TY - JOUR
T1 - Vulvar cancer subclassification by HPV and p53 status results in three clinically distinct subtypes
AU - Kortekaas, Kim E.
AU - Bastiaannet, Esther
AU - van Doorn, Helena C.
AU - van Steenwijk, Peggy J. de Vos
AU - Ewing-Graham, Patricia C.
AU - Creutzberg, Carien L.
AU - Akdeniz, Kadir
AU - Nooij, Linda S.
AU - van der Burg, Sjoerd H.
AU - Bosse, Tjalling
AU - van Poelgeest, Mariette I. E.
N1 - Funding Information:
KEK was financially supported by a grant from the Dutch Cancer Society ( 2016-10168 , to MIEvP, TB, and SHvdB).
Funding Information:
We would like to thank Enno Dreef, Natalja ter Haar and Isabelle Gordijn for their technical support, and Heleen Rogaar for her help with collecting the clinical data of the cohort. KEK was financially supported by a grant from the Dutch Cancer Society (2016-10168, to MIEvP, TB, and SHvdB).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/12
Y1 - 2020/12
N2 - 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 HPVnegative/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 p16and 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. (C) 2020 Elsevier Inc. All rights reserved.
AB - 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 HPVnegative/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 p16and 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. (C) 2020 Elsevier Inc. All rights reserved.
KW - Vulvar squamous cell carcinoma
KW - Human papillomavirus
KW - p53
KW - p16
KW - TP53
KW - Molecular classification
KW - Prognosis
KW - SQUAMOUS-CELL CARCINOMA
KW - HUMAN-PAPILLOMAVIRUS HPV
KW - RELATIVE SURVIVAL
KW - MANAGEMENT
KW - DISEASE
KW - TRENDS
KW - PROGNOSIS
KW - SEPARATE
KW - LESIONS
KW - RISK
U2 - 10.1016/j.ygyno.2020.09.024
DO - 10.1016/j.ygyno.2020.09.024
M3 - Article
C2 - 32972785
SN - 0090-8258
VL - 159
SP - 649
EP - 656
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -