A different entity: a population based study of characteristics and recurrence patterns in oropharyngeal squamous cell carcinomas

Journal of Otolaryngology-Head & Neck Surgery

Stephanie L. Snow³  Murali Rajaraman¹  Robert D. Hart⁵  Kara Thompson⁴  Michael N. Ha²  Scott Murray² 

[1] Department of Radiation Oncology, Capital District Health Authority, Halifax, Nova Scotia, Canada;Dalhousie University, Faculty of Medicine, Halifax, Nova Scotia, Canada;Department of Internal Medicine, Division of Medical Oncology, Capital District Health Authority, Halifax, Nova Scotia, Canada;Dalhousie University, Research Methods Unit, Halifax, Nova Scotia, Canada;Department of Surgery, Division of Otolaryngology, Capital District Health Authority, Halifax, Nova Scotia, Canada

关键词: Staging;    Head and neck cancer;    p16;    Human papillomavirus;    Oropharyngeal squamous cell carcinoma;   

Others  :  1226222
DOI  :  10.1186/s40463-015-0082-6

 received in 2015-04-21, accepted in 2015-08-09,  发布年份 2015

【 摘 要 】

Background

Cases of squamous cell carcinoma (SCC) of the oropharynx were compared with other head and neck cancer (HNC) anatomic subsites in patients treated at the provincial referral centre for HNC, the Nova Scotia Cancer Centre (NSCC).

Methods

A retrospective chart review was performed on HNC patients assessed at the NSCC between 2010 and 2011. Patient demographics, disease characteristics, treatment details and outcomes, including recurrence rates and survival were collected. Data was collected on new and recurrent cases of HNC. This data was compared between the two types of HNC using chi-square tests for dichotomous categorical variables or Fishers exact test where appropriate. Wald test was used to compare categorical variables with 3 categories. Continuous variables were compared using the non-parametric Wilcoxon test.

Results

318 charts were included in the analysis. 122 (38 %) were oropharyngeal squamous cell carcinomas (OPSCCs). In terms of disease characteristics, OPSCCs were more likely to be poorly differentiated/undifferentiated (n = 267, 49(40 %) vs 42(21 %), p < 0.001), non-keratinizing (n = 169, 25(20 %) vs 17(9 %), p < 0.001), greater than 2 cm (n = 253, 72(59 %) vs 78(40 %), p = 0.0061), stage 4 (n = 313, 55(45 %) vs 64(33 %), p = 0.0315) and have had locoregional nodal spread (n = 315, 103(84 %) vs 55(28 %), p < 0.001). In the subset of 57 patients that had p16 testing, OPSCCs were more likely to be p16(+) (37(30 %) vs 1(1 %), p < .001). There were no significant differences in terms of Charlson probability of 10 year survival, smoking or alcohol consumption although OPSCC patients were significantly less likely to have COPD as a co-morbidity (n = 318, 19(16 %) vs 53(27 %), p = 0.0175). Finally, OPSCCs had less chance for relapse than non-OPSCCs in both univariate (2.119 times less, p=0.0034) and multivariate (1.899 times less, p=0.0505) analyses along with a 1.822 times less overall mortality in a multivariae analysis (p=0.0408). 

Conclusions

This analysis suggests that Nova Scotian OPSCCs should be considered distinct from other HNC lesions, most notably in terms of disease characteristics and prognosis. Specifically, despite a higher association with disease factors traditionally considered to be linked to poor prognosis, outcomes were actually superior in terms of relapse and overall mortality.

【 授权许可】

   
2015 Murray et al.

【 图 表 】

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【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61:69-90.
• [2]Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009; 45:309-316.
• [3]Canadian Cancer Statistics 2014. http://www. cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2014-EN.pdf webcite
• [4]Johnson-Obaseki S, McDonald JT, Corsten M, Rourke R. Head and neck cancer in Canada: trends 1992 to 2007. Otolaryngol Head Neck Surg. 2012; 147:74-78.
• [5]Attner P, Du J, Nasman A, Hammarstedt L, Ramqvist T, Lindholm J et al.. The role of human papillomavirus in the increased incidence of base of tongue cancer. Int J Cancer. 2010; 126:2879-2884.
• [6]Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008; 26:612-619.
• [7]Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME et al.. Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003. Cancer. 2008; 113:2901-2909.
• [8]Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G et al.. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009; 125:362-366.
• [9]Ramqvist T, Dalianis T. An epidemic of oropharyngeal squamous cell carcinoma (OSCC) due to human papillomavirus (HPV) infection and aspects of treatment and prevention. Anticancer Res. 2001; 31:1515-1520.
• [10]Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S et al.. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013; 31:4550-4559.
• [11]Chaturvedi AK, Engels EA, Pfeiffer R, Hernandez BY, Xiao W, Kim E et al.. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011; 29:4924-4301.
• [12]Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C et al.. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 2009; 18:541-550.
• [13]Health Canada tobacco use statistics. http://www. hc-sc.gc.ca/hc-ps/tobac-tabac/research-recherche/stat/index-eng.php webcite
• [14]Health Canada drug and alcohol use statistics. http://www. hc-sc.gc.ca/hc-ps/drugs-drogues/stat/index-eng.php webcite
• [15]Romanitan M, Nasman A, Ramqvist T, Dahlstrand H, Polykretis L, Vogiatzis P et al.. Human papillomavirus frequency in oral and oropharyngeal cancer in Greece. Anticancer Res. 2008; 28:2077-2080.
• [16]Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P et al.. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003; 95:1772-1783.
• [17]Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al.. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12-19.
• [18]Gillison M, D’Souza G, Westra W, Sugar E, Xiao W, Begum S et al.. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16‐ negative head and neck cancers. J Natl Cancer Inst. 2008; 100:407-420.
• [19]Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus‐ related cancer epidemic. Lancet Oncol. 2010; 11:781-789.
• [20]Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007; 121:1813-1820.
• [21]Pfister DG, Fury MG. New Chapter in Our Understanding of Human Papillomavirus-Related Head and Neck Cancer. J Clin Oncol. 2014;32. in press.
• [22]Fakhry C, Zhang Q, Nguyen-Tan PF, Rosenthal D, El-Naggar A, Garden AS et al.. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014.
• [23]Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005; 14:467-475.
• [24]Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994; 47:1245-1251.
• [25]Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999; 94:496-509.
• [26]Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF et al.. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2011; 363:24-35.
• [27]Statistics Canada: Smokers, by sex, province and territories (percent). http://www. statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health74b-eng.htm webcite
• [28]Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al.. Improved survival of patients with human papillomavirus‐ positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 100:261-269.
• [29]Lindquist D, Romanitan M, Hammarstedt L, Näsman A, Dahlstrand H, Lindholm J et al.. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol. 2007; 1:350-355.
• [30]Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS et al.. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008; 26:3582-3589.
• [31]O’Connell D, Seikaly H, Murphy R, Fung C, Cooper T, Knox A et al.. Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study. J Otolaryngol Head Neck Surg. 2013; 42:31. BioMed Central Full Text
• [32]Ferris RL, Harry Q, Panian B. Phase II Randomized Trial of Transoral Surgical Resection followed by Low-dose or Standard-dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer. 2013. ClinicalTrials. gov identifier: NCT01898494. https://clinicaltrials.gov/ct2/show/NCT01898494
• [33]Haughey BH. Adjuvant De-escalation, Extracapsular spread, P16+, Transoral (A.D.E.P.T) Trial for Oropharynx Malignancy. 2013. ClinicalTrials. gov identifier: NCT01687413. https://clinicaltrials.gov/ct2/show/NCT01687413
• [34]O’Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B et al.. Deintensification candidate subgroups in human papillomavirus–related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013; 31:543-550.
• [35]Nichols AC, Yoo J, Hammond JA, Fung K, Winquist E, Read N et al.. Early-stage squamous cell carcinoma of the oropharynx: radiotherapy vs. trans-oral robotic surgery (ORATOR) — study protocol for a randomized phase II trial. BMC Cancer. 2013; 13:133. BioMed Central Full Text
• [36]Klozar J, Koslabova E, Kratochvil V, Salakova M, Tachezy R. Nodal status is not a prognostic factor in patients with HPV-positive oral/oropharyngeal tumors. J Surg Oncol. 2013; 107:625-633.
• [37]Hong AM, Martin A, Armstrong BK, Lee CS, Jones D, Chatfield MD et al.. Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer. Ann Oncol. 2013; 24:215-219.
• [38]Smith EM, Ritchie JM, Summersgill KF, Klussmann JP, Lee JH, Wang D et al.. Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer. 2004; 108:766-772.
• [39]Hong AM, Dobbins TA, Lee CS, Jones D, Harnett GB, Armstrong BK et al.. Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 2010; 103:1510-1517.
• [40]Groome PA, Schulze KM, Mackillop WJ, Grice B, Goh C, Cummings BJ et al.. A comparison of published head and neck stage groupings in carcinomas of the tonsillar region. Cancer. 2001; 92:1484-1494.
• [41]Jones GW, Browman G, Goodyear M, Marcellus D, Hodson DI. Comparison of the additions of T and N integer scores with TNM stage groups in head and neck cancer. Head Neck. 1993; 15:497-503.
• [42]Hart AA, Hilgers FJ, Manni JJ. The importance of correct stage grouping in oncology. Cancer. 1995; 11:2656-2662.
• [43]Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L et al.. Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus–related oropharyngeal carcinomas. J Clin Oncol. 2015; 33:836-845.
• [44]Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM et al.. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma. J Clin Oncol. 2014.
• [45]Herrero R, Quint W, Hildesheim A, Gonzalez P, Struijk L, Katki HA et al.. Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One. 2013; 8:e68329.
• [46]Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C et al.. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011; 364:401-411.
• [47]Lastra RR, Pramick MR, Nakashima MO, Weinstein GS, Montone KT, Livolsi VA et al.. Adequacy of fine-needle aspiration specimens for human papillomavirus infection molecular testing in head and neck squamous cell carcinoma. Cytojournal. 2013; 10:21.