p.8
Recurrence and Progression Risks
What is the risk of progression to vulvar squamous cell carcinoma (VSCC) for vHSIL?
It has a lower and slower risk of progression.
p.4
Diagnosis and Classification of VIN
What are the two morphological variants of HPV-independent disease recognized in vulvar classification?
Vulvar acanthosis with altered differentiation (VAAD) and differentiated exophytic vulvar intraepithelial lesion (DEVIL).
p.7
Recurrence and Progression Risks
What is the 10-year cumulative incidence of VSCC among women with dVIN?
50% (95% CI 21.8 – 78.2%).
p.7
Follow-up and Multidisciplinary Approach
What follow-up is suggested after initial treatment for women with dVIN?
6-monthly follow-up for 2 years, then annual follow-up for 5 years.
p.8
Follow-up and Multidisciplinary Approach
What is required for follow-up in the management of VIN?
Follow-up in a specialist vulval clinic with vulvoscopy and colposcopy, MDT access, and established pathways for colorectal input.
p.8
Multidisciplinary Approach
What is the role of the multidisciplinary team (MDT) in managing rarer squamous intraepithelial precursor lesions?
The natural course and optimal management should be guided by the MDT.
p.1
Diagnosis and Classification of VIN
What are the two distinct disease processes associated with vulval intraepithelial lesions?
High-risk HPV-associated vulval high-grade squamous intraepithelial lesions and HPV-independent differentiated vulval intraepithelial lesions.
p.5
Diagnosis and Classification of VIN
What is the importance of clinicopathological correlation?
It is crucial for identifying subtle signs of HPV-independent disease and commonly occult disease.
p.4
Diagnosis and Classification of VIN
What are the common presentations of HPV-independent dVIN?
Grey or white lesions with a rough surface, white plaques, pink-red plaques, or nodular lesions.
p.5
Medical Management of High-grade Squamous Intraepithelial Lesions
What were the findings of the phase three RCT comparing imiquimod and surgical management?
Noninferiority of imiquimod was demonstrated in a per-protocol analysis, but not in an intention-to-treat analysis.
p.7
Recurrence and Progression Risks
What is the risk of invasive disease even without clinical suspicion in women with dVIN?
There is a risk of invasive disease (cancer) even with a negative biopsy, making follow-up vital.
p.8
Vulval Intraepithelial Neoplasia (VIN) Overview
What are the two types of processes that comprise vulval intraepithelial neoplasia (VIN)?
HR-HPV-associated and HPV-independent processes.
p.5
Diagnosis and Classification of VIN
What are the minimum dimensions for incisional punch or cold knife biopsies?
A minimum of 4-mm width and 5-mm depth relative to adjacent normal skin.
p.3
Histopathological Features of VIN
What are the histopathological features of vulval high-grade squamous intraepithelial lesions (vHSIL)?
Acanthosis, hyperkeratosis, parakeratosis, and signs of reduced cell maturation.
p.7
Patient-Centered Counseling and Ethical Considerations
What are the adverse effects of imiquimod treatment for vHSIL?
Localized pain, swelling, redness, flu-like symptoms (fatigue, headache, muscle or joint pain).
p.3
Diagnosis and Classification of VIN
What are the essential diagnostic features of dVIN identified by expert pathologists?
Basal cell atypia and the absence of p16 immunostaining.
What is the effectiveness of the prophylactic quadrivalent HR-HPV vaccine?
100% effective for the prevention of vHSIL or vaginal HSIL associated with HR-HPV types 16 or 18 among naive women.
p.1
Medical Management of High-grade Squamous Intraepithelial Lesions
What is the first-line medical management for women with biopsy-confirmed vulval high-grade squamous intraepithelial lesions?
Topical treatment in a specialist clinic after adequate counseling on the risk of occult invasive disease.
p.2
Diagnosis and Classification of VIN
What classification system aligns with the ISSVD 2015 update?
Lower Anogenital Squamous Terminology (LAST 2012) and WHO classification (WHO 2014).
p.7
Recurrence and Progression Risks
What is the common risk factor for recurrence in women treated for dVIN?
Positive surgical margins.
p.4
Diagnosis and Classification of VIN
What should prompt consideration of dVIN in patients with lichen sclerosus (LS)?
Nonresponse of LS to an ultra-potent topical steroid.
p.4
Epidemiology and Aetiology of VIN
What is the association of vHSIL with other anogenital diseases?
32% of women with vHSIL and severe dysplasia were associated with other anogenital disease.
p.5
Medical Management of High-grade Squamous Intraepithelial Lesions
What is cidofovir and its properties?
Cidofovir is an antiviral agent with antitumor properties through DNA damage and other mechanisms.
p.8
Medical Management of High-grade Squamous Intraepithelial Lesions
What should be considered after biopsies in the management of VIN?
First-line medical management may be considered by a specialist, with adequate counseling regarding the risk of occult invasive disease.
p.2
Epidemiology and Aetiology of VIN
What was the incidence of dVIN during the later period of 2006-2011?
0.08 per 100,000 person years.
p.5
Diagnosis and Classification of VIN
Why is universal p16 and p53 immunohistochemistry recommended?
To distinguish between vHSIL and dVIN.
p.5
Surgical Management of VIN
What is the historical first-line approach for managing vHSIL?
Surgical management, specifically wide local excision.
p.6
Medical Management of High-grade Squamous Intraepithelial Lesions
What is sinecatechin and what is its primary use?
A green tea extract used for the treatment of genital warts.
p.3
Histopathological Features of VIN
What immunohistochemical markers are associated with vHSIL?
p16 positivity and low expression of p53.
p.6
Surgical Management of VIN
What is the recommended approach for surgical excision of vHSIL?
Should be individualized and patient-led after discussing risks and benefits.
p.4
Histopathological Features of VIN
What histological features characterize VAAD?
Acanthosis with verruciform architecture, parakeratosis, and loss of the granular cell layer.
p.4
Histopathological Features of VIN
What mutations are considered distinct in VAAD/DEVILs?
Absence of TP53 mutation and presence of PIK3CA mutation.
p.6
Medical Management of High-grade Squamous Intraepithelial Lesions
What is the mechanism of action of sinecatechins?
Inhibition of viral oncoproteins E6 and E7 and disruption of viral replication.
p.6
Surgical Management of VIN
What is the role of laser therapy in the management of vHSIL?
Ablation using carbon dioxide laser may be effective, but invasive disease must first be excluded.
p.6
Surgical Management of VIN
What is photodynamic therapy (PDT) and its mechanism?
Involves administration of a photosensitising agent combined with a light source to induce cell death.
p.6
Surgical Management of VIN
What are common adverse effects of photodynamic therapy?
Local inflammation, pain, facial oedema, and urticaria.
p.3
Diagnosis and Classification of VIN
Why is the classification of vHSIL into warty, basaloid, or mixed types considered not clinically useful?
Because it does not provide significant clinical differentiation.
p.1
Epidemiology and Aetiology of VIN
What are the two pathways from healthy epithelium to vulval squamous cell carcinoma?
High-risk HPV-associated and HPV-independent processes.
p.1
Diagnosis and Classification of VIN
What classification did the World Health Organization (WHO) introduce in 2020 for vulval intraepithelial neoplasia?
Classification according to HPV status.
p.7
Follow-up and Multidisciplinary Approach
What should women with vHSIL or dVIN be referred to?
A specialist vulval service within a vulval multidisciplinary team (MDT) network.
p.6
Surgical Management of VIN
What is skinning vulvectomy and when is it considered?
A procedure where vulval skin is removed, considered for confluent multifocal lesions in immunocompromised patients.
p.8
Surgical Management of VIN
What is recommended for cases of dVIN due to its high risk of progression?
Surgical excision is recommended.
p.2
Epidemiology and Aetiology of VIN
What are the main risk factors for HPV-independent precursor lesions?
Age and lichen sclerosus (LS).
p.4
Diagnosis and Classification of VIN
What are common clinical manifestations of vHSIL?
Raised papular lesions with well-defined borders and a rough, keratotic surface.
p.5
Medical Management of High-grade Squamous Intraepithelial Lesions
What alternative management has been proven safe and effective for vHSIL?
Medical management, provided there is no suspicion of invasive disease.
p.1
Diagnosis and Classification of VIN
What is the significance of recognizing and classifying the spectrum of vulval intraepithelial lesions?
It has implications for management and the risk of malignant transformation.
p.3
Histopathological Features of VIN
How is differentiated vulvar intraepithelial neoplasia (dVIN) distinct from vHSIL?
dVIN has pathognomonic differentiation compared to the undifferentiated appearance of vHSIL.
p.3
Histopathological Features of VIN
What does the presence of abnormal patterns of p53 immunostaining suggest in dVIN?
It indicates several abnormal patterns of p53 expression.
p.2
Diagnosis and Classification of VIN
What are the recognized classifications of vulval lesions according to ISSVD 2015?
Low-grade squamous intraepithelial lesion (LSIL), vHSIL, and dVIN.
p.2
Epidemiology and Aetiology of VIN
What is the incidence rate of vHSIL according to a population-based study in the Netherlands?
2.99 per 100,000 person years between 1991 and 2011.
p.7
Diagnosis and Classification of VIN
What is recommended for suspected differentiated vulvar intraepithelial neoplasia (dVIN)?
Surgical excision is recommended due to the risk of occult disease and higher progression rates to vulvar squamous cell carcinoma (VSCC).
p.6
Medical Management of High-grade Squamous Intraepithelial Lesions
What is the primary use of 5-fluorouracil (5-FU)?
For the medical management of vHSIL.
p.5
Medical Management of High-grade Squamous Intraepithelial Lesions
What is imiquimod and its mechanism of action?
Imiquimod is an immunomodulator that induces an inflammatory pathway and cellular immune response.
p.3
Histopathological Features of VIN
What does block positive p16 staining indicate?
It is indicative of HPV status in vHSIL.
p.3
Epidemiology and Aetiology of VIN
What does the identification of HR-HPV-positive lesions with differentiated-type morphology suggest?
It suggests a nuanced spectrum of disease and underscores the importance of typing disease according to p53 and p16.
p.2
Epidemiology and Aetiology of VIN
What is the relationship between lichen sclerosus and dVIN?
There is no clear evidence of a causal relationship.
p.6
Medical Management of High-grade Squamous Intraepithelial Lesions
What was the complete clinical resolution rate reported in a study involving 5-FU?
74% at a median follow-up of 18 months.
p.5
Medical Management of High-grade Squamous Intraepithelial Lesions
What were the results of the phase 2 RCT comparing imiquimod and cidofovir?
Both were safe and effective, with cidofovir showing fewer moderate or severe adverse effects.
p.3
Histopathological Features of VIN
What are the typical features of dVIN?
Parakeratosis, elongated and anastomosing rete ridges, atypia in basal cells, abnormal keratinocytes, and prominent intracellular bridges.
p.1
Patient-Centered Counseling and Ethical Considerations
What ethical consideration must be taken into account when treating vulval intraepithelial lesions?
Treatment must be tailored towards the patient’s appreciation of risk and benefit.
