diagnost Lab, Rijswijk, Netherlands

[21] Univ Pompeu Fabra, Hosp del Mar IMIM, Dept Pathol, Barcelona, Spain

[22] Hosp SOLCA, Lab Clin & Mol, Guayaquil, Ecuador

[23] IMSS Mexico, Ctr Med Nacl Siglo 21, Hosp Oncol, Mexico City, DF, Mexico

[24] Catholic Univ Korea, Yeouido St Marys Hosp, Seoul, South Korea

[25] Natl Canc Ctr, Grad Sch Canc Sci & Policy, Goyang, South Korea

[26] Natl Canc Ctr, Natl Canc Control Inst, Goyang, South Korea

[27] Hosp Gen Jerez de la Frontera, Cadiz, Spain

[28] Univ Clin Ctr, Dept Pathol, Tuzla, Bosnia & Herceg

[29] Univ Lagos, Coll Med, Dept Oral Pathol, Lagos, Nigeria

[30] Ctr Canc Emma Romero Callejas, Tegucigalpa, Honduras

[31] Bangabandhu Sheikh Mujib Med Univ, Dept Obstet & Gynecol, Dhaka, Bangladesh

[32] Hosp Oncol SOLCA, Quito, Ecuador

[33] Hosp Gen Mexico City, Dept Pathol, Mexico City, DF, Mexico

[34] New York Hosp, Cornell Med Ctr, New York, NY 10021 USA

[35] Gomel State Med Univ, Gomel, BELARUS

[36] Inst Cancerol Dr Bernardo del Valle S, Guatemala City, Guatemala

[37] CHRU Gui De Chauliac, Montpellier, France

[38] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal

[39] Univ Philippines, Coll Med, Manila, Philippines

[40] Koc Univ, Sch Med, Istanbul, Turkey

[41] Hacettepe Univ, Sch Med, Ankara, Turkey

[42] Canc Prevent & Relief Soc, Raipur, Madhya Pradesh, India

[43] MLN Med Coll, Allahabad, Uttar Pradesh, India

[44] Inst Cytol & Prevent Oncol ICMR, Noida, Uttar Pradesh, India

[45] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96822 USA

[46] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[47] Hosp Gen San Juan de Dios, Ctr Invest Epidemiol Salud Sexual Reprod CIESAR, Guatemala City, Guatemala

[48] Univ Nacl Autonoma Honduras, Escuela Microbiol, Tegucigalpa, Honduras

[49] Bayero Univ, Kano, Nigeria

[50] Minist Salud Prov Buenos Aires, Buenos Aires, DF, Argentina

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2016年 / 108卷 / 06期

关键词：

HUMAN-PAPILLOMAVIRUS TYPES; SQUAMOUS-CELL CARCINOMAS; WORLDWIDE; RNA; DNA;

D O I：

10.1093/jnci/djv403

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Methods: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. Results: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6* I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. Conclusions: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

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