Prognosis of HPV-Positive and -Negative Oropharyngeal Cancers Depends on the Treatment Modality

Česká verzia

Authors: Z. Horáková ¹ ; M. Slavik ²; K. Veselý ³; M. Budíková ⁴ ; R. Kostřica ¹; H. Binková ¹
Authors place of work: Klinika otorinolaryngologie a chirurgie hlavy a krku LF MU a FN u svaté Anny v Brně ¹; Klinika radiační onkologie LF MU a Masarykův onkologický ústav, Brno ²; I. patologicko-anatomický ústav, LF MU a FN u svaté Anny v Brně ³; Ústav matematiky a statistiky, PřF MU, Brno ⁴
Published in the journal: Klin Onkol 2019; 32(3): 187-196
Category: Original Articles

Summary

Background: The association between human papilloma virus (HPV) and oropharyngeal carcinoma is a topical issue due mainly to the rapid increase in incidence over recent years. These tumors are etiopathogenetically, epidemiologically, and clinically different from other carcinomas at this location. They have a better prognosis in that they are more chemo-and radiosensitive. Indeed, this has been shown by many extensive retrospective and prospective studies. HPV status is considered an integral part of a standard histopathological examination and is included as a new biological parameter in TNM classification.

Materials and methods: The results of 77 patients who were treated non-surgically for locally advanced oropharyngeal carcinoma at a single university ear, nose, and throat clinic were analyzed retrospectively.

Results: Overall and specific survival of those with HPV-positive (HPV+) tumors was better that those for HPV negative (HPV-) tumors. With the exception of TNM classification, HPV positivity appeared to be the strongest predictor of local control, and of overall and specific survival, regardless of the type of treatment. However, smoking and p53 positivity were significant negative predictors of overall survival. Patients with HPV-associated tumors had a significantly better prognosis, regardless of treatment type. The difference between treatment modalities was confirmed for the whole group of patients, but not for the HPV+ and HPV-patients specifically, most probably due to the small number of patients enrolled.

Conclusion: The results obtained herein may constitute the first step toward the concept of treatment de-escalation in those with HPV-associated oropharyngeal carcinoma; however, this decision can be based only on the results of current extensive randomized trials. Specification of the optimal de-escalation scheme, or the choice of treatment modality, for which the difference in treatment results is most pronounced, has yet to be identified.

This work was supported by grants of the Ministry of Health of the Czech Republic IGA NT12483-4/2011 and AZV 15-31627A.

he authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 21. 9. 2018

Accepted: 14. 5. 2019

Keywords:

Oropharynx – cancer – HPV

Zdroje

1. Chaturvedi AK, Anderson WF, Lortet-Tieulent J et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol; 31 (36): 4550–4559. doi: 10.1200/JCO.2013.50.3870.

2. Dušek L, Mužík J, Kubásek M et al. Epidemiologie zhoubných nádorů v České republice. [online]. Dostupné z: http: //www.svod.cz/analyse.

3. Chaturvedi AK, Engels EA, Pfeiffer RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29 (32): 4294–4301. doi: 10.1200/JCO.2011.36.4596.

4. Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol 2006; 24 (17): 2606–2611. doi: 10.1200/JCO.2006.06.1291.

5. TNM Klasifikace zhoubných novotvarů. 8. vyd. Česká republika 2018.

6. Parkin DM, Bray F, Ferlay J et al. Global cancer statistics 2002. CA Cancer J Clin 2005; 55 (2): 74–108.

7. Smith E, Justine M. Ritchie et al. Human papillomavirus in oral exfoliated cells and risk of head and neck cancer head and neck cancer. J Natl Cancer Inst 2004; 96 (6): 449–455. doi: 10.1093/jnci/djh074.

8. Chaturvedi AK, Engels EA, Pfeiffer RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011; 29 (32): 4294–301. doi: 10.1200/JCO.2011.36.4596.

9. Hammarstedt L, Lindquist D, Dahlstrand H et al. Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int Jour Cancer 2006; 119 (11): 2620–2623. doi: 10.1002/ijc.22177.

10. Ernster JA, Sciotto CG, O’Brien MM et al. Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. Laryngoscope 2007; 117 (12): 2115–2128. doi: 10.1097/MLG.0b013e31813e5fbb.

11. Rotnáglová E, Tachezy R, Saláková M et al. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer 2011; 129 (1): 101–110. doi: 10.1002/ijc.25889.

12. Golusiński P, Pazdrowski J, Szewczyk M et al. Is immunohistochemical evaluation of p16 in oropharyngeal cancer enough to predict the HPV positivity? Rep Pract Oncol Radiother 2017; 22 (3): 237–242. doi: 10.1016/j.rpor.2017.01.003.

13. Rischin D, Young RJ, Fischer R et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 2010; 28 (27): 4142–4148. doi: 10.1200/JCO.2010.29.2904.

14. Chaturvedi AK, Engels EA, Anderson WF et al. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008; 26 (4): 612–619. doi: 10.1200/JCO.2007.14.1713.

15. Wilczynski SP, Lin BT, Xie Y et al. Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma. Am J Pathol 1998; 152 (1): 145–156.

16. Pytynia K, Dahlstrom KR, Sturgis EM. Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol 2014; 50 (5): 380–386. doi: 10.1016/j.oraloncology.2013.12.019.

17. Ang KK, Harris J, Wheeler R et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363 (1): 24–35. doi: 10.1056/NEJM-oa0912217.

18. Dai M, Clifford GM, le Calvez F et al. Human papillomavirus type 16 and TP53 mutation in oral cancer: matched analysis of the IARC multicenter study. Cancer Res 2004; 64 (2): 468–471.

19. Spanos WC, Nowicki P, Lee DW et al. Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg 2009; 135 (11): 1137–1146. doi: 10.1001/archoto.2009.159.

20. Gillison ML, D’Souza G, Westra W 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 (6): 407–420. doi: 10.1093/jnci/djn025.

21. Smith EM, Rubenstein LM, Haugen TH et al. Tobacco and alcohol use increases the risk of both HPV-associated and HPV-independent head and neck cancers. Cancer Causes Control 2010; 21 (9): 1369–1378. doi: 10.1007/s10552-010-9564-z.

22. Hafkamp HC, Manni JJ, Haesevoets A et al. Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer 2008; 122 (12): 2656–2664. doi: 10.1002/ijc.23 458.

23. Maxwell JH, Kumar B, Feng FY. Tobacco use in HPV-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res 2010; 16 (4): 1226–1235.

24. Mirghani H, Blanchard P. Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand? Clin Transl Radiat Oncol 2017; 8: 4–11. doi: 10.1016/ j.ctro.2017.10.005.

25. Orlandi E, Licitra L. Personalized medicine and the contradictions and limits of first-generation deescalation trials in patients with human papillomavirus–positive oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg 2018; 144 (2): 99–100. doi: 10.1001/jamaoto.2017.2308.

26. Masterson L, Moualed D, Masood A et al. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma. Cochrane Database Syst Rev 2014; (2): CD010271. doi: 10.1002/14651858.CD010271.pub2.

27. Tandon S, Tudur-Smith C, Riley RD et al. A systematic review of p53 as a prognostic factor of survival in squamous cell carcinoma of the four main anatomical subsites of the head and neck. Cancer Epidemiol Biomarkers Prev 2010; 19 (2): 574–587. doi: 10.1158/1055-9965.EPI-09-0981.

28. Maruyama H, Yasui T, Ishikawa-Fujiwara T et al. Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Sci 2014; 105 (4): 409–417. doi: 10.1111/cas. 12369.

29. Wittekindt C, Klussmann JP. Tumor staging and HPV-related oropharyngeal cancer. Recent Results Cancer Res 2017; 206: 123–133. doi: 10.1007/978-3-319-435 80-0_9.

30. Horne ZD, Glaser SM, Vargo JA et al. Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas. Cancer 2016; 122 (13): 2021–2030. doi: 10.1002/cncr.30021.