Vulval Intraepithelial Neoplasia (VIN)

Definition

Classification

ISSVD 1986 / WHO (Classic Grading - Novak)

Current ISSVD 2015 / WHO 2014 Classification (Updated)

• HPV-associated (mainly HPV-16)
• Younger women (reproductive age)
• Subtypes: warty, basaloid, mixed
• p16 positive on immunostaining
• 10-15% risk of progression to invasive SCC if untreated

• HPV-independent
• Older women (postmenopausal)
• Associated with lichen sclerosis and lichen simplex chronicus
• TP53 mutations common
• Higher malignant potential - faster progression to invasive SCC (~30%)
• p16 negative; p53 aberrant expression

Note: VIN 1 is no longer considered a precancerous lesion per ACOG guidelines. It is most often an HPV effect and does not require treatment.

Epidemiology

• Incidence increasing, especially in young women
• HPV-associated SCC: 30% of all vulvar cancers, younger women (avg 30 years)
• HPV-independent SCC: 70% of cases, older women (avg 75 years)
• 10-30% of VIN patients have concurrent cervical or vaginal HPV lesions (multicentric disease)

Etiology and Risk Factors

• High-risk HPV infection (especially HPV-16)
• Early sexual debut, multiple sexual partners
• Immunosuppression (HIV, transplant)
• Smoking
• History of CIN or VaIN

• Chronic lichen sclerosis
• Lichen simplex chronicus
• Older age
• TP53 somatic mutations (and other: PIK3CA, NOTCH1, HRAS)

Clinical Features

• Symptoms: Pruritus (most common), burning, pain, dysuria; may be asymptomatic
• Appearance: Variable - white hyperkeratotic plaques, erythematous areas, pigmented/raised lesions, warty or papular lesions
• Location: Labia majora most common; may involve labia minora, perineum, perianal skin, clitoris
• Multifocal VIN 3 - multiple small hyperpigmented lesions on labia majora
• Bowenoid papulosis - multiple small pigmented papules (<5 mm), young women, may regress postpartum (term no longer recommended by ISSVD)

FIGURE 16-18: Carcinoma in situ of the vulva (VIN 3) - Berek & Novak's Gynecology

Histopathology

• Epidermal thickening, nuclear atypia, increased mitoses
• Lack of cellular maturation
• Koilocytes (HPV cytopathic effect) - perinuclear halos, binucleation, multinucleation
• Dyskeratotic cells in superficial layers
• VIN 3: immature cells with scanty cytoplasm and severe chromatin changes occupying most of epithelium

• Keratinizing, well-differentiated cells
• Basal layer atypia, elongated rete ridges
• Less obvious nuclear atypia - easily missed
• TP53 mutations

Diagnosis

1. Clinical inspection - bright light, magnifying glass; careful vulvar exam at annual check
2. Colposcopy with acetic acid - acetowhite lesions
3. Biopsy - MANDATORY for all suspicious lesions; directed biopsy of darkest/raised areas
4. Immunohistochemistry: p16 (positive in uVIN), p53 (aberrant in dVIN)
5. Concurrent cervical and vaginal examination (multicentric disease)

Progression Risk

Management

VIN 1

• No treatment required (not a precancerous lesion per ACOG)
• Observation; address underlying HPV

VIN 2

• p16 positive: Treat as VIN 3
• p16 negative: Can be observed

VIN 3 / High-grade VIN - Treatment Options

1. Wide local excision - preferred for unifocal disease; provides histology; repeat excision often needed but usually avoids vulvectomy
2. Superficial (skinning) vulvectomy - for extensive/recurrent/multifocal VIN 3; goal is to preserve normal anatomy, clitoris, and anterior vulva
3. Split-thickness skin grafting - when primary closure not possible (harvest from thigh or buttock)

Surveillance / Follow-up

• Regular vulvar inspection every 6-12 months (lifelong)
• Recurrence is common after all modalities
• Annual cervical smears (multicentric HPV disease)
• Screen sexual partners

Prevention

• HPV vaccination (9-valent vaccine - Gardasil 9) - prevents HPV-16/18 related uVIN
• Smoking cessation
• Safe sexual practices

Key Points for DNB Exam

Latest Updates (2024-2026)

• The ISSVD 2015 binary classification (uVIN vs dVIN) is now standard - the three-tier VIN 1/2/3 system is largely replaced in current practice, though VIN 3 language persists in older literature
• dVIN is now recognized as a high-risk lesion - its lack of florid atypia makes it frequently under-diagnosed; p53 IHC is recommended when dVIN is suspected
• New molecular subtypes of HPV-independent VIN lacking TP53 mutations have been described (PIK3CA, NOTCH1, HRAS mutations) - ongoing reclassification expected (Robbins 10th ed.)
• Imiquimod is increasingly used as first-line for multifocal uVIN, with remission rates of 35-81% in trials
• Vaccination of all eligible individuals emphasized as a preventive strategy (Swaminathan et al., Clin Obstet Gynecol 2026, PMID 41928602)
• Formal screening guidelines for vulvar disease remain limited - major gap identified in current literature

Emergency LSCS in a 22-year-old with PIH and Fetal Distress - Perioperative Plan

PART A: PREOPERATIVE ASSESSMENT [3 marks]

Rapid Structured Assessment (Emergency Setting)

• Duration and severity of PIH: BP readings, proteinuria (preeclampsia with severe features vs mild)
• Symptoms of severe preeclampsia: headache, visual disturbance, epigastric pain, oliguria
• Fetal distress pattern: type of CTG abnormality (late decelerations, loss of variability, bradycardia)
• Last oral intake (aspiration risk - full stomach assumed in emergency)
• Drug history: antihypertensives (labetalol, nifedipine), MgSO4 infusion (affects muscle relaxants), steroids

• Mallampati grading, mouth opening, neck mobility
• Preeclampsia causes edema of tongue, epiglottis and pharynx - significantly increases risk of difficult/failed intubation
• Higher-grade airways mandate preparation for awake fiberoptic or video laryngoscopy (Barash 9e)

• Repetitive late decelerations
• Loss of fetal beat-to-beat variability with late/deep decelerations
• Sustained FHR < 80 beats/min
• Fetal scalp pH < 7.20
• Meconium-stained liquor

• Control BP: IV labetalol 5-10 mg increments or IV hydralazine or IV nicardipine (target BP <160/110 mmHg)
• MgSO4: loading dose 4-6 g IV over 20-30 minutes if not already given; maintenance 1-2 g/hr (seizure prophylaxis)
• Antacid prophylaxis: sodium citrate 30 mL orally + IV ranitidine/metoclopramide (aspiration prophylaxis - full stomach)
• Left lateral tilt / uterine displacement (aortocaval decompression)
• Establish large-bore IV access x2; arterial line if severe hypertension
• Consent (usually verbal/implied in emergency)
• Paediatric/neonatal team alert (neonatal resuscitation standby)

PART B: ANAESTHESIA [4 marks]

Choice of Anaesthesia

• Avoids the major risk of failed/difficult intubation (leading cause of maternal death in obstetric anaesthesia)
• Avoids aspiration risk
• Reduces circulating catecholamines, attenuates hypertensive response to pain
• Improves uteroplacental perfusion by up to 75% (Barash 9e)
• Allows mother to be awake at delivery

• Contraindication to neuraxial (thrombocytopenia <70,000, coagulopathy, patient refusal)
• True emergency ("crash") with inadequate time for regional
• Failed regional block

Option 1: Spinal Anaesthesia (preferred for emergency LSCS)

• Position: sitting or left lateral
• Level: L3-L4 or L2-L3 interspace
• Drug: Hyperbaric bupivacaine 0.5% - 10 to 12.5 mg (2-2.5 mL) + fentanyl 15-25 mcg + intrathecal morphine 100 mcg (for postoperative analgesia)
• Target sensory block: T4-T6 (nipple line)
• Note on preeclampsia: Contrary to older concerns, spinal anaesthesia does NOT cause more severe hypotension in preeclampsia compared to normotensive women; current evidence supports its safety (Barash 9e; Creasy & Resnik)

• Phenylephrine is preferred vasopressor (over ephedrine) - less fetal acidosis
• IV fluid co-load with crystalloid at time of spinal insertion
• Avoid excessive preload (risk of pulmonary oedema in preeclampsia)
• Left uterine displacement maintained throughout
• Monitor BP every 2-3 minutes after spinal

Option 2: Epidural Anaesthesia (if epidural already in situ from labour)

• Top up with 3% chloroprocaine (fastest onset - 5-10 min) or 2% lignocaine with adrenaline and bicarbonate (alkalinised for speed)
• Combined spinal-epidural (CSE) also an option

Option 3: General Anaesthesia (when regional not possible)

• Induction: Thiopentone 4-5 mg/kg IV or Propofol 2 mg/kg (use ketamine 1 mg/kg if hypotensive)
• Note: Ketamine and ergot alkaloids should be AVOIDED in uncontrolled hypertension (worsens BP)
• Muscle relaxant: Suxamethonium 1.5 mg/kg IV (Sellick's maneuver/cricoid pressure simultaneously)
• If MgSO4 on board: reduce dose of non-depolarizing relaxants (MgSO4 potentiates neuromuscular blockade - monitor with nerve stimulator)
• Video laryngoscope immediately available; difficult airway trolley at bedside
• Intubate with cuffed ETT; confirm with capnography

• Isoflurane/sevoflurane + 50% N2O in O2
• Avoid high-dose volatile agents before delivery (uterine relaxation, neonatal depression)
• After delivery: convert to opioid-based analgesia (fentanyl), reduce volatile agent

• IV labetalol 5-10 mg before laryngoscopy
• IV nicardipine or clevidipine for intraoperative hypertension
• Intra-arterial BP monitoring (arterial line) recommended in severe hypertension

Intraoperative monitoring (all cases)

• Continuous pulse oximetry, capnography (if GA), ECG
• Non-invasive BP every 2-3 minutes (invasive arterial line in severe disease)
• Urine output monitoring (catheter - target >25 mL/hr)
• Temperature, peripheral nerve stimulator (if MgSO4 + non-depolarising relaxants)
• Continuous FHR monitoring in OT until delivery

PART C: POSTOPERATIVE ANALGESIA [3 marks]

Multimodal Analgesia - Gold Standard (Barash 9e)

• Provides prolonged (12-24 hr) visceral and somatic pain relief
• Side effects: nausea/vomiting, pruritus, urinary retention
• Delayed respiratory depression - rare but potentially devastating; mandatory monitoring (respiratory rate, sedation score) for 24 hours after neuraxial morphine

• Paracetamol (acetaminophen) 1g IV/oral every 6 hours (safe, reduces opioid requirement)
• NSAIDs - Ibuprofen 400-600 mg oral 8 hourly or ketorolac 15-30 mg IV (use with caution in preeclampsia - monitor BP and renal function; avoid if significant proteinuria/renal impairment or oliguria)

• Oral oxycodone or IV morphine PCA as required
• Avoid codeine and tramadol (unsafe in breastfeeding mothers - codeine: risk of neonatal respiratory depression via CYP2D6 ultrametabolisers; tramadol similarly)

• Transversus abdominis plane (TAP) block - bilateral; covers somatic anterior abdominal wall pain (T8-L1); gives 8-12 hours analgesia
• Quadratus lumborum (QL) block - provides broader coverage including visceral pain
• Wound infiltration with long-acting local anaesthetic (levobupivacaine/ropivacaine) if TAP not feasible

• Early mobilisation
• Ice packs to wound
• Supportive positioning

Monitoring in the Postoperative Period

• BP monitoring every 15 minutes for 1 hour, then hourly (PIH may worsen 24-48 hours postpartum)
• Continue MgSO4 for 24 hours postdelivery (eclampsia risk highest in first 24 hours postpartum)
• Urine output, deep tendon reflexes (MgSO4 toxicity: hyporeflexia, respiratory depression - antidote: calcium gluconate 1g IV over 10 min)
• Respiratory monitoring hourly if neuraxial morphine given
• Watch for HELLP syndrome (platelet count, LFTs at 24-48 hours)
• Breastfeeding: most standard analgesics safe; avoid codeine/tramadol

Summary Table