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Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer

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Abstract

Background

Patients with head and neck squamous cell carcinoma (HNSCC) are at significantly elevated risk of second primary malignancies (SPM), most commonly within the head and neck, lung, and esophagus (HNLE). Our objectives were to quantify the excess risk of SPM across all anatomic sites in which SPM risk is meaningfully elevated, including non-HNLE sites, in a large cohort of US patients.

Methods

Population-based analysis of 75,087 patients with HNSCC in the SEER program, quantifying excess SPM risk by integrating relative (standardized incidence ratio; SIR) and absolute (excess absolute risk per 10,000 person-years at risk; EAR) statistics.

Results

In HNSCC patients, the SIR of a second primary solid cancer was 2.2 (95% CI 2.1–2.2), corresponding to EAR of 167.7 additional cases per 10,000 person-years at risk. Over 1 year, 60 patients would need to be followed to observe one excess SPM. Lung cancer burden was most markedly elevated in absolute terms (EAR = 75.2), followed by HN (EAR = 59.8), esophageal (EAR = 14.2), and colorectal (EAR = 4.3) cancers. Lesser but significant excess risks were also observed for cancers of the bladder, liver, stomach, pancreas, kidney, salivary glands, nasopharynx, uterine cervix, and lymphoma.

Conclusions

Data from a large population-based US cohort reveals that HNSCC patients experience markedly excess risk of SPM, predominantly in the HNLE sites. Furthermore, the risk of SPM is also meaningfully elevated, although to a lesser degree, in multiple other tobacco-associated sites.

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References

  1. Yamamoto E, Shibuya H, Yoshimura R, Miura M (2002) Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma. Cancer 94:2007–2014

    Article  PubMed  Google Scholar 

  2. Sturgis EM, Miller RH (1995) Second primary malignancies in the head and neck cancer patient. Ann Otol Rhinol Laryngol 104:946–954

    PubMed  CAS  Google Scholar 

  3. Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J (1999) Second neoplasm in patients with head and neck cancer. Head Neck 21:204–210

    Article  PubMed  CAS  Google Scholar 

  4. Tepperman BS, Fitzpatrick PJ (1981) Second respiratory and upper digestive tract cancers after oral cancer. Lancet 2:547–549

    Article  PubMed  CAS  Google Scholar 

  5. Chuang SC, Scelo G, Tonita JM, Tamaro S, Jonasson JG, Kliewer EV, Hemminki K, Weiderpass E, Pukkala E, Tracey E, Friis S, Pompe-Kirn V, Brewster DH, Martos C, Chia KS, Boffetta P, Brennan P, Hashibe M (2008) Risk of second primary cancer among patients with head and neck cancers: a pooled analysis of 13 cancer registries. Int J Cancer 123:2390–2396

    Article  PubMed  CAS  Google Scholar 

  6. Vikram B (1984) Changing patterns of failure in advanced head and neck cancer. Arch Otolaryngol 110:564–565

    PubMed  CAS  Google Scholar 

  7. Garavello W, Ciardo A, Spreafico R, Gaini RM (2006) Risk factors for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 132:762–766

    Article  PubMed  Google Scholar 

  8. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6:963–968

    Article  PubMed  CAS  Google Scholar 

  9. Ha PK, Califano JA (2003) The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14:363–369

    Article  PubMed  Google Scholar 

  10. Boice JD Jr, Fraumeni JF Jr (1985) Second cancer following cancer of the respiratory system in Connecticut, 1935–1982. Natl Cancer Inst Monogr 68:83–98

    PubMed  Google Scholar 

  11. Veli EM, Schatzkin A (1999) Common environmental risk factors. In: Neugut AI (ed) Multiple primary cancers. Lippincott Williams & Wilkins, Philadelphia, pp 213–223

    Google Scholar 

  12. Gluckman JL, Crissman JD (1983) Survival rates in 548 patients with multiple neoplasms of the upper aerodigestive tract. Laryngoscope 93:71–74

    PubMed  CAS  Google Scholar 

  13. Cooper JS, Pajak TF, Rubin P, Tupchong L, Brady LW, Leibel SA, Laramore GE, Marcial VA, Davis LW, Cox JD et al (1989) Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience. Int J Radiat Oncol Biol Phys 17:449–456

    Article  PubMed  CAS  Google Scholar 

  14. de Vries N, Snow GB (1986) Multiple primary tumours in laryngeal cancer. J Laryngol Otol 100:915–918

    PubMed  Google Scholar 

  15. de Vries N, Van der Waal I, Snow GB (1986) Multiple primary tumours in oral cancer. Int J Oral Maxillofac Surg 15:85–87

    Article  PubMed  Google Scholar 

  16. Lin K, Patel SG, Chu PY, Matsuo JM, Singh B, Wong RJ, Kraus DH, Shaha AR, Shah JP, Boyle JO (2005) Second primary malignancy of the aerodigestive tract in patients treated for cancer of the oral cavity and larynx. Head Neck 27:1042–1048

    Article  PubMed  Google Scholar 

  17. Rennemo E, Zatterstrom U, Boysen M (2008) Impact of second primary tumors on survival in head and neck cancer: an analysis of 2, 063 cases. Laryngoscope 118:1350–1356

    Article  PubMed  Google Scholar 

  18. Jones AS, Morar P, Phillips DE, Field JK, Husband D, Helliwell TR (1995) Second primary tumors in patients with head and neck squamous cell carcinoma. Cancer 75:1343–1353

    Article  PubMed  CAS  Google Scholar 

  19. Sikora AG, Morris LG, Sturgis EM (2009) Bidirectional association of anogenital and oral cavity/pharyngeal carcinomas in men. Arch Otolaryngol Head Neck Surg 135:402–405

    Article  PubMed  Google Scholar 

  20. Do KA, Johnson MM, Lee JJ, Wu XF, Dong Q, Hong WK, Khuri FR, Spitz MR (2004) Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies. Cancer 101:2837–2842

    Article  PubMed  Google Scholar 

  21. Khuri FR, Kim ES, Lee JJ, Winn RJ, Benner SE, Lippman SM, Fu KK, Cooper JS, Vokes EE, Chamberlain RM, Williams B, Pajak TF, Goepfert H, Hong WK (2001) The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 10:823–829

    PubMed  CAS  Google Scholar 

  22. Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, Wingo PA, Howe HL, Anderson RN, Edwards BK (2004) Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 101:3–27

    Article  PubMed  Google Scholar 

  23. Harlan LC, Hankey BF (2003) The surveillance, epidemiology, and end-results program database as a resource for conducting descriptive epidemiologic and clinical studies. J Clin Oncol 21:2232–2233

    Article  PubMed  Google Scholar 

  24. Fritz A, Percy C, Jack A (2000) International classification of diseases for oncology. World Health Organization, Geneva

    Google Scholar 

  25. Warren S, Gates O (1932) Multiple primary malignant tumors: a survey of the literature and a statistical study. Cancer 16:1358–1414

    Google Scholar 

  26. Curtis RE, Ries LA (2006) Methods. In: Curtis RE, Freedman DM, Ron E, Ries LA, Hacker DG, Edwards BK, Tucker MA, Fraumeni JFJ (eds) New malignancies among cancer survivors: SEER cancer registries, 1973–2000. National Cancer Institute, Bethesda, pp 9–14

    Google Scholar 

  27. Schoenberg BS, Myers MH (1977) Statistical methods for studying multiple primary malignant neoplasms. Cancer 40:1892–1898

    Article  PubMed  CAS  Google Scholar 

  28. Begg CB, Zhang ZF, Sun M, Herr HW, Schantz SP (1995) Methodology for evaluating the incidence of second primary cancers with application to smoking-related cancers from the Surveillance, Epidemiology, and End Results (SEER) program. Am J Epidemiol 142:653–665

    PubMed  CAS  Google Scholar 

  29. Breslow NE, Day NE (1987) Statistical methods in cancer research. IARC, Lyon, France

  30. Freedman ND, Abnet CC, Leitzmann MF, Hollenbeck AR, Schatzkin A (2007) Prospective investigation of the cigarette smoking-head and neck cancer association by sex. Cancer 110:1593–1601

    Article  PubMed  Google Scholar 

  31. Hannan LM, Jacobs EJ, Thun MJ (2009) The association between cigarette smoking and risk of colorectal cancer in a large prospective cohort from the United States. Cancer Epidemiol Biomarkers Prev 18:3362–3367

    Article  PubMed  CAS  Google Scholar 

  32. IARC (2004) IARC monographs on the evaluation of carcinogenic risks to humans. In: IARC (ed) Tobacco smoke and involuntary smoking, vol 83. Lyon, France, pp 1179–1886

  33. Besson H, Brennan P, Becker N, De Sanjose S, Nieters A, Font R, Maynadie M, Foretova L, Cocco PL, Staines A, Vornanen M, Boffetta P (2006) Tobacco smoking, alcohol drinking and Hodgkin’s lymphoma: a European multi-centre case–control study (EPILYMPH). Br J Cancer 95:378–384

    Article  PubMed  CAS  Google Scholar 

  34. Nieters A, Deeg E, Becker N (2006) Tobacco and alcohol consumption and risk of lymphoma: results of a population-based case–control study in Germany. Int J Cancer 118:422–430

    Article  PubMed  CAS  Google Scholar 

  35. Nieters A, Rohrmann S, Becker N, Linseisen J, Ruediger T, Overvad K, Tjonneland A, Olsen A, Allen NE, Travis RC, Bingham S, Khaw KT, Ardanaz E, Redondo ML, Basterrechea M, Martinez C, Tormo MJ, Rosso S, Tagliabue G, Masala G, Mattiello A, Tumino R, Boeing H, Bergmann M, Kaaks R, Trichopoulou A, Trichopoulos D, Peeters PH, Bueno-de-Mesquita B, Boffetta P, Brennan P, Ferrari P, Neasham D, Lund E, Berglund G, Manjer J, Hallmans G, Johansson I, Vineis P, Riboli E (2008) Smoking and lymphoma risk in the European prospective investigation into cancer and nutrition. Am J Epidemiol 167:1081–1089

    Article  PubMed  Google Scholar 

  36. Hjalgrim H, Ekstrom-Smedby K, Rostgaard K, Amini RM, Molin D, Hamilton-Dutoit S, Schollkopf C, Chang ET, Ralfkiaer E, Adami HO, Glimelius B, Melbye M (2007) Cigarette smoking and risk of Hodgkin lymphoma: a population-based case–control study. Cancer Epidemiol Biomarkers Prev 16:1561–1566

    Article  PubMed  CAS  Google Scholar 

  37. Braakhuis BJ, Tabor MP, Leemans CR, van der Waal I, Snow GB, Brakenhoff RH (2002) Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24:198–206

    Article  PubMed  Google Scholar 

  38. Chen MC, Huang WC, Chan CH, Chen PT, Lee KD (2010) Impact of second primary esophageal or lung cancer on survival of patients with head and neck cancer. Oral Oncol 46:249–254

    Article  PubMed  CAS  Google Scholar 

  39. Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP (2001) Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol 19:1358–1362

    PubMed  CAS  Google Scholar 

  40. Day GL, Blot WJ, Shore RE, McLaughlin JK, Austin DF, Greenberg RS, Liff JM, Preston-Martin S, Sarkar S, Schoenberg JB et al (1994) Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86:131–137

    Article  PubMed  CAS  Google Scholar 

  41. Day GL, Blot WJ, Shore RE, Schoenberg JB, Kohler BA, Greenberg RS, Liff JM, Preston-Martin S, Austin DF, McLaughlin JK et al (1994) Second cancers following oral and pharyngeal cancer: patients’ characteristics and survival patterns. Eur J Cancer B Oral Oncol 30B:381–386

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Luc G. T. Morris.

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Morris, L.G.T., Sikora, A.G., Hayes, R.B. et al. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control 22, 671–679 (2011). https://doi.org/10.1007/s10552-011-9739-2

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  • DOI: https://doi.org/10.1007/s10552-011-9739-2

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