Overexpression of p16INK4a serves as prognostic marker in squamous cell vulvar cancer patients treated with radiotherapy irrespective of HPV-status

• Verfasst von: Arians, Nathalie [VerfasserIn]
• Verfasst von: Prigge, Elena-Sophie [VerfasserIn]
• Verfasst von: Nachtigall-Schmitt, Tereza [VerfasserIn]
• Verfasst von: Reuschenbach, Miriam [VerfasserIn]
• Verfasst von: Debus, Jürgen [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Lindel, Katja [VerfasserIn]
• Titel: Overexpression of p16INK4a serves as prognostic marker in squamous cell vulvar cancer patients treated with radiotherapy irrespective of HPV-status
• Verf.angabe: Nathalie Arians, Elena-Sophie Prigge, Tereza Nachtigall, Miriam Reuschenbach, Stefan Alexander Koerber, Juergen Debus, Magnus von Knebel Doeberitz and Katja Lindel
• E-Jahr: 2019
• Jahr: 11 September 2019
• Umfang: 9 S.
• Fussnoten: Gesehen am 07.10.2019 ; Im Titel ist "INK4a" hochgestellt
• Titel Quelle: Enthalten in: Frontiers in oncology
• Ort Quelle: Lausanne : Frontiers Media, 2011
• Jahr Quelle: 2019
• Band/Heft Quelle: 9(2019) Artikel-Nummer 891, 9 Seiten
• ISSN Quelle: 2234-943X
• DOI: doi:10.3389/fonc.2019.00891
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Human papillomavirus (HPV)
• Sach-SW: p16 INK4A
• Sach-SW: Prognostic factor
• Sach-SW: Radiotherapy
• Sach-SW: Vulvar squamous cell carcinoma (VSCC)
• K10plus-PPN: 1678185825
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Purpose: We aimed to evaluate the impact of HPV-driven carcinogenesis on outcome in vulvar squamous cell carcinoma patients (VSCC) treated with radiotherapy. Methods and Materials: Analysis of clinical, pathological and treatment data, HPV DNA-detection and -genotyping as well as p16INK4a immunohistochemistry were performed in 75 VSCC patients. Kaplan-Meier-method was used to estimate locoregional control (LC), Progression-free survival (PFS) and Overall Survival (OS). Univariate survival time comparisons were performed using the log-rank-test. Chi-square/Fisher exact test was used to assess correlations between HPV DNA and p16INK4a data, pathological, clinical and treatment characteristics. Results: 23/75 (30.67%) of all women had locoregional relapse, 7/75 (9.3%) systemic recurrence and 35/75 (46.67%) died after a median follow-up of 26.4 months. 21.3% of the tumors were HPV DNA-positive, mostly (93.75%) for the high-risk (HR) HPV type 16. 25.3% showed p16INK4a-overexpression. 17.3% showed concomitant HPV DNA- and p16INK4a-positivity (cHPPVC). Patients with p16INK4a-overexpression, irrespective of the HPV DNA status, showed significantly better PFS (5-year-PFS 69.3% vs 39.2%, p=0.045), LC (5-year-LC 86.7% vs 56.7%, p=0.033) and a strong trend for better OS (5-year-OS 75.6% vs 43.9%, p=0.077). Patients with cHPPVC showed a trend for better PFS (5-year-PFS 72.7% vs 41.3%, p=0.082) and OS (5-year-OS 81.1% vs 45.7% , p=0.084) but no significant benefit for LC. Conclusions: Patients with cHPPVC, indicating an etiological relevance of HPV in the respective tumors, showed a better, albeit not significant, prognosis. The sole detection of p16INK4a-overexpression is a prognostic factor for survival in vulvar cancer and indicates better prognosis after radiotherapy, independent of detection of HPV DNA. p16INK4a should be used as surrogate marker for HPV-driven carcinogenesis in vulvar cancer with caution.