The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review

Voss, Féline O; Thuijs, Nikki B.; Vermeulen, R F M; Wilthagen, Erica A.; Beurden, Marc van; Bleeker, Maaike

doi:10.3390/cancers13246170

Cited by 17 publications

(26 citation statements)

References 32 publications

(80 reference statements)

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“…Unfortunately, the clinical behavior of these lesions is unknown. However, the appropriate classification of these lesions as HPV-independent might be clinically relevant in similarity with HPV-independent squamous premalignant lesions of the vulva which have proven to be more aggressive in the vulva 36. Thus, the patients with HSIL-like HPV-independent lesions of the penis will probably have to undergo a stricter follow-up than patients with penile HSIL.…”

Section: Discussionmentioning

confidence: 99%

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

Guerrero¹,

Trias²,

Veloza

et al. 2022

American Journal of Surgical Pathology

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Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPVassociated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPVassociated HSIL.

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Section: Discussionmentioning

confidence: 99%

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

Guerrero¹,

Trias²,

Veloza

et al. 2022

American Journal of Surgical Pathology

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“…If untreated, dVIN will progress to squamous cell carcinoma (SCC) more often than HSIL (50% versus 5.7%) [ 30 , 31 ]. The absolute risk for primary VSCC in dVIN varies between 33% and 86%, with the median time for progression of 9–23 months [ 32 ].…”

Section: Specific Features Of Vulvar Intraepithelial Neoplasiamentioning

confidence: 99%

Early Diagnostics of Vulvar Intraepithelial Neoplasia

Kesić

Vieira‐Baptista

Stockdale

2022

Cancers

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The spectrum of vulvar lesions ranges from infective and benign dermatologic conditions to vulvar precancer and invasive cancer. Distinction based on the characteristics of vulvar lesions is often not indicative of histology. Vulvoscopy is a useful tool in the examination of vulvar pathology. It is more complex than just colposcopic examination and presumes naked eye examination accompanied by magnification, when needed. Magnification can be achieved using a magnifying glass or a colposcope and may aid the evaluation when a premalignant or malignant lesion is suspected. It is a useful tool to establish the best location for biopsies, to plan excision, and to evaluate the entire lower genital system. Combining features of vulvar lesions can help prediction of its histological nature. Clinically, there are two distinct premalignant types of vulvar intraepithelial neoplasia: HPV-related VIN, more common in young women, multifocal and multicentric; VIN associated with vulvar dermatoses, more common in older women and usually unicentric. For definite diagnosis, a biopsy is required. In practice, the decision to perform a biopsy is often delayed due to a lack of symptoms at the early stages of the neoplastic disease. Clinical evaluation of all VIN lesions should be conducted very carefully, because an underlying early invasive squamous cancer may be present.

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“…Most markers showed significantly higher methylation levels in dVIN compared to vHSIL, which is consistent with the higher cancer risk in patients with dVIN. 6,7 Interestingly, a more heterogeneous methylation pattern was observed within the vHSIL group, likely reflecting a varying cancer risk. A previous study by our research group also identified SST as one of the best-performing methylation markers for cancer risk stratification in HPV-induced anal lesions.…”

Section: Discussionmentioning

confidence: 97%

“…[4][5][6] Patients with vHSIL and HPV-independent VIN have a varying risk of developing cancer, with a 10-year cumulative VSCC risk of 10% vs 50%, respectively. 6,7 Due to this risk, patients with vHSIL and HPV-independent VIN frequently undergo surgical interventions resulting in physical and psychosexual morbidity. 8 However, as only a minority of vHSIL patients develop cancer, prognostic biomarkers reflecting the cancer risk could reduce the necessity for mutilating overtreatment.…”

Section: Introductionmentioning

confidence: 99%

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

Voss

Thuijs

Duin

et al. 2023

Intl Journal of Cancer

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The precursor lesions of vulvar squamous cell carcinoma (VSCC) include human papillomavirus (HPV)-associated and HPV-independent squamous neoplasia with a varying cancer risk. Our study aimed to validate the accuracy of previously identified DNA methylation markers for detection of such high-grade vulvar intraepithelial neoplasia (VIN). A large clinical series of 751 vulvar lesions, originally diagnosed as high-grade VIN, were reassessed and categorized into HPV-associated or HPV-independent vulvar disease categories. Together with 113 healthy vulvar controls, all samples were tested for 12 methylation markers with quantitative multiplex methylation-specific PCR (qMSP). Performance of individual markers and selection of an optimal marker panel for detection of high-grade VIN was determined by logistic regression analysis.SST was the best-performing individual marker (AUC 0.90), detecting 80% of highgrade VIN cases, with excellent detection of HPV-independent VIN (95%), known to have the highest cancer risk. Merely 2% of controls tested methylation positive for SST. Selection of a marker panel, including ZNF582, SST and miR124-2, resulted in a comparably high accuracy for detection of high-grade VIN (AUC 0.89). In conclusion, we clinically validated the accuracy of 12 DNA methylation markers for detection of high-grade VIN. SST, as a sole marker or in a panel, provides an optimal diagnostic tool to distinguish high-grade VIN in need of treatment, particularly HPV-

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The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review

Cited by 17 publications

References 32 publications

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

HPV-negative Penile Intraepithelial Neoplasia (PeIN) With Basaloid Features

Early Diagnostics of Vulvar Intraepithelial Neoplasia

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

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