Skip to main content
Erschienen in: International Journal of Clinical Oncology 6/2019

29.01.2019 | Original Article

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma

verfasst von: Yoshifumi Yamamoto, Norihiko Takemoto, Takahiro Michiba, Yuji Seo, Fumiaki Isohashi, Keisuke Otani, Motoyuki Suzuki, Takashi Fujii, Tadashi Yoshii, Kenji Mitani, Toshimichi Yasui, Hironori Cho, Yasuhiko Tomita, Eiichi Morii, Teruki Teshima, Kazuhiko Ogawa, Hidenori Inohara

Erschienen in: International Journal of Clinical Oncology | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown.

Methods

We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox’s proportional hazard model.

Results

Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality.

Conclusions

Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
2.
Zurück zum Zitat Robinson M, Sloan P, Shaw R (2010) Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol 46:492–496CrossRefPubMed Robinson M, Sloan P, Shaw R (2010) Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing. Oral Oncol 46:492–496CrossRefPubMed
3.
Zurück zum Zitat Wiest T, Schwarz E, Enders C et al (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21:1510–1517CrossRefPubMed Wiest T, Schwarz E, Enders C et al (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21:1510–1517CrossRefPubMed
4.
Zurück zum Zitat Smeets SJ, Hesselink AT, Speel EJ et al (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472CrossRefPubMed Smeets SJ, Hesselink AT, Speel EJ et al (2007) A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 121:2465–2472CrossRefPubMed
5.
Zurück zum Zitat Rietbergen MM, Snijders PJ, Beekzada D et al (2014) Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas. Int J Cancer 134:2366–2372CrossRefPubMed Rietbergen MM, Snijders PJ, Beekzada D et al (2014) Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas. Int J Cancer 134:2366–2372CrossRefPubMed
6.
Zurück zum Zitat Fakhry C, Westra WH, Li S 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 100:261–269CrossRefPubMed Fakhry C, Westra WH, Li S 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 100:261–269CrossRefPubMed
7.
8.
Zurück zum Zitat Rischin D, Young RJ, Fisher R et al (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 28:4142–4148CrossRefPubMedPubMedCentral Rischin D, Young RJ, Fisher R et al (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol 28:4142–4148CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Machtay M, Moughan J, Trotti A et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589CrossRefPubMedPubMedCentral Machtay M, Moughan J, Trotti A et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Bhatia A, Burtness B (2015) Human Papillomavirus-associated oropharyngeal cancer: defining risk groups and clinical trials. J Clin Oncol 33:3243–3250CrossRefPubMedPubMedCentral Bhatia A, Burtness B (2015) Human Papillomavirus-associated oropharyngeal cancer: defining risk groups and clinical trials. J Clin Oncol 33:3243–3250CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Albers AE, Qian X, Kaufmann AM et al (2017) Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype. Sci Rep 7:16715CrossRefPubMedPubMedCentral Albers AE, Qian X, Kaufmann AM et al (2017) Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype. Sci Rep 7:16715CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Inohara H, Takenaka Y, Yoshii T et al (2015) Phase 2 study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III-IV squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91:934–941CrossRefPubMed Inohara H, Takenaka Y, Yoshii T et al (2015) Phase 2 study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III-IV squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91:934–941CrossRefPubMed
13.
Zurück zum Zitat Sobin L, Gospodarowicz M, Wittekind C (eds) (2010) UICC TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Chichester Sobin L, Gospodarowicz M, Wittekind C (eds) (2010) UICC TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Chichester
14.
Zurück zum Zitat Fuessel Haws AL, He Q, Rady PL et al (2004) Nested PCR with the PGMY09/11 and GP5+/6+ primer sets improves detection of HPV DNA in cervical samples. J Virol Methods 122:87–93CrossRefPubMed Fuessel Haws AL, He Q, Rady PL et al (2004) Nested PCR with the PGMY09/11 and GP5+/6+ primer sets improves detection of HPV DNA in cervical samples. J Virol Methods 122:87–93CrossRefPubMed
15.
Zurück zum Zitat Chang JT1, Kuo TF, Chen YJ et al (2010) Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther 17:827–836CrossRefPubMedPubMedCentral Chang JT1, Kuo TF, Chen YJ et al (2010) Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther 17:827–836CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Hu Z, Zhu D, Wang W et al (2015) Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet 47:158–163CrossRefPubMed Hu Z, Zhu D, Wang W et al (2015) Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism. Nat Genet 47:158–163CrossRefPubMed
17.
Zurück zum Zitat Maruyama H, Yasui T, Ishikawa-Fujiwara T et al (2014) Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Sci 105:409–417CrossRefPubMedPubMedCentral Maruyama H, Yasui T, Ishikawa-Fujiwara T et al (2014) Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Sci 105:409–417CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Nauta IH, Rietbergen MM, van Bokhoven AAJD et al (2018) Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing. Ann Oncol 29:1273–1279CrossRefPubMed Nauta IH, Rietbergen MM, van Bokhoven AAJD et al (2018) Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing. Ann Oncol 29:1273–1279CrossRefPubMed
19.
Zurück zum Zitat O’Sullivan B, Huang SH, Perez-Ordonez B et al (2012) Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol 103:49–56CrossRefPubMed O’Sullivan B, Huang SH, Perez-Ordonez B et al (2012) Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol 103:49–56CrossRefPubMed
20.
Zurück zum Zitat Rosenthal DI, Harari PM, Giralt J et al (2016) Association of human papillomavirus and p16 status with outcomes in the IMCL-9815 phase III registration trial for patients with locoregionally advanced oropharyngeal squamous cell carcinoma of the head and neck treated with radiotherapy with or without cetuximab. J Clin Oncol 34:1300–1308CrossRefPubMed Rosenthal DI, Harari PM, Giralt J et al (2016) Association of human papillomavirus and p16 status with outcomes in the IMCL-9815 phase III registration trial for patients with locoregionally advanced oropharyngeal squamous cell carcinoma of the head and neck treated with radiotherapy with or without cetuximab. J Clin Oncol 34:1300–1308CrossRefPubMed
21.
Zurück zum Zitat Rietbergen MM, Brakenhoff RH, Bloemena E et al (2013) Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials. Ann Oncol 24:2740–2745CrossRefPubMed Rietbergen MM, Brakenhoff RH, Bloemena E et al (2013) Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials. Ann Oncol 24:2740–2745CrossRefPubMed
22.
Zurück zum Zitat Pignon JP, Maitre AL, Maillard E et al (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomized trials and 17,346 patients. Radiother Oncol 92:4–14CrossRefPubMed Pignon JP, Maitre AL, Maillard E et al (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomized trials and 17,346 patients. Radiother Oncol 92:4–14CrossRefPubMed
Metadaten
Titel
Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma
verfasst von
Yoshifumi Yamamoto
Norihiko Takemoto
Takahiro Michiba
Yuji Seo
Fumiaki Isohashi
Keisuke Otani
Motoyuki Suzuki
Takashi Fujii
Tadashi Yoshii
Kenji Mitani
Toshimichi Yasui
Hironori Cho
Yasuhiko Tomita
Eiichi Morii
Teruki Teshima
Kazuhiko Ogawa
Hidenori Inohara
Publikationsdatum
29.01.2019
Verlag
Springer Singapore
Erschienen in
International Journal of Clinical Oncology / Ausgabe 6/2019
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01394-1

Weitere Artikel der Ausgabe 6/2019

International Journal of Clinical Oncology 6/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.