We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Preliminary Communication

Identifying patterns of failure and secondary primary malignancies in HPV-related oropharyngeal squamous cell carcinomas

    Ryan Holstead

    Department of Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11030

    ,
    Rehana Rasul

    Department of Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11030

    ,
    Anne Golden

    Department of Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11030

    ,
    Dev Kamdar

    Departement of Otolaryngology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11040

    ,
    Maged Ghaly

    Department of Radiation Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11042

    ,
    Sewit Teckie

    Department of Radiation Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11042

    ,
    Douglas Frank

    Departement of Otolaryngology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11040

    ,
    John Fantasia

    Department of Dental Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11040

    &
    Nagashree Seetharamu

    *Author for correspondence: Tel.: +1 516 734 8900;

    E-mail Address: Nseetharamu@northwell.edu

    Department of Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, NY USA, 11030

    Published Online:https://doi.org/10.2217/fon-2019-0673

    Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

    Papers of special note have been highlighted as: • of interest

    References

    • 1. Ferlay J, Shin H, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 127(12), 2893–2917 (2010).
    • 2. Masterson L, Moualed D, Liu ZW et al. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Eur. J. Cancer 50(15), 2636–2648 (2014).
    • 3. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global Cancer Statistics. CA Cancer J. Clin. 61(2), 69–90 (2011).
    • 4. Klussmann JP, Weissenborn SJ, Wieland U et al. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer 92(11), 2875–2884 (2001).
    • 5. Smith EM, Ritchie JM, Summersgill KF et al. Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Intl. J. Cancer 108(5), 116–133 (2003).
    • 6. Reed AL, Califan J, Cairns P et al. High frequency of p16 (CDKN2/MTS-1/INK4a) inactivation in head and neck squamous cell carcinoma. Cancer Res. 56(16), 3630–3633 (1996).
    • 7. Mellin H, Friesland S, Lowensohn R, Dalianis T, Munck-Wikland E. Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int. J. Cancer 89(3), 300–304 (2000).
    • 8. Gillison ML, Koch WM, Capone RB et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J. Natl Cancer Inst. 92(9), 709–720 (2000).
    • 9. Westra WH. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 3(1), 78–81 (2009).
    • 10. Liggett WH, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J. Clin. Oncol. 16(3), 1197–1206 (1998).
    • 11. Munger K, Baldwin A, Edwards KM et al. Mechanisms of human papillomavirus-induced oncogenesis. J. Virol. 78(21), 11451–11460 (2004).
    • 12. Goodman MT, Saraiya M, Thompson TD et al. Human papillomavirus genotype and oropharynx cancer survival in the United States. Eur. J. Cancer 51(18), 2759–2767 (2015).
    • 13. Preuss SF, Weinell A, Molitor M et al. Nuclear surviving expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer. Br. J. Cancer 98(3), 627–632 (2008).
    • 14. O'Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA. Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Onc. 48(12), 1191–1201 (2012).
    • 15. Amin MB, Edge S, Greene F et al. American Joint Committee on Cancer. In: AJCC Cancer Staging Manual (8th Edition). Springer International Publishing, NY, USA (2018).
    • 16. Marur S, Li S, Cmelak AJ et al. E1308: phase II trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx. J. Clin. Onc. 35(5), 490–497 (2017).
    • 17. Misiukiewicz K, Gupta V, Miles BA et al. Standard of care vs reduced-dose chemoradiation after induction chemotherapy in HPV+ oropharyngeal carcinoma patients. Oral Onc. 93(1), 170–177 (2019).
    • 18. Misiukiewicz K, Camille N, Gupta V et al. The role of HPV status in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin. Adv. Hematol. Oncol. 12(12), 812–819 (2014).
    • 19. Muller S, Khuri FR, Kono SA, Beitler JJ, Shin DM, Saba NF. HPV positive squamous cell carcinoma of the oropharynx. Are we observing an unusual pattern of metastases? Head Neck Pathol. 6(3), 336–344 (2012).
    • 20. Trosman SJ, Koyfman SA, Ward MC et al. Effect of human papillomavirus on patterns of distant metastatic failure in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy. JAMA Otolaryngol. Head Neck Surg. 141(5), 457–462 (2015). • Retrospective study which reveals differences in metastatic failure between patients with human papilloma virus (HPV)-positive and -negative primary tumors.
    • 21. Masroor F, Corpman D, Carpenter DM, Weintraub MR, Cheung KHN, Wang KH. Association of NCCN-recommended posttreatment surveillance with outcomes in patients with HPV-associated oropharyngeal squamous cell carcinoma. JAMA Otolaryngol. Head Neck Surg. 145(10), 903–908 (2019).
    • 22. Geurts TW, Nederlof PM, van den Brekel WM et al. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: metastasis or second primary? Clin. Cancer Res. 11(18), 6608–6614 (2005).
    • 23. Fakhry C, Westra WH, Cmelak A et al. Improved survival of patient with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J. Natl Cancer Int. 100(4), 261–269 (2008).
    • 24. Sinha P, Thorstad WT, Nussenbaum B et al. Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: a critical analysis of patterns and outcomes. Oral Oncol. 50(1), 45–51 (2014).
    • 25. Morris LGT, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J. Clin. Oncol. 29(6), 739–746 (2011). • SEER analysis which shows decreased rate of second primary malignancies in the head, neck and lung in patients with HPV-positive primary tumors.
    • 26. Xu C, Biron VL, Puttagunta L, Seikaly H. HPV status and second primary tumours in oropharyngeal squamous cell carcinoma. J. Otolaryngol. Head Neck Surg. 439(1), 1–6 (2013).
    • 27. Adjei BE, Buchanan P, Hinyard L, Osazuwa-Peters N, Schootman M, Piccirillo JF. Incidence and risk of second primary malignant neoplasm after a first head and neck squamous cell carcinoma. JAMA Otolaryngol. Head Neck Surg. 144(8), 727–737 (2018).
    • 28. Peck BW, Dahlstrom KR, Gan SJ et al. Low risk of second primary malignancies among never smokers with human papillomavirus-associated index oropharyngeal cancers. Head Neck 35(6), 794 (2013).
    • 29. Lee DH, Roh JL, Baek S et al. Second cancer incidence, risk factor, and specific mortality in head and neck squamous cell carcinoma. Otolaryngol. Head Neck Surg. 149(4), 579–586 (2013).
    • 30. Diaz DA, Reis IM, Weed DT, Elsayyad N, Samuels M, Abramowitz MC. Head and neck second primary cancer rates in the human papillomavirus era: a population-based analysis. Head Neck 38(Suppl. 1), E873–E883 (2016).
    • 31. Suk R, Mahale P, Sonawane K et al. Trends in risks for second primary cancers associated with index human papillomavirus-associated cancers. JAMA Netw. Open 1(1), 1–13 (2018).
    • 32. Hemminki K, Dong C, Vaittinen P. Second primary cancer after in situ and invasive cervical cancer. Epidemiology 11(4), 457–461 (2000). • Population study in Sweden which reports second primary malignancies in patients with HPV-associated cervical cancer.
    • 33. Teng CJ, Huon LK, Hu YW et al. Secondary primary malignancy risk in patients with cervical cancer in Taiwan. Medicine (Baltimore) 94(43), e1803 (2015).
    • 34. Berfeldt K, Einhorn S, Rosendahl I, Hall P. Increased risk of second primary malignancies in patients with gynecological cancer. A Swedish record-linkage study. Acta Oncol. 34(6), 771–777 (1995).
    • 35. Clifford GM, Franceschi S, Keiser O et al. Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: a nested case-control study in the Swiss HIV cohort study. Int. J. Cancer 138(7), 1732–1740 (2016).
    • 36. Hu G, Wu P, Cheng P et al. Tumor-infiltrating CD39 Tregs are novel immunosuppressive T cells in human colorectal cancer. J. Oncoimmunol. 6(2), 2 (2017).
    • 37. Wittke F, Hoffmann R, Buer J et al. Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma. Br. J. Cancer 79(12), 1182–1184 (1999).
    • 38. Glover MT, Deeks JJ, Raftery MJ, Cunningham J, Leigh IM. Immunosuppression and risk of non-melanoma skin cancer in renal transplant recipients. Lancet 349(9049), 398 (1997). • Looks at increased risk of melanoma in the setting of immunosuppression.
    • 39. Oguejiofor K, Galletta-Williams H, Dovedi SJ, Roberts DL, Stern PL, West CML. Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV – oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic. Oncotarget 8(9), 14416–14427 (2017).
    • 40. Lechien JR, Seminerio I, Descamps G et al. Impact of HPV infection on the immune system in oropharyngeal and non-oropharyngeal squamous cell carcinoma: a systematic review. Cells 8(9), 1061 (2019).