Squamous Cell Carcinoma of the Vulva in Brazil: Prognostic Importance of Host and Viral Variables

Pinto, Álvaro P.; Signorello, Lisa B.; Crum, Christopher P.; Harlow, Bernard L.; Abräo, Fauzer Simäo; Villa, Luisa L.

doi:10.1006/gyno.1999.5458

Cited by 51 publications

(38 citation statements)

References 27 publications

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“…This result is in agreement with previous studies that used different analytical techniques and demonstrated either no or only low prevalence of mucosal HPVs in these tumors. [4][5][6]12,13 Interestingly, two of four verrucous carcinomas in our study were found to be positive for HPV6. Since HPV6 is a low oncogenic risk HPV type, lesions caused by this HPV are not expected to show overexpression of p16…”

Section: Discussionmentioning

confidence: 60%

“…12,13,15,54 The reasons for this apparent lack of correlation in some cases may be multifold: (1) the presence of mixed morphologic features in the different areas of the tumor, resulting in imprecise classification (eg presence of keratin pearls in basaloid carcinoma, presence of pseudokoilocytes or inconspicuous keratin pearls in keratinizing carcinoma); (2) detection of 'passenger HPV' resulting in non-correlating positive result of HPV detection and negative result of p16 INK4a staining; (3) failure of HPV DNA amplification resulting in noncorrelating negative result of HPV detection and positive result of p16 INK4a staining; (4) additionally, a recent study from our laboratory showed that false-positive interpretive error of 'blush' p16 INK4a immunostaining could result in a lack of correlation with detection of high oncogenic risk HPVs in cervical mucosa. 55 The overlapping histologic features in different tumor subtypes were analyzed in detail in a recent study by Santos et al 13 In the series of vulvar carcinomas described by Santos et al, keratin pearls were identified in over a half of basaloid carcinomas and in all warty and keratinizing carcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…While testing for cutaneous HPVs in keratinizing and verrucous vulvar squamous cell carcinomas has not been reported previously, these tumor subtypes have been previously tested for mucosal HPVs showing either absence or low prevalence of HPV DNA. [4][5][6]12,13 Some studies report the presence of HPV6 and HPV11 in rare cases of verrucous carcinoma. 31,32 Since keratinizing and verrucous vulvar squamous cell carcinomas have never been evaluated for the presence of cutaneous HPVs, the first goal of our study was to test these tumors for the presence of cutaneous HPV types from the beta genus 33 and for mucosal HPVs using the SPF 10 -LiPA 25 system detecting 25 low and high oncogenic risk mucosal HPVs.…”

Section: Ink4amentioning

confidence: 99%

“…[4][5][6][8][9][10][11][12][13] Vulvar carcinomas not associated with mucosal HPVs occur in older women. These well-differentiated keratinizing squamous cell carcinomas histologically resemble conventional squamous cell carcinomas occurring in non-genital skin.…”

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Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

2008

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Two independent pathways of vulvar carcinogenesis have currently been identified, one related to infection with mucosal human papillomaviruses (HPVs) and a second related to chronic inflammatory or autoimmune processes. The goal of the study was to examine a possible role of cutaneous HPVs from the beta genus in vulvar carcinogenesis and to evaluate the distribution of intratypic variants of HPV 16 in HPV 16-positive vulvar cancer. Consecutive cases of vulvar carcinoma were retrieved from the files and included the following histologic subtypes: keratinizing (n ¼ 21), basaloid (n ¼ 7), warty (n ¼ 1), mixed basaloid-warty (n ¼ 4), verrucous (n ¼ 4), keratoacanthoma (n ¼ 1), basal cell carcinoma (n ¼ 1). All tumors were microdissected and tested for 25 beta HPV types and 25 mucosal HPV types. Cases identified as positive for HPV 16 were further tested for intratypic variants. All cases were immunostained for p16 INK4a . Beta HPVs were not detected in any of the tumor cases. Mucosal HPVs were detected in all but one basaloid/warty carcinomas; of these, nine cases (82%) were positive for HPV 16, including five European subtypes, one African subtype, one North American subtype and two indeterminate subtypes. Two of four verrucous carcinomas were positive for HPV 6. Mucosal HPVs were not detected in keratinizing carcinomas, keratoacanthoma and basal cell carcinoma. All cases of basaloid/warty carcinomas, but none of the remaining tumors, overexpressed p16 The pathogenesis of vulvar carcinoma is not entirely understood. Results of epidemiologic, clinicopathologic and virologic studies are in support of two independent pathways of vulvar carcinogenesis, one related to infection with oncogenic mucosal human papillomaviruses (HPVs) and a second related to a chronic inflammatory and/or autoimmune process involving vulvar mucosa and skin. [1][2][3][4][5][6] Vulvar cancers associated with oncogenic mucosal HPVs tend to occur in young women with past history of genital warts, cervical dysplasia and/or immunosuppression. These carcinomas typically belong to basaloid or warty histologic subtypes and develop from a well-characterized in situ lesion, namely, classic vulvar intraepithelial neoplasia grade 3 (VIN3).7 Approximately 80-90% of HPVpositive vulvar cancers are associated with HPV16 and nearly all remaining tumors are positive for HPV18 and HPV33. [4][5][6][8][9][10][11][12][13] Vulvar carcinomas not associated with mucosal HPVs occur in older women. These well-differentiated keratinizing squamous cell carcinomas histologically resemble conventional squamous cell carcinomas occurring in non-genital skin. 4 However, unlike the usual squamous cell carcinomas, vulvar cancers are not arising in the setting of actinic keratosis. In the vulva, these tumors develop in a background of squamous cell hyperplasia, a chronic inflammatory condition, or long-lasting lichen sclerosus, a lesion with strong links to autoimmune diseases. Although patients with lichen sclerosus

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Ink4amentioning

confidence: 99%

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confidence: 99%

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Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

2008

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“…4,5 Another complication is that various studies performed on head and neck and vulvar SCCs revealed a survival benefit for patients with a HPV-positive tumor, [8][9][10][11][12] whereas others failed to do so. [13][14][15] Also for penile SCC, 2 studies have been performed in which survival was correlated with the HPV-status of the primary tumor.These studies did not show survival differences between HPVpositive and HPV-negative tumors. 16,17 One of the possible explanations for the apparent discrepancies both in HPV prevalence rates and survival deals with the fact that sole HPV DNA detection might not be sufficient evidence of causation.…”

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Presence of high‐risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival

Lont

Kroon

Horenblas

et al. 2006

Intl Journal of Cancer

222

111

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There is evidence that a subset of penile carcinomas is caused by infection with high-risk human papillomavirus (HPV). However, extensive studies on the possible influence of HPV infection on clinical outcome of penile cancer are lacking. This investigation is aimed to examine the prevalence of high-risk HPV in a large series of penile squamous-cell carcinomas (SCCs) and to determine the relationship between HPV and survival. Formalin-fixed, paraffinembedded tumor specimens of 171 patients with penile carcinoma were tested for high-risk HPV DNA presence by GP51/61-PCR. The clinical course of the patients and the histopathological characteristics of the primary tumors were reviewed. High-risk HPV DNA was detected in 29% of the tumors, with HPV 16 being the predominant type, accounting for 76% of high-risk HPV containing SCCs. Disease-specific 5-year survival in the high-risk HPVnegative group and high-risk HPV-positive group was 78% and 93%, respectively (log rank test p 5 0.03). In multivariate analysis, the HPV status was an independent predictor for disease-specific mortality (p 5 0.01) with a hazard ratio of 0.14 (95% CI: 0.03-0.63). Our results indicate that the presence of high-risk HPV (29%) confers a survival advantage in patients with penile carcinoma. ' 2006 Wiley-Liss, Inc.Key words: penile carcinoma; HPV; survival Squamous-cell carcinoma (SCC) of the penis is uncommon and accounts for less than 1% of adult male cancers in developed countries. The incidence in Europe is 1 per 100,000 per year. 1 The highest incidence occurs in the seventh decade. The development is most likely a stepwise chain of events over a period of years from preneoplastic lesions to SCC. The etiology of penile SCC appears to be multifactorial, with a history of smoking, phimosis and poor hygiene are commonly associated with this tumor. 2,3 Recent data have also provided corroborative evidence for a role of high-risk human papillomavirus (HPV) in the pathogenesis of a subset of penile SCC. 4,5 These high-risk HPVs are known to possess transforming capacity and are a necessary but insufficient cause of cervical SCC. 6,7 More recently, also a role of these viruses has been implicated in the development of other SCCs, such as those of the head and neck and vulva, next to penile SCCs. In contrast to cervical cancers, almost all of which contain highrisk HPV, the reported high-risk HPV prevalence in the other mentioned SCCs is much lower. This suggests that the other SCCs are etiologically heterogeneous, with only a subset of cases linked to high-risk HPV. However, the exact proportion of these noncervical cancers that can be attributed to high-risk HPV is still a matter of debate since reported prevalence rates are highly variable, possibly as a result of the different testing methods that have been applied. Moreover, for penile carcinomas the histological subtype seems to be a determinant for HPV presence. Nevertheless, keratinizing or not-otherwise-specified penile SCCs, which represent the most common penile SCCs, generally show a...

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Vulvar Cancer

Benedet¹,

Ehlen²

2014

TNM Online

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Vulvar cancer is an uncommon malignancy accounting for approximately 4–5% of all gynecologic cancers. It used to be thought of as predominantly a disease of the elderly, although reports of young, reproductive‐age‐group women with this disease increasingly appear in the literature. The external location of the vulva should prompt early presentation, but traditionally significant delays in diagnosis have been associated with this cancer. The past decade has seen a better understanding of the prognostic factors for vulvar cancer, which, in turn, has led to a more individualized approach to therapy. This has led to less aggressive surgery in the earlier stage of the disease with better cosmetic and functional results. It might be expected that, with the increasing life expectancy in many countries and the concomitant aging of the population, an increase in the number of cases being diagnosed would occur in the future.

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Squamous Cell Carcinoma of the Vulva in Brazil: Prognostic Importance of Host and Viral Variables

Cited by 51 publications

References 27 publications

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma

Presence of high‐risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival

Vulvar Cancer

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