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
Vos, R.A.; Pasmans, H.; Tymchenko, L.; Janga-Jansen, A.V.A.; Baboe-Kalpoe, S.; Hulshof, K.; ... ; Klis, F.R.M. van der 2020
Background: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on... Show moreBackground: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017.Methods: Blood samples from participants (n = 1,823, 0-90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged >= 15 years who ever had sex (n = 1,080).Results: Among unvaccinated individuals aged >= 15 years, overall seropositivity was high (34%), with over half of them being seropositive for >= 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20-59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity.Conclusions: In accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program. (C) 2020 The Authors. Published by Elsevier Ltd. Show less
Poelgeest, M.I.E. van; Visconti, V.V.; Aghai, Z.; Ham, V.J. van; Heusinkveld, M.; Zandvliet, M.L.; ... ; Welters, M.J.P. 2016
Cutaneous warts are caused by the human papillomavirus (HPV). Although warts are one of the most common reasons to consult general practice, there is a considerable lack of evidence on the... Show moreCutaneous warts are caused by the human papillomavirus (HPV). Although warts are one of the most common reasons to consult general practice, there is a considerable lack of evidence on the transmission and treatment of warts. This thesis presents epidemiological data from a cohort of primary school children, and two pragmatic multicenter randomized trials on common treatments for warts in general practice. The results reveal that current recommendations on both prevention and treatment of warts should be revised. In addition, this thesis explores the clinical use of determining specific wart-associated HPV type. Show less
Cervical cancer is induced by HPV in virtually all cases, but it is still unknown how these virus-positive tumors arise in the face of immunity. In this thesis we examined the role of different... Show moreCervical cancer is induced by HPV in virtually all cases, but it is still unknown how these virus-positive tumors arise in the face of immunity. In this thesis we examined the role of different arms of the adaptive immune response on cervical cancer. In previous studies, it was shown that cancer patients do have a detectable immune response against the HPV16 E6 and E7 antigens. However, in general this response was not associated with cytokine production. In the present study, the mechanism underlying this dysfunctional immune response was investigated by studying the presence, specificity and function of the local T-cell response in patients with HPV-induced cervical malignancies at different stages of disease. Low CD8/Treg ratio is a significant independent unfavorable prognostic factor in cervical cancer patients. Frequently, the tumor is also infiltrated with HPV-specific CD4+ and CD8+ T-cells which can potentially attack the tumor. The infiltrating T-cells also include HPV-specific regulatory T-cells which are able to suppress the reactivity of neighboring T-cells. Their presence may explain the failure of the immune system to control HPV-induced tumors. Show less
