Abstract
BackgroundTNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and -unrelated OPSCC based on p16INK4a overexpression (p16+), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16+ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite. Patients and methodsAll 932 patients, treated with curative intent in Stockholm 2000–2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively. ResultsPatients with p16+ otherOPSCC had significantly poorer OS compared to patients with p16+ TSCC/BOTSCC (p = 0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16+ otherOPSCC had a significant poorer OS compared to patients with p16+ TSCC/BOTSCC and similar stage (p = 0.02). Lastly, patients with otherOPSCC and low TNM-7 stage had a significant better OS, as compared to those with a high stage (p = 0.019) while no hazard discrimination was observed with TNM-7 in TSCC/BOTSCC. ConclusionOur results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.
Highlights
During the last decades the incidence of human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinomas (OPSCC) has increased epidemically in Sweden and many other western countries, while the incidence of HPV-unrelated OPSCC has remained stable [1e6]
P16 overexpression as well as HPV DNA were significantly more often observed in TSCC/BOTSCC as compared to otherOPSCC (76% p16þ TSCC/BOTSCC vs 14% p16þ otherOPSCC, p < 0.0001 and 76% HPV DNA positive TSCC/BOTSCC vs 22% HPV DNA positive otherOPSCC, p < 0.0001)
We show that patients with p16þ otherOPSCC and a low tumor stage according to the new TNM-8 staging system have a significant poorer survival as compared to patients with p16þ TSCC/
Summary
During the last decades the incidence of human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinomas (OPSCC) has increased epidemically in Sweden and many other western countries, while the incidence of HPV-unrelated OPSCC has remained stable [1e6]. Patients with HPV-mediated OPSCC are generally younger and present significantly more often with smaller primary tumors, and with more advanced regional disease as compared to patients with HPV-unrelated OPSCC. HPV-mediated and HPV-unrelated OPSCC are separated on the basis of p16 overexpression (p16þ) (as a surrogate marker for HPV) in the new 8th Ed. AJCC staging manual (TNM8) and staged . TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and -unrelated OPSCC based on p16INK4a overexpression (p16þ), as surrogate marker for HPV. OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). Patients with TNM-8 stage I-II and p16þ otherOPSCC had a significant poorer OS compared to patients with p16þ TSCC/BOTSCC
Sign-in/Register to view highlights & summary 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.
