Vulvar Squamous Cell Carcinoma and Papillomaviruses: Indications for Two Different Etiologies

Hørding, Ulla; Junge, Jette; Daugaard, Søren; Lundvall, Finn; Poulsen, Hemming; Bock, Johannes E.

doi:10.1006/gyno.1994.1039

Cited by 134 publications

(95 citation statements)

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“…In general, several studies showed that patients with uVINrelated vulvar SCC are younger than dVIN/LS-related vulvar SCC patients (Hording et al, 1994;Hampl et al, 2006;Hoevenaars et al, 2008;van de Nieuwenhof et al, 2009a). In our study, we confirm this observation with a significant difference in age distribution between the two different groups, 72 years for the hrHPVunrelated and 54 years for the hrHPV-related groups (Po0.001).…”

Section: Discussionsupporting

confidence: 87%

“…Recently, we found that uVIN-associated vulvar SCC patients had a significantly better disease-free survival than dVIN-associated vulvar SCC patients (van de Nieuwenhof et al, 2009b). The majority of uVIN-related vulvar SCCs are caused by HPVs 16, 18 and 33 (Toki et al, 1991;Hording et al, 1994;Iwasawa et al, 1997;Pinto et al, 2004;Hampl et al, 2006). The development of uVIN and vulvar SCC mirrors that of cervical intraepithelial neoplasia (CIN) and cervical SCC, the latter caused by (high-risk human papillomavirus) hrHPV in nearly 100% of the cases (Walboomers et al, 1999;Bekkers et al, 2004).…”

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confidence: 99%

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Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

et al. 2009

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BACKGROUND: Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC. METHODS: All vulvar SCCs (201) were classified to be dVIN-(n ¼ 164) or uVIN related (n ¼ 37). Data with regard to the smear history and cervical histology were retrieved from PALGA, the nationwide Netherlands database of histo-and cytopathology. For HSIL cervical smears of which histology was taken, HPV DNA analysis on both the vulvar and cervical specimens was performed. RESULTS: At least one smear was available in 145 (72%) of the 201 patients. Patients with a uVIN-related vulvar SCC more often had an HSIL compared with patients with a dVIN-related SCC (35 vs 2%, Po0.001). A total of 10 of the 13 HSILs were histologically assessed and identical HPV types were found in the vulva and cervix. CONCLUSION: These data emphasise the necessity to differentiate between dVIN-and uVIN-related vulvar tumours and to examine the entire lower female ano-genital tract once an uVIN-related lesion is found.

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Section: Discussionsupporting

confidence: 87%

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confidence: 99%

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

et al. 2009

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“…We hypothesize that there are genes less frequent and studied that mediate VSCC. Thus, our study describes a new model that does not involve the preconceived etiogenic pathways that are linked exclusively to HPV infection or p53 disruption (2,33), because no gene was associated with either pathway in our analysis. In addition, low expression of both GNB3 and PLXDC2 in normal tissues might reflect their relevance in vulvar carcinogenesis and in tumor progression as they could reflect a suppression mechanism feedback, imposed by PLXDC2 and a tumoral enhancer promoted by GNB3 expression.…”

Section: Discussionmentioning

confidence: 99%

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

Lavorato-Rocha

Akagi

Maia

et al. 2016

Molecular Cancer Research

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Vulvar squamous cell carcinoma (VSCC) is a rare disease that has a high mortality rate ($40%). However, little is known about its molecular signature. Therefore, an integrated genomics approach, based on comparative genome hybridization (aCGH) and genome-wide expression (GWE) array, was performed to identify driver genes in VSCC. To achieve that, DNA and RNA were extracted from frozen VSCC clinical specimens and examined by aCGH and GWE array, respectively. On the basis of the integration of data using the CONEXIC algorithm, PLXDC2 and GNB3 were validated by RT-qPCR. The expression of these genes was then analyzed by IHC in a large set of formalin-fixed paraffin-embedded specimens. These analyses identified 47 putative drivers, 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in the same sample was significantly associated with less lymph node metastasis and greater disease-free survival. On the basis of a robust methodology never used before for VSCC evaluation, two novel prognostic markers in vulvar cancer are identified: one with favorable prognosis (GNB3) and the other with unfavorable prognosis (PLXDC2).Implications: This genomics study reveals markers that associate with prognosis and may provide guidance for better treatment in vulvar cancer.

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“…However, the majority of vulvar squamous cell carcinoma patients do not have a recorded and histopathologically proven history of lichen sclerosus, but suffer from lichen sclerosus, either asymptomatic or unnoticed. 4,28,[31][32][33] This may result in delayed diagnosis by both patients and doctors. In our vulvar clinic, the policy is to biopsy every woman with a suspicion of lichen sclerosus, because this diagnosis has the consequence of a lifelong follow-up (at least yearly).…”

Section: Discussionmentioning

confidence: 99%

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

et al. 2011

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Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n ¼ 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (Po0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P ¼ 0.004), dyskeratosis (Po0.001), hyperplasia (P ¼ 0.048) and basal cellular atypia (P ¼ 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.

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Vulvar Squamous Cell Carcinoma and Papillomaviruses: Indications for Two Different Etiologies

Cited by 134 publications

References 0 publications

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

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