Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy

Heiduschka, Gregor; Grah, Anja; Oberndorfer, Felicitas; Kadletz, Lorenz; Altorjai, Gabriela; Kornek, Gabriela; Wrba, Fritz; Thurnher, Dietmar

doi:10.1007/s00066-014-0753-7

Cited by 34 publications

(30 citation statements)

References 24 publications

(21 reference statements)

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“…Previously, we and others have shown that the HPV infection status is a strong prognosticator for locoregional control in patients with locally advanced HNSCC who received postoperative radio(chemo)therapy (6,28,29) with an improved locoregional control and radiosensitivity of HPV16 DNA positive in comparison with HPV16 DNA-negative tumors. In our previous multicenter evaluation, we found virtually no recurrences in the HPV16 DNA-positive group among high-risk HNSCC patients who received PORT-C (6).…”

Section: Discussionmentioning

confidence: 91%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

116

143

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Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

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Section: Discussionmentioning

confidence: 91%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

116

143

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“…Furthermore, because the better outcome of these patients [22,23], the risk of a radiation-induced second cancer must be taken in account.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Maxillary and mandible contouring in patients with a head and neck area irradiation

Rouers¹,

Antoni²,

Thompson

et al. 2016

Practical Radiation Oncology

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“…Table 2 indicates the number of patients belonging to the different subgroups depending on the HPV and p16-status. The proportion of the subgroups was estimated from the 16 studies, which explicitly indicated the patient number [11,15,25,26,34,36,43,47,48,58,62,68,69,75,80,82]. The subgroup of HPV ?…”

Section: Description Of the Included Studiesmentioning

confidence: 99%

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status

Coordes

Lenz

Qian

et al. 2015

Eur Arch Otorhinolaryngol

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Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV(+/-) and p16(+/-) status consistently found discordant results with p16(-)/HPV(+) and p16(+)/HPV(-). However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV(+/-) and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV(+)/p16(+), 61.2 % for HPV(-)/p16(-), 7.1 % for HPV(-)/p16(+) and 6.8 % for HPV(+)/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV(+)/p16(+) HNSCC in comparison to HPV(-)/p16(-), HPV(+)/p16(-) and HPV(-)/p16(+). The 5-year OS of the HPV(-)/p16(+) subgroup was intermediate while HPV(+)/p16(-) and HPV(-)/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV(+)/p16(+) or HPV(-)/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV(+)/p16(-) and HPV(-)/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable.

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Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy

Cited by 34 publications

References 24 publications

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Maxillary and mandible contouring in patients with a head and neck area irradiation

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status

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