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... Show moreObjective. 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. Show less
The risk of cutaneous squamous cell carcinoma (cSCC) is highly increased in organ transplant recipients (OTR) and these tumours carry a major health burden for these patients. This thesis dealt... Show moreThe risk of cutaneous squamous cell carcinoma (cSCC) is highly increased in organ transplant recipients (OTR) and these tumours carry a major health burden for these patients. This thesis dealt with several aspects of cSCC in OTR. The chapters 2 and 3 review the role of HPV in cSCC and study HPV as a prognostic factor in the aetiology of cSCC. Subsequently, diagnostic factors were studied. In chapter 4 we intended to identify p16 as a possible histopathological marker for cSCC and in chapter 5 we studied the clinical implication of pain as a symptom to differentiate cSCC from other keratinocyte lesions. In chapter 6 we reviewed the literature on metastasis risk in immunocompetent versus OTR population. We studied in chapter 7 in our own population the risk for metastasis, and subsequently risk factors, of cSCC in OTR compared to immunocompetent patients. Show less
