Clinical validation of methylation biomarkers for optimal detection of high‐grade vulvar intraepithelial neoplasia

Voss, Féline O; Thuijs, Nikki B.; Duin, Sylvia; Özer, Müjde; Beurden, Marc van; Berkhof, Johannes; Steenbergen, Renske D.M.; Bleeker, Maaike

doi:10.1002/ijc.34537

Cited by 6 publications

(2 citation statements)

References 34 publications

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“…In the complex field of carcinogenesis such as HPV‐independent vulvar carcinogenesis, the support of molecular genetics, which can definitely stratify the risk, seems now to be imperative. 33 …”

Section: Discussionmentioning

confidence: 99%

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

Gallio,

Preti,

Jones

et al. 2024

Acta Obstet Gynecol Scand

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IntroductionDifferentiated vulvar intraepithelial neoplasia (dVIN) is a high‐risk preinvasive vulvar lesion and precursor of human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN‐VSCC) at first diagnosis.Material and methodsA historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan–Meier method and log‐rank test were used to estimate cancer risk or recurrent cancer risk differences and uni‐ and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN‐VSCC.ResultsSeventy‐six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN‐VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5–128.0 months). VSCC recurrence absolute risk in treated dVIN‐VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5–94.8 months). At uni‐ and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN‐VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN‐VSCC patients on both uni‐ and multivariate regression analyses.ConclusionsPatients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long‐term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.

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Section: Discussionmentioning

confidence: 99%

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

Gallio,

Preti,

Jones

et al. 2024

Acta Obstet Gynecol Scand

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“…Additional complementary markers may prove to be highly valuable in aiding diagnosis of the various HPV-independent precursor subtypes. Promising alternative diagnostic biomarkers include IHC of CK17 and SOX2 as well as numerous DNA methylation markers that show particularly high levels in HPV-independent VIN, with a detection rate of 87% 22–25 …”

Section: Discussionmentioning

confidence: 99%

Incidence and Risk Factors for Recurrence and Progression of HPV–Independent Vulvar Intraepithelial Neoplasia

Voss,

van Beurden,

Veelders

et al. 2024

J Low Genit Tract Dis

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Objectives Human papillomavirus (HPV)–independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof. Materials and Methods Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga). Data were collected from the pathology reports. Crude and European age-standardized incidence rates were calculated for 10-year periods. Kaplan-Meier analyses were performed to determine the cumulative recurrence and cancer incidence, followed by Cox regression analyses to identify associated risk factors. Results A total of 114 patients were diagnosed with solitary HPV-independent VIN without prior or concurrent vulvar cancer. The European age-standardized incidence rate increased from 0.09 to 0.69 per 100,000 women-years between 1991–2010 and 2011–2019. A cumulative recurrence and cancer incidence of 29% and 46% were found after 8 and 13 years of follow-up, respectively. Nonradical surgery was identified as the only independent risk factor for recurrent HPV-independent VIN. Risk factors associated with progression to cancer were increasing age and a mutant p53 immunohistochemical staining pattern. Conclusions The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.

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DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

Voss,

Berkhof,

Duin

et al. 2024

Modern Pathology

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Clinical validation of methylation biomarkers for optimal detection of high‐grade vulvar intraepithelial neoplasia

Cited by 6 publications

References 34 publications

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

Differentiated vulvar intraepithelial neoplasia long‐term follow up and prognostic factors: An analysis of a large historical cohort

Incidence and Risk Factors for Recurrence and Progression of HPV–Independent Vulvar Intraepithelial Neoplasia

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

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