The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

Cancer Prevention and Control Program Fox Chase Cancer Center Temple Health Philadelphia PA USA

Central Clinical School The University of Sydney Sydney NSW Australia

Department of Biostatistics Fox Chase Cancer Center Temple Health Philadelphia PA USA

Department of Epidemiology and Biostatistics Temple University College of Public Health Philadelphia PA USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Human Genetics Graduate School of Public Health University of Pittsburgh Pittsburgh PA USA

Department of Immunology Institute of Hematology and Blood Transfusion National Reference Laboratory for Papillomaviruses Prague Czech Republic

Department of Internal Medicine Division of Hematology Oncology University of Michigan Ann Arbor MI USA

Department of Medical Microbiology Faculty of Medicine University of Debrecen Hungary

Department of Molecular Medicine Unit of Pathology University of Pavia and à IRCCS Policlinico S Matteo Foundation Pavia Italy

Department of Oral and Maxillofacial Surgery Plastic Surgery University Medical Center of the Johannes Gutenberg University Mainz Germany

Department of Otolaryngology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung Taiwan

Department of Otolaryngology Research Institute and Hospital National Cancer Center Gyeonggi do Korea

Department of Otolaryngology Temple University; and Fox Chase Cancer Center Philadelphia PA USA

Department of Otorhinolaryngology Head and Neck Surgery Graduate School of Medicine University of the Ryukyus Okinawa Japan

Department of Otorhinolaryngology Head and Neck Surgery GROW Institute Maastricht University Medical Centre Maastricht The Netherlands

Department of Pathology and Anatomical Sciences SUNY at the University at Buffalo Buffalo NY USA

Department of Pathology and Immunology Washington University School of Medicine St Louis MO USA

Department of Pathology and Laboratory Medicine Western Connecticut Health Network Danbury Hospital Danbury CT USA

Department of Pathology Microbiology and Immunology Vanderbilt University Nashville TN 37232 USA

Department of Sciences of Public Health and Pediatrics University of Turin Turin Italy

Department of Surgery Head and Neck Service Memorial Sloan Kettering Cancer Center New York NY USA

Departments of Population Health Science and Policy of Thoracic Surgery and Institute For Translational Epidemiology Icahn School of Medicine at Mount Sinai New York NY USA

Genomic Medicine Institute Cleveland Clinic Lerner Research Institute Cleveland OH USA

Institute of Otolaryngology Università Cattolica del Sacro Cuore Policlinico Agostino Gemelli Rome Italy

Non Communicable Diseases Research Programme Kenya Medical Research Institute Nairobi Kenya

Zobrazit více v PubMed

Ferlay J., et al. (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 Lyon, France: International Agency for Research on Cancer.

Chaturvedi A.K., et al. (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J. Clin. Oncol., 29, 4294–4301. PubMed PMC

Gillison M.L., et al. (2012) Prevalence of oral HPV infection in the United States, 2009–2010. JAMA, 307, 693–703. PubMed PMC

Hobbs C.G., et al. (2006) Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin. Otolaryngol., 31, 259–266. PubMed

Syrjanen S., et al. (2011) Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. Oral Dis., 17 (suppl. 1), 58–72. PubMed

Ragin C.C., et al. (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int. J. Cancer, 121, 1813–1820. PubMed

Zandberg D.P., et al. (2014) Oropharyngeal cancer is a driver of racial outcome disparities in squamous cell carcinoma of the head and neck: 10-year experience at the University of Maryland Greenebaum Cancer Center. Head Neck., 4, 564–572. PubMed PMC

Chernock R.D., et al. (2011) Human papillomavirus-related squamous cell carcinoma of the oropharynx: a comparative study in whites and African Americans. Arch. Otolaryngol. Head Neck Surg., 137, 163–169. PubMed PMC

Settle K., et al. (2009) Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev. Res. (Phila Pa), 2, 776–781. PubMed PMC

Worsham M.J., et al. (2013) Improved survival with HPV among African Americans with oropharyngeal cancer. Clin. Cancer Res., 19, 2486–2492. PubMed PMC

Ndiaye C., et al. (2014) HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol., 15, 1319–1331. PubMed

Kruger M., et al. (2014) The prevalence of human papilloma virus (HPV) infections in oral squamous cell carcinomas: a retrospective analysis of 88 patients and literature overview. J. Craniomaxillofac.Surg., 42, 1506–1514. PubMed

Mehanna H., et al. (2013) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Head Neck, 35, 747–755. PubMed

Dayyani F., et al. (2010) Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol., 2, 15. PubMed PMC

Stein A.P., et al. (2014) Prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in the United States across time. Chem. Res. Toxicol., 27, 462–469. PubMed PMC

Ragin C.C., et al. (2006) 11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours. Br. J. Cancer, 95, 1432–1438. PubMed PMC

Ukpo O.C., et al. (2009) Human papillomavirus-associated oropharyngeal squamous cell carcinomas: primary tumor burden and survival in surgical patients. Ann. Otol. Rhinol. Laryngol., 118, 368–373. PubMed

Wang X.I., et al. (2012) Changing trends in human papillomavirus-associated head and neck squamous cell carcinoma. Ann. Diagn. Pathol., 16, 7–12. PubMed

Newcombe R.G. (1998) Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat. Med., 17, 857–872. PubMed

Higgins J.P.T., et al. (2003) Measuring inconsistency in meta-analyses. BMJ, 327, 557–560. PubMed PMC

Egger M., et al. (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629–634. PubMed PMC

Van Rensburg E.J., et al. (1995) Detection of human papillomavirus DNA with in situ hybridisation in oral squamous carcinoma in a rural black population. S. Afr. Med. J., 85, 894–896. PubMed

Gillison M.L., et al. (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J. Natl. Cancer Inst., 92, 709–720. PubMed

Boy S., et al. (2006) HPV detection in primary intra-oral squamous cell carcinomas--commensal, aetiological agent or contamination? J. Oral Pathol. Med., 35, 86–90. PubMed

Agrawal Y., et al. (2008) Oral human papillomavirus infection before and after treatment for human papillomavirus 16-positive and human papillomavirus 16-negative head and neck squamous cell carcinoma. Clin. Cancer Res., 14, 7143–7150. PubMed PMC

Lewis J.S., Jr., et al. (2010) p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am. J .Surg. Pathol., 34, 1088–1096. PubMed PMC

Jalouli J., et al. (2012) Human papilloma virus, herpes simplex virus and epstein barr virus in oral squamous cell carcinoma from eight different countries. Anticancer Res., 32, 571–580. PubMed

Jiron J., et al. (2014) Racial disparities in human papillomavirus (HPV) associated head and neck cancer. Am. J. Otolaryngol., 35, 147–153. PubMed PMC

Stephen J.K., et al. (2012) Human papillomavirus outcomes in an access-to-care laryngeal cancer cohort. Otolaryngol. Head Neck Surg., 146, 730–738. PubMed PMC

Babiker A.Y., et al. (2013) Screening for high risk human papilloma virus (HR-HPV) subtypes, among Sudanese patients with oral lesions. Int. J. Clin. Exp. Med., 6, 275–281. PubMed PMC

Isayeva T., et al. (2014) African Americans with oropharyngeal carcinoma have significantly poorer outcomes despite similar rates of human papillomavirus-mediated carcinogenesis. Hum. Pathol., 45, 310–319. PubMed

Ndiaye C., et al. (2013) The role of human papillomavirus in head and neck cancer in Senegal. Infect. Agent Cancer, 8, 14. PubMed PMC

Salazar C.R., et al. (2014) Human papillomavirus-associated head and neck squamous cell carcinoma survival: a comparison by tumor site and initial treatment. Head Neck Pathol., 8, 77–87. PubMed PMC

Isayeva T., et al. (2015) The protective effect of p16(INK4a) in oral cavity carcinomas: p16(Ink4A) dampens tumor invasion-integrated analysis of expression and kinomics pathways. Mod. Pathol., 28, 631–653. PubMed

Liu J.C., et al. (2015) High prevalence of discordant human papillomavirus and p16 oropharyngeal squamous cell carcinomas in an African American cohort. Head Neck. 38 (suppl. 1), E867–E872. PubMed PMC

Cruz I.B., et al. (1996) Age-dependence of human papillomavirus DNA presence in oral squamous cell carcinomas. Eur. J. Cancer B Oral Oncol., 32B, 55–62. PubMed

Tsuhako K., et al. (2000) Comparative study of oral squamous cell carcinoma in Okinawa, Southern Japan and Sapporo in Hokkaido, Northern Japan; with special reference to human papillomavirus and Epstein-Barr virus infection. J. Oral Pathol. Med., 29, 70–79. PubMed

Koskinen W.J., et al. (2003) Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int. J. Cancer, 107, 401–406. PubMed

De Petrini M., et al. (2006) Head and neck squamous cell carcinoma: role of the human papillomavirus in tumour progression. New Microbiol., 29, 25–33. PubMed

Al-Swiahb J.N., et al. (2010) Prognostic impact of p16, p53, epidermal growth factor receptor, and human papillomavirus in oropharyngeal cancer in a betel nut-chewing area. Arch. Otolaryngol. Head Neck Surg., 136, 502–508. PubMed

Armas G.L., et al. (2008) The impact of virus in N3 node dissection for head and neck cancer. Eur. Arch. Otorhinolaryngol., 265, 1379–1384. PubMed

Cohen M.A., et al. (2008) Increased viral load correlates with improved survival in HPV-16-associated tonsil carcinoma patients. Acta Otolaryngol., 128, 583–589. PubMed

Worden F.P., et al. (2008) Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J. Clin. Oncol., 26, 3138–3146. PubMed PMC

Major T., et al. (2005) The characteristics of human papillomavirus DNA in head and neck cancers and papillomas. J. Clin. Pathol., 58, 51–55. PubMed PMC

Feher E., et al. (2009) Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus. J. Med. Virol., 81, 1975–1981. PubMed

Straetmans J.M., et al. (2009) Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas. Laryngoscope, 119, 1951–1957. PubMed

Tachezy R., et al. (2009) Demographic and risk factors in patients with head and neck tumors. J. Med. Virol., 81, 878–887. PubMed

D’Souza G., et al. (2010) Moderate predictive value of demographic and behavioral characteristics for a diagnosis of HPV16-positive and HPV16-negative head and neck cancer. Oral Oncol., 46, 100–104. PubMed PMC

Bennett K.L., et al. (2010) HPV status-independent association of alcohol and tobacco exposure or prior radiation therapy with promoter methylation of FUSSEL18, EBF3, IRX1, and SEPT9, but not SLC5A8, in head and neck squamous cell carcinomas. Genes Chromosomes Cancer, 49, 319–326. PubMed

Kabeya M., et al. (2012) Prevalence of human papillomavirus in mobile tongue cancer with particular reference to young patients. Cancer Sci., 103, 161–168. PubMed

Hoffmann M., et al. (2012) HPV DNA, E6*I-mRNA expression and p16INK4A immunohistochemistry in head and neck cancer - how valid is p16INK4A as surrogate marker? Cancer Lett., 323, 88–96. PubMed

Park W.S., et al. (2012) Human papillomavirus in oropharyngeal squamous cell carcinomas in Korea: use of G1 cycle markers as new prognosticators. Head Neck, 34, 1408–1417. PubMed

Heusinkveld M., et al. (2012) Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer. Int. J. Cancer, 131, E74–E85. PubMed

Bussu F., et al. (2013) HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker? Br. J. Cancer, 108, 1157–1162. PubMed PMC

Bussu F., et al. (2014) Human papillomavirus (HPV) infection in squamous cell carcinomas arising from the oropharynx: detection of HPV DNA and p16 immunohistochemistry as diagnostic and prognostic indicators--a pilot study. Int. J. Radiat. Oncol. Biol. Phys., 89, 1115–1120. PubMed

Deng Z., et al. (2011) Prevalence and clinical features of human papillomavirus in head and neck squamous cell carcinoma in Okinawa, southern Japan. Eur. Arch. Otorhinolaryngol., 268, 1625–1631. PubMed

Deng Z., et al. (2013) Viral load, physical status, and E6/E7 mRNA expression of human papillomavirus in head and neck squamous cell carcinoma. Head Neck, 35, 800–808. PubMed

Morbini P., et al. (2013) Oral HPV infection and persistence in patients with head and neck cancer. Oral Surg. Oral Med. Oral Pathol. Oral Radiol., 116, 474–484. PubMed

Hong A., et al. (2013) HPV status of oropharyngeal cancer by combination HPV DNA/p16 testing: biological relevance of discordant results. Ann. Surg.Oncol., 20 (suppl. 3), S450–S458. PubMed

Morbini P., et al. (2015) Identification of transcriptionally active HPV infection in formalin-fixed, paraffin-embedded biopsies of oropharyngeal carcinoma. Hum. Pathol., 46, 681–689. PubMed

Fakhry C., et al. (2015) Oropharyngeal cancer survivorship in Denmark, 1977–2012. Oral Oncol., 51, 982–984. PubMed

de Souza D.L., et al. (2012) Trends in the incidence of oral cavity and oropharyngeal cancers in Spain. Head Neck, 34, 649–654. PubMed

Ang K.K., et al. (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N. Engl. J. Med., 363, 24–35. PubMed PMC

Fakhry C., et al. (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J. Natl. Cancer Inst., 100, 261–269. PubMed

Zandberg D.P., et al. (2015) Emergence of HPV16-positive oropharyngeal cancer in Black patients over time: University of Maryland 1992–2007. Cancer Prev. Res. (Phila), 8, 12–19. PubMed PMC

Salazar C.R., et al. (2014) Combined P16 and human papillomavirus testing predicts head and neck cancer survival. Int. J. Cancer, 135, 2404–2412. PubMed PMC

Junor E., et al. (2012) Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16-negative squamous cell carcinoma of the oropharynx. Br. J. Cancer, 106, 358–365. PubMed PMC

Gillison M.L., et al. (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J. Natl. Cancer Inst., 100, 407–420. PubMed

D’Souza G., et al. (2014) Differences in oral sexual behaviors by gender, age, and race explain observed differences in prevalence of oral human papillomavirus infection. PLoS One, 9, e86023. PubMed PMC

Rettig E.M., et al. (2016) Race is associated with sexual behaviors and modifies the effect of age on human papillomavirus serostatus among perimenopausal women. Sex Transm. Dis., 43, 231–237. PubMed

Xi L.F., et al. (1997) Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia. J. Natl. Cancer Inst., 89, 796–802. PubMed

Villa L.L., et al. (2000) Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia. J. Gen. Virol., 81, 2959–2968. PubMed

Berumen J., et al. (2001) Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J. Natl. Cancer Inst., 93, 1325–1330. PubMed

Hildesheim A., et al. (2001) Human papillomavirus type 16 variants and risk of cervical cancer. J. Natl. Cancer Inst., 93, 315–318. PubMed

Xi L.F., et al. (2002) Acquisition and natural history of human papillomavirus type 16 variant infection among a cohort of female university students. Cancer Epidemiol. Biomarkers Prev., 11, 343–351. PubMed

Tornesello M.L., et al. (2008) Human papillomavirus genotypes and HPV16 variants in penile carcinoma. Int. J. Cancer, 122, 132–137. PubMed