HPV status and favourable outcome in vulvar squamous cancer

Wakeham, Katie; Kavanagh, Kimberley; Cuschieri, Kate; Millan, David; Pollock, Kevin G; Bell, Sarah; Burton, Kevin; Reed, Nick; Graham, Sheila V.

doi:10.1002/ijc.30523

Cited by 60 publications

(61 citation statements)

References 30 publications

(36 reference statements)

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“…The majority of studies ( n = 15) used formalin‐fixed paraffin‐embedded tissue samples for diagnosis and HPV testing. Most studies ( n = 14) used polymerase chain reaction (PCR)‐based test to detect HPV DNA, while two studies used in situ hybridization (ISH) and one study used hybrid capture 2 (HC2). Finally, one study used p16 immunohistochemistry (p16 IHC) as a surrogate marker for HPV infection …”

Section: Resultsmentioning

confidence: 99%

Does HPV status influence survival after vulvar cancer?

Rasmussen

Sand

Frederiksen

et al. 2017

Intl Journal of Cancer

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High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I = 51%; DFS: I = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.

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Section: Resultsmentioning

confidence: 99%

Does HPV status influence survival after vulvar cancer?

Rasmussen

Sand

Frederiksen

et al. 2017

Intl Journal of Cancer

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“…Finally, the complete absence of clinical and follow‐up data prevents obtaining any conclusions on the prognostic implications of HPV status. Although there are some discordant results on the prognostic significance of HPV in VSCC, recent evidence indicates a strong association between positive p16 IHC and lower FIGO stage and negative lymph node metastasis, and that the presence of HPV DNA or positive p16 IHC is an independent prognostic factor …”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence indicates that these two different types of VSCC not only have different epidemiological, clinical, pathological and molecular characteristics, but also a different clinical behavior. These differences stress the need of considering HPV‐associated and ‐independent vulvar tumors as two separate entities …”

Section: Introductionmentioning

confidence: 99%

"Histological characteristics of HPV‐associated and ‐independent squamous cell carcinomas of the vulva: A study of 1,594 cases”

Rakislova

Clavero

Alemany

et al. 2017

Intl Journal of Cancer

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There are at least two different etio-pathogenic pathways for the development of vulvar squamous cell carcinoma (VSCC): one associated with infection by human papillomavirus (HPV) and another independent of HPV. We aimed to describe the histological characteristics of HPV-associated and -independent tumors and to determine the best strategy to identify HPV in VSCC. A single paraffin block was available for review from a series of 1,594 VSCCs. In all cases HPV DNA detection was analyzed using the SPF10PCR/DEIA/LiPA25 system and p16 immunohistochemistry (IHC). A tumor was considered as unquestionably HPV-associated if both HPV DNA and p16 IHC were positive. A tumor was considered indisputably HPV-independent if both HPV DNA and p16 IHC were negative. Two groups of tumors were classified as non-conclusive: (1) HPV DNA+/p16- and (2) HPV DNA-/p16+. WHO typing and a thorough histological evaluation were conducted in all cases. Four hundred and forty-one tumors were HPV DNA+ with 367 cases (23.0%) being HPV DNA+/p16+. The latter tumors were more frequently basaloid or warty (49.8%), but 36.5% were of the keratinizing type; 1,153 tumors were HPV DNA-, with 1,060 cases (66.5%) being HPV DNA-/p16-. These HPV DNA-/p16- tumors were mostly keratinizing (81.2%) but were occasionally basaloid or warty (5.2%). The features of HPV DNA-/p16+ cases (n = 93) were similar to those of the HPV-associated VSCC, and HPV DNA+/p16- (n = 74) cases had a more diverse profile, although they were more similar to HPV-independent tumors. Several histological characteristics were more frequently associated with HPV-related VSCC (koilocytotic-like change, necrosis, moderate to marked pleomorphism, invasive front in nests; p < 0.001), however, none of these characteristics allowed differentiation between HPV-associated and -independent VSCC. In conclusion, histological criteria do not allow differentiation between HPV-associated and -independent VSCC. p16 Alone is a clinically easy strategy to determine HPV status in VSCC.

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“…Recurrence rate is higher in pre-malignancies caused by HPV, but less progression to invasive tumours is observed. [24,25]. However, some studies have shown that HPV indicates a less aggressive tumour form with less potential of recurrence [26,27].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Age on the Prognosis of Vulvar Cancer

Hami

Lampe²,

Mallmann

et al. 2018

Oncol Res Treat

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Introduction: Younger women are particularly affected by the increase in the incidence of vulvar cancer. The purpose of this study was to investigate how clinical characteristics differ depending on the patient´s age and what role the age of initial diagnosis plays in the prognosis. Patients andMethods: Included patients were divided into groups aged below or above 50 years. The disease-free survival (DFS) was calculated and a multivariate discriminant analysis was conducted. Results: Of the 300 patients, 79 were ≤50 years and 221 were >50 years. The median age was 64 years (19-96 years). There were no differences between the groups regarding lymph node (LN) status and distant metastasis, but T1 tumours were more frequent in patients ≤50 years (77% vs. 62%, p = 0.02). The DFS only differed between the groups when there were no LN metastases. The nodal status was the predominant prognostic factor for the DFS regardless of age. In node-free patients, the 5-year DFS was 49% for the ≤50 years group and 89% for the >50 years group (p = 0.008), whereas there was no difference if a LN was involved. Conclusion: In node-free patients, the risk for recurrence is lower for patients older than 50 years.

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HPV status and favourable outcome in vulvar squamous cancer

Cited by 60 publications

References 30 publications

Does HPV status influence survival after vulvar cancer?

Does HPV status influence survival after vulvar cancer?

"Histological characteristics of HPV‐associated and ‐independent squamous cell carcinomas of the vulva: A study of 1,594 cases”

The Impact of Age on the Prognosis of Vulvar Cancer

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