Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age

Nieuwenhof, H.P. van de; Massuger, Leon F.A.G.; Avoort, Irene A.M. van der; Bekkers, Ruud L.M.; Casparie, Mariël K.; Abma, Wim; Kempen, Léon C van; Hullu, Joanne A. de

doi:10.1016/j.ejca.2008.11.037

Cited by 168 publications

(174 citation statements)

References 24 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…[36][37][38][39][40] Notably, HPV-induced vulvar carcinomas are known for their good overall prognosis and survival rate of approximately 80%. 41,42 In the current study, the increased presence of single CD141 cells, representative for M1 macrophages, was related to a decreased RFS but so was the number of all intraepithelial CD141 cells, comprising both M1 and M2 macrophages. Most notably, in uVIN the increase in one myeloid cell population coincided with the increase in all other myeloid populations (Supporting Information Table S1) as well as with intraepithelial CD41 regulatory T cells.…”

Section: Discussionsupporting

confidence: 46%

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Esch

Poelgeest

Trimbos

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages. While the M2 macrophages outnumber M1 macrophages in healthy controls and uVIN, they are matched in number by M1 macrophages in cancer. Importantly, uVIN patients with a dense intraepithelial infiltration with mature CD141 macrophages (irrespective of M1 or M2 type) displayed approximately a six times higher risk to develop a recurrence and a high number of these cells constituted an independent prognostic factor for recurrence. In addition, a dense intraepithelial CD141 cell infiltration was associated with high numbers of intraepithelial CD41 Tregs and low numbers of stromal CD81TIM31 T cells. Patients with low numbers of intraepithelial CD141 cells and high numbers of stromal CD81TIM31 cells showed the best recurrence-free survival. These data clearly show the importance of the local immune response in HPV-induced vulvar neoplasia and may be of help in predicting the prognosis of patients or their response to immunotherapy.Usual-type vulvar intraepithelial neoplasia (uVIN) lesions are caused by a persistent high-risk human papilloma virus (HPV) infection (mainly HPV 16) and are characterized by high recurrences, a low spontaneous regression rate of 1.5% and a malignant potential of 3-4% in treated patients. [1][2][3] Treatment of uVIN lesions is indispensable since 80% of patients suffer from symptoms as pruritis and pain. 2-4 Conventional treatment consistent of potential disfiguring surgical interventions is associated with psychosexual problems and is increasingly replaced by either standardized immunotherapy with imiquimod or immunotherapy in experimental setting by therapeutic vaccination or photodynamic therapy, with promising clinical successes. [2][3][4][5][6][7][8] The incidence of hrHPV-induced dysplasia is increased in immunocompromised patients highlighting the essential role of the immune system in viral clearance. 9,10 Spontaneous regression of HPV is associated with systemic HPV-specific CD41 and CD81 immune responses, however in most of the patients with uVIN these T cell responses are either weak or absent. 11,12 In addition, the local innate immune cell environment is known to influence innate and adaptive immune responses in tumors. 13,14 Monocytes are innate immune cells which can differentiate into dendritic cells (DCs) or macrophages in response to local factors. 13 DCs process and present antigens to T cells, stimulate cytotoxicity of NK cells and initiate the adaptive immune response. 15 Studies of the microenvironment in uVIN revealed that ...

show abstract

Section: Discussionsupporting

confidence: 46%

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Esch

Poelgeest

Trimbos

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…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: 81%

“…This emphasises the concept that a patient with a hrHPV-related ano-genital (pre)malignancy is at a higher risk to develop another hrHPVrelated (pre)malignancy. We previously reported that 41% of uVIN patients had a past, simultaneous or future HPV-induced cervical, vaginal or anal lesion (van de Nieuwenhof et al, 2009a). Unfortunately, in this cohort of vulvar SCC patients, we were not able to retrieve data about other multicentric sites of the lower female ano-genital tract prone to hrHPV infection.…”

Section: Discussionmentioning

confidence: 65%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…The nuclear chromatin is vesicular rather than coarse, and the nuclei have prominent nucleoli (Figure 3e), usually most prominently in the basal and parabasal keratinocytes. 8 Although differentiated VIN is seen adjacent to B80% of vulvar squamous cell carcinomas, 2 it is seldom diagnosed as a solitary lesion, 10 which may be explained by underdiagnosis due to its difficult recognition [11][12][13] or due to its short intraepithelial phase. 10 It has been hypothesized that differentiated VIN may develop from lichen sclerosus and that it carries a higher malignant potential than lichen sclerosus does, 3,13-17 but its role as a premalignant lesion has not been accepted by all pathologists.…”

mentioning

confidence: 99%

“…8 Although differentiated VIN is seen adjacent to B80% of vulvar squamous cell carcinomas, 2 it is seldom diagnosed as a solitary lesion, 10 which may be explained by underdiagnosis due to its difficult recognition [11][12][13] or due to its short intraepithelial phase. 10 It has been hypothesized that differentiated VIN may develop from lichen sclerosus and that it carries a higher malignant potential than lichen sclerosus does, 3,13-17 but its role as a premalignant lesion has not been accepted by all pathologists. 18 We hypothesize that of all lesions that have been diagnosed as lichen sclerosus in the past, a substantial part might currently be diagnosed as differentiated VIN.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age

Cited by 168 publications

References 24 publications

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV‐induced vulvar neoplasia

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

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

Contact Info

Product

Resources

About