Abstract
EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.
Highlights
Head and neck squamous cell carcinomas (HNSCC) is expected to account for approximately 740 000 new cases and 410 000 deaths worldwide, for the year 2015 [1]
A negative autoregulatory loop between p16 and pRb has been described [5] and degradation of pRb by Human papillomavirus (HPV) E7 oncoproteins leads to p16 upregulation in HPV(þ) cancers. p16 IHC followed by PCR for HPV DNA has been proposed as a reliable algorithm for detection of HPV in paraffin-embedded OPSCC specimens. p16 protein expression, is not a reliable surrogate marker for HPV infection outside the oropharynx
EORTC 24971 randomized 358 patients with primary inoperable nonmetastatic HNSCC between TPF chemotherapy and PF induction chemotherapy followed by radiotherapy and demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) with the addition of docetaxel to PF [9]
Summary
Head and neck squamous cell carcinomas (HNSCC) is expected to account for approximately 740 000 new cases and 410 000 deaths worldwide, for the year 2015 [1]. HPV DNA PCR is a sensitive but not a specific method for determination of HPV status. Immunohistochemistry (IHC) for p16 protein expression is used as a surrogate marker of HPV infection in OPSCC. P16 IHC followed by PCR for HPV DNA has been proposed as a reliable algorithm for detection of HPV in paraffin-embedded OPSCC specimens. HPV-DNAþ and/or p16þ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
