p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias

Neffen, Eduardo; Čviko, Aida; Löning, Thomas; Crum, Christopher P.; Riethdorf, Lutz

doi:10.1016/j.humpath.2004.09.004

Cited by 111 publications

(79 citation statements)

References 29 publications

(14 reference statements)

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“…The latter possibility is supported by cervical cancer studies where an increase in HPV detection rate may link to recent advances in HPV detection systems (Li et al, 2011). However, it should be noted that the regional difference in HPV prevalence between North America and Europe could still be observed in the recent studies using the current sensitive HPV detection assays (50-70% vs 15-35%, respectively) (Riethdorf et al, 2004;Sutton et al, 2008;Kowalewska et al, 2010;Alonso et al, 2011;Gargano et al, 2012;de Sanjose et al, 2013).…”

Section: Discussionmentioning

confidence: 97%

HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

Siriaunkgul

Settakorn²,

Sukpan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 97%

HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

Siriaunkgul

Settakorn²,

Sukpan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…p16 immunostaining substantially reduces interobserver variability in the diagnosis of precancerous disease (see next paragraphs) [88][89][90][91]163]. Studies also show that diffuse strong p16 staining is highly associated with a positive test result for HPV-16 (or other high-risk HPVs) [169][170][171].…”

Section: Wg4 Recommendation Nomentioning

confidence: 98%

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology

Darragh

Colgan

Cox

et al. 2012

Archives of Pathology &Amp; Laboratory Medicine

630

372

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The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.

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“…INK4a has been described in VIN [21][22][23] and is thought to arise from interaction of the viral protein E7 with Rb, thus inhibiting Rb function, which results in upregulation of p16 INK4a . Although p16 upregulation is a very sensitive marker for VIN, it does not result in downregulation of the cell cycle because downregulation of its downstream effectors cyclinD1 and cyclinD2 is successfully neutralized by upregulation of cyclinE1, cyclinE2, cyclinA2, cyclinB1 and cyclinB2.…”

Section: Ink4amentioning

confidence: 99%

HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals

Santegoets

Seters

Helmerhorst

et al. 2007

Intl Journal of Cancer

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Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. 1 Differentiated type VIN is mostly found in postmenopausal women and is associated with lichen sclerosus. In contrast, Usual type VIN (undifferentiated) is often diagnosed in premenopausal women and is strongly associated with sexually transmitted Human papilloma virus (HPV) infections. In this report, we will focus on HPVrelated, Usual Type VIN.During the last decade, VIN has been diagnosed with increasing frequency in relatively young women in western countries. This rise in incidence could be the result of a higher awareness and knowledge of VIN, but is more likely to be due to the overall increase in sexually transmitted diseases, and especially the rise in HPV infections. Around 40% of young, sexually active women are infected with high-risk HPV. 2 Fortunately most women are able to clear the infection, and less than 10% of infected women develop a persistent HPV infection which causes dysplasia of the lower genital tract and might cause VIN.3 Such a persistent infection with high-risk HPV (mostly HPV16, 18, 31 or 33) may trigger VIN to further develop into invasive vulvar cancer. What percentage of women with VIN eventually develop cancer is difficult to assess, because most patients with VIN will be treated effectively.van Seters et al. have reviewed data on 3,322 published patients with VIN and found 88 untreated patients, of whom 8 (9%) progressed to vulvar cancer. 4 A critical step in the defence against high-risk HPV is a good immune response. Accordingly, being immunocompromised is a risk factor for the development of VIN and subsequent vulvar cancer. For example, VIN is observed more often ...

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p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias

Cited by 111 publications

References 29 publications

HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

HPV Detection and Genotyping in Vulvar Squamous Cell Carcinoma in Northern Thailand

The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology

HPV related VIN: Highly proliferative and diminished responsiveness to extracellular signals

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