Kim E Kortekaas1, Esther Bastiaannet2, Helena C van Doorn3, Peggy J de Vos van Steenwijk4, Patricia C Ewing-Graham5, Carien L Creutzberg6, Kadir Akdeniz5, Linda S Nooij7, Sjoerd H van der Burg8, Tjalling Bosse9, Mariette I E van Poelgeest7. 1. Department of Gynecology, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, the Netherlands; Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, the Netherlands. Electronic address: k.e.kortekaas@lumc.nl. 2. Department of Surgery and Medical Oncology, Leiden University Medical Center, Leiden, PO Box 9600, 2300, RC Leiden, the Netherlands. 3. Department of Gynecology, ErasmusMC Cancer Institute, University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands. 4. Departement of Gynecology, Maastricht University Medical Center, PO Box 5800, 6202, AZ, Maastricht, the Netherlands. 5. Department of Pathology, ErasmusMC Cancer Institute, University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands. 6. Department of Radiation Oncology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, the Netherlands. 7. Department of Gynecology, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, the Netherlands. 8. Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, the Netherlands. 9. Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Leiden, the Netherlands.
Abstract
OBJECTIVE: There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations. METHODS: A large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPV-negative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models. RESULTS: Of the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80-6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48-10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02-7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002). CONCLUSIONS: Stratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials.
OBJECTIVE: There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations. METHODS: A large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPV-negative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models. RESULTS: Of the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80-6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48-10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02-7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002). CONCLUSIONS: Stratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials.
Authors: Kim E Kortekaas; Saskia J Santegoets; Liselotte Tas; Ilina Ehsan; Pornpimol Charoentong; Helena C van Doorn; Mariette I E van Poelgeest; Dana A M Mustafa; Sjoerd H van der Burg Journal: J Immunother Cancer Date: 2021-10 Impact factor: 13.751
Authors: Bertine W Huisman; Merve Cankat; Tjalling Bosse; Alexander L Vahrmeijer; Robert Rissmann; Jacobus Burggraaf; Cornelis F M Sier; Mariette I E van Poelgeest Journal: Cancers (Basel) Date: 2021-11-29 Impact factor: 6.639
Authors: Tynisha S Rafael; Jossie Rotman; Oscar R Brouwer; Henk G van der Poel; Constantijne H Mom; Gemma G Kenter; Tanja D de Gruijl; Ekaterina S Jordanova Journal: J Clin Med Date: 2022-02-19 Impact factor: 4.241