Vulvar and vaginal cancer

• Vulvar and vaginal cancers are uncommon (vulvar cancer about 4% of gynaecological cancers and is the 19th most common cause of cancer in women in Europe), but their incidence is rising in women under 60, driven by human papillomavirus (HPV) infection ^[1][2][3].
• Vulvar squamous cell carcinoma (SCC) arises through two main routes: an HPV-associated route via high-grade squamous intraepithelial lesion (HSIL), and an HPV-independent route arising on a background of lichen sclerosus and differentiated vulvar intraepithelial neoplasia (dVIN) ^[3].
• Lichen sclerosus carries a lifetime risk of about 2 to 5% of vulvar SCC, and up to 65% of vulvar carcinomas arise against a background of lichen sclerosus ^[6].
• Vaginal cancer is clinically staged like cervical cancer; radiotherapy is its main treatment, with chemoradiotherapy improving survival in retrospective series ^[4].
• A vulval lump, ulcer, or persistent itch should be biopsied rather than treated by excision first, because excision first disrupts staging and treatment planning ^[1].
• Clear cell adenocarcinoma of the vagina and cervix is caused by in-utero exposure to diethylstilbestrol (DES): DES daughters have about 40 times the risk of unexposed women, yet the tumour is still rare (about 1 in 1,000 DES daughters) ^[5].

By the end of this page you should be able to:

1. Define the principal types of vulvar and vaginal cancer and describe the two vulvar SCC pathways.
2. Explain why chronic unopposed estrogen and HPV or lichen sclerosus lead to these cancers.
3. Recognise the typical symptoms and signs of vulvar cancer and vaginal cancer.
4. Stage vulvar cancer with the FIGO 2021 system and vaginal cancer with the FIGO staging system.
5. Explain the current treatment of vulvar squamous cell carcinoma by ESGO 2023 and the BGCS 2023, including margins, sentinel lymph nodes, radiotherapy doses, and chemotherapy.
6. Describe the management of vaginal cancer, including surgery, radiotherapy, and chemoradiotherapy with doses.
7. Explain the DES story, clear cell adenocarcinoma, and what follow-up is recommended.
8. Distinguish vulvar/vaginal cancer from benign vulval skin disease, VIN, melanoma, and other mimics.

• Vulvar squamous cell carcinoma (SCC) is by far the commonest vulvar cancer (more than 80%), followed by melanoma (about 5%), then basal cell carcinoma, verrucous carcinoma, adenocarcinoma related to extramammary Paget disease, Bartholin gland carcinoma, and sarcoma ^[3].
• Two SCC pathways. Keratinizing SCC occurs in older women, is HPV-negative, and arises on a background of lichen sclerosus and/or dVIN. Warty/basaloid SCC occurs in younger women, is driven by persistent infection with oncogenic HPV (HPV 16, 18, 31, 33), and arises from HSIL ^[3].
• Vulvar intraepithelial neoplasia (VIN). Current terminology (LAST) divides lower anogenital squamous lesions into low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL; covering the former usual-type/warty/basaloid and mixed VIN), and differentiated VIN (dVIN) ^[3]. dVIN represents less than 5% of preneoplastic vulvar lesions, yet has a higher progression rate, shorter time to invasive cancer, and higher recurrence than HSIL, and is rarely HPV-associated (less than 2%) ^[3].
• Lichen sclerosus is a chronic inflammatory skin disease with autoimmune features, anogenital distribution, and scarring; women affected with lichen sclerosus have a lifetime risk of developing squamous cell carcinoma of about 2 to 5%, and up to 65% of vulvar carcinomas arise on a background of lichen sclerosus ^[6]. ^[7]
• HPV-associated SCC is classified by the WHO as HPV-associated SCC on the basis of "block-type" p16 immunohistochemistry (mandatory), with wild-type p53 staining; HPV-independent SCC (and dVIN) shows "mutation-type" p53 ^[1].
• Vaginal cancers are most commonly squamous (HPV-associated, especially HPV 16); adenocarcinomas are rarer, and clear cell adenocarcinoma dominates in the DES-exposed population ^[4].
• Vulvar melanoma is the second most common vulvar cancer but very rare (0.1 per 100 000); mucosal melanomas have a 5-year survival of only about 15%. FIGO staging does not apply to melanoma; the Clark/Breslow AJCC melanoma system is used ^[3]. ^[6]

• Vulvar SCC accounts for about 4% of gynaecological cancers globally; around 65% of cases arise in higher-income regions ^[2]. The FIGO Committee noted 16,506 new vulvar cancers in Europe in 2020, predominantly in elderly women, though incidence is rising in women under 60 ^[1][3].
• Kang et al. found a significant overall 14% increase in vulvar cancer incidence across 13 high-income countries, 38% in women under 60, attributed to rising HPV infection rates among women born after the 1960s ^[3].
• Subtypes by age. Basaloid and warty (HPV-associated) SCC represent about one-third of cases and occur in younger women. Keratinizing (HPV-independent) SCC occurs in older women and arises from lichen sclerosus ^[2].
• Vaginal cancer is rare: about 1 to 2% of all gynaecological malignancies; the median age at diagnosis for all vaginal cancers is about 67 to 68 years, with adenocarcinoma diagnosed more often in younger women, often under 30 ^[4].
• HPV attribution. HPV prevalence is ~69% in warty/basaloid vulvar SCC (commoner in younger women) versus ~13% in keratinizing SCC of older women ^[3].
• DES exposure. Prenatal DES exposure affected 5 to 10 million Americans (1940 to 1971), with the drug used in Europe until 1978; DES daughters have the clear cell peak at age 17 to 21 ^[5][4].

• Age, HPV infection, smoking, HIV infection, vulvar intraepithelial neoplasia, and lichen sclerosus are the principal epidemiologic risk factors ^[1].
• HPV-associated: persistent infection with high-risk HPV, especially HPV 16, plus smoking and HIV. HSIL (usual-type VIN) is the precursor ^[1][3].
• HPV-independent: chronic lichen sclerosus or lichen planus, dVIN, smoking, and (rarely) northern European descent; these occur more in older, postmenopausal women ^[1][3].
• Lichen sclerosus and lichen planus. In dermatological and gynaecological reviews, the lifetime risk of vulvar SCC in lichen sclerosus is about 2 to 5%, with higher risk in women who do not adhere to long-term maintenance topical steroid treatment ^[6]. Lichen planus is also a recognised precursor of HPV-independent vulval SCC, reported with similar though slightly different risks ^[7].
• dVIN. dVIN represents under 5% of preneoplastic vulvar lesions but progresses more rapidly and recurs more often than HSIL, so excision is the treatment of choice ^[3].
• Paget disease of the vulva (adenocarcinoma in situ) and melanoma in situ are rare but may progress and are followed in special clinics ^[1] (see below).

The review by Hong and Ding (2025) lists DES exposure (highest risk during the first 16 weeks of gestation), age, persistent high-risk HPV (strong for SCC, less so for adenocarcinoma), immunosuppression (HIV), and smoking (which more than doubles risk in HPV-positive women) as risk factors for vaginal cancer ^[4]. DES remains the most specific and significant risk factor for the clear cell subtype ^[4][5].

• HPV vaccination reduces non-cervical premalignant lesions with vaccine efficacies over 90%, and Norwegian long-term trends predict fewer HPV-associated vulvar cancers in vaccinated communities ^[3].
• Secondary prevention (screening). There is no evidence for specific screening for vulvar cancer. Self-examination in women with lichen sclerosus is encouraged, and suspicious lesions should be biopsied. Women with cervical, vaginal, or anal SILs should have the vulva inspected during follow-up ^[3].
• Tertiary prevention. Timely treatment of predisposing lesions (lichen sclerosus with ultrapotent topical steroids, HSIL by excision or imiquimod) reduces incidence ^[3].

1. Persistent infection of the squamous epithelium of the vulva with high-risk HPV (16, 18, 31, 33) causes low-grade then high-grade squamous intraepithelial change (LSIL then HSIL/uVIN), driven by the viral oncogenes E6 and E7, which inactivate the tumour suppressors p53 and pRb ^[3].
2. HSIL/uVIN remains confined to the epithelium; with further molecular change it invades as warty/basaloid SCC, more often in younger women, often with multifocal disease and other lower-genital-tract SIL ^[3].

1. Chronic lichen sclerosus imposes a T-helper-1-predominant, Th1-driven autoimmune, inflammatory milieu with oxidative DNA damage and impaired regulatory T-cell function; the inflammation drives fibroblast activation and collagen hyalinisation ^[6].
2. In this setting dVIN arises (p53 mutation-type, TP53 mutated, p16 negative); dVIN is sharply more progressive than HSIL ^[1][3].
3. Progression of the keratinizing SCC then occurs on a background of "field cancerisation": large areas of genetically altered, lichen-sclerosus- affected epithelium, explaining the tendency to late, remote-site "recurrences" that may actually be new primaries ^[3][1].

Vaginal SCC behaves like cervical SCC (HPV-driven, chiefly HPV 16) and is clinically staged like cervical cancer; clear cell adenocarcinoma instead arises from the adenosis that develops after in-utero DES exposure, with a peak in young women ^[4].

DES is a synthetic estrogen that was prescribed to pregnant women between 1940 and 1971; the FDA advised in 1971 that it not be used in pregnancy ^[5]. Prenatal exposure during the first 16 weeks of gestation appears to carry the highest risk ^[4], and DES daughters have about 40 times the risk of clear cell adenocarcinoma of the lower genital tract, although the absolute risk is only about 1 in 1,000 ^[5]. Clear cell adenocarcinoma of the vagina arises in these daughters, usually in the teens or twenties but sometimes older ^[5][4]. Tumour development in adults without in-utero DES exposure is rare (sporadic clear cell), reinforces which supports a field effect of DES ^[4].

• Macroscopy. HPV-independent SCC is often a single ulcer or mass on the labia, close to the midline, in older women. HPV-associated SCC is more often multifocal and coexists with other lower-genital SILs ^[1].
• Squamous variants. Keratinizing (HPV-negative), basaloid, warty (HPV-associated), and verrucous are the main variants described; keratinizing dominates ^[2].
• Lichen sclerosus shows orthokeratosis, loss of rete ridges, epidermal atrophy, basal degeneration, and homogenised dermal fibrosis; biopsy is recommended when the clinical picture is atypical ^[6].
• VIN. HSIL (usual type) shows atypia and immature keratinocytes confined to epithelium; dVIN shows atypia in the basal layer with parakeratosis and premature terminal differentiation, and is often adjacent to cancer ^[3].
• Paget disease of the vulva is an in situ adenocarcinoma of the skin, rare, high risk of invasion, needs specialist follow-up ^[1].
• Melanoma histology requires IHC (S100, HMB45, Melan A) and records Breslow thickness, Clark level, ulceration, and mitoses; AJCC (8th/9th) staging rather than FIGO is used ^[3].

Vulvar cancer.

• Symptoms are absent in some patients; the commonest presentations are vulvar pruritus or pain, or a lump/ulcer noted by the woman ^[3].
• Other features: abnormal bleeding or discharge, a history of vulvar symptoms from lichen sclerosus or HSIL, or a groin lump from nodal spread in advanced disease ^[3].
• High-risk histories: increasing age; long-standing lichen sclerosus; CIN/HSIL; HIV; smoking; early first sexual activity with multiple partners (for HPV-associated disease) ^[1][3].

Vaginal cancer.

• Abnormal vaginal bleeding (postmenopausal, postcoital, or intermenstrual) is the commonest symptom, in 50 to 75% of cases, followed by vaginal discharge (often malodorous, tumour necrosis), a palpable mass (upper third, posterior wall), pain/dyspareunia, and (less often) itching, urinary or rectal symptoms ^[4].

• Every woman with vulval symptoms should have a low-threshold examination of the whole vulva, vagina, cervix, and anus, because of the multifocal nature of lower anogenital SILs ^[1].
• Vulvar SCC looks like an ulcer, plaque, warty lesion, or exophytic mass on labia, clitoris, perineum, or fourchette; the distribution and midline proximity matter for both nodal drainage and margin planning ^[1].
• Palpate inguinofemoral nodes; document size, mobility, fixation, and skin changes ^[1].
• For vaginal cancer: inspect the vaginal walls fully (posterior-wall lesions can be hidden by the speculum) with vaginal examination under anaesthesia if needed; colposcopy and cystoscopy/proctoscopy assess local extent ^[4].
• Vulvar melanoma presents as a pigmented (or amelanotic) lesion, most often on clitoris or labia minora; high index of suspicion for any new, changing, or non-healing vulval spot ^[3].

VIN and early cancer are particularly easy to miss: the visual changes can be subtle, and women often self-treat for years before biops. Hence the low threshold for biopsy in any persistent or atypical vulval lesion. ^[7]

FIGO 2021 is data-derived (NCDB 2010 to 2017), has two substages in Stage I, three in Stage III, two in Stage IV, and uses a new depth-of-invasion measurement (from the basement membrane of the deepest adjacent dysplastic, tumour-free rete ridge to the deepest point of invasion) ^[2]. It applies to all morphological types of vulvar cancer except melanoma ^[2][3].

Note the key 2021 change: depth of invasion is now measured from the deepest adjacent dysplastic rete ridge (an alternative method that can downstage some former IB cases to IA). The FIGO Committee also uses node micrometastasis/macrometastasis definitions as in cervical cancer; isolated tumour cells (ITC) do not count as lymph-node metastasis ^[2].

Vaginal cancer is staged clinically (examination, biopsy, imaging), in the FIGO system (last revised by AJCC eighth-edition in parallel), with substages below ^[4].

Tumours involving cervix or vulva are reclassified as cervical or vulvar primaries regardless of epicentre ^[4].

• Historically, surgeons aimed for a pathological tumour-free margin of at least 8 mm; recent large studies (including ESGO and the 2025 update) have not consistently confirmed a relation between margin distance and local recurrence, but a surgical margin of less than 5 mm remains associated with recurrence ^[1][3].
• The ESGO 2023 group advises aiming for tumour-free margins (a pathological minimal margin above 2 to 3 mm seems sufficient), while the 2025 update advises a 1 to 2 cm surgical margin to achieve at least 3 mm pathologically, given the understanding that many "recurrences" are new primaries arising in a field of cancerisation ^[1][3].
• Extending excision superficially to include adjacent dVIN is highly recommended ^[1].

Guidelines used: ESGO 2023 vulvar cancer guidelines (Oonk et al., Int J Gynecol Cancer 2023), the FIGO 2021 vulvar staging (Olawaiye et al., Int J Gynecol Obstet 2021), the FIGO cancer report 2025 (Olawaiye et al., Int J Gynecol Obstet 2025), national/BGCS 2023 vulval cancer updates, and RCOG Green-top No. 58 for vulval skin disorders ^[1][2][3][7].

Treatment aims to cure with the least morbidity and is planned in an MDT experienced in vulvar disease ^[1].

• Radical local excision of the tumour is preferred over radical vulvectomy (better morbidity, equal local control) ^[3]; reconstructive surgery is considered for large defects ^[3].
• Margins. Surgeons historically aimed for 8 mm tumour-free, but newer evidence weakens the margin-recurrence link. The ESGO 2023 guidance favours secure tumour-free margins (pathological 2 to 3 mm acceptable); the 2025 update advises 1 to 2 cm surgical margins, accepting at least 3 mm pathologically ^[1][3].
• Stage IA (up to 2 cm, invasion 1 mm or less): radical wide local excision alone; no groin dissection is needed ^[3].
• Microinvasive disease. Where the first biopsy shows a lesion no more than 2 cm and invasion 1 mm or less, complete radical local excision is performed to confirm the maximum depth, and if no part exceeds 1 mm, excision alone is definitive ^[3].
• Lymph nodes. Any primary unifocal tumour greater than 1 mm in invasion with no suspicious nodes: sentinel lymph node biopsy. Tumours 4 cm or more, or multifocal invasive disease: inguinofemoral lymphadenectomy, bilateral if non-lateralised (medial border less than 1 cm from midline) ^[1][3].
• SLN procedure (GROINSS-V). Indications: unifocal tumour confined to the vulva, less than 4 cm in diameter, stromal invasion greater than 1 mm, clinically and radiologically negative groins. Identify with radio-labelled technetium plus blue dye (or indocyanine green as an emerging alternative); combined detection is most accurate. If no SLN is found, perform lingual/groin lymphadenectomy; if nodes are midline, bilateral detection is mandatory ^[1][3].
• Micrometastasis (2 mm or less) or ITC in SLN. Postoperative radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (GROINSS-V II: groin recurrence rate 1.6% with RT versus 11.8% without in micrometastatic disease; 0% with RT for ITC) ^[1][3]. In GROINSS-V II, radiotherapy started within 6 weeks of surgery at 50 Gy in 25 to 28 fractions of 1.8 to 2 Gy, 5 fractions per week ^[1]. ^[6]
• Macrometastasis (more than 2 mm) in the SLN. Inguinofemoral lymphadenectomy of the affected side, with postoperative radiotherapy when further positive nodes or extracapsular spread are found (GROINSS-V II: 22% groin recurrence with RT alone in macrometastasis, better with surgery first) ^[1][3].
• When inguinofemoral lymphadenectomy has been done, radiotherapy is recommended for more than one positive node or extracapsular spread, with concurrent radiosensitizing chemotherapy considered ^[1].
• Adjuvant vulvar radiotherapy dose. After surgery, postoperative RT to the vulva for positive margins (no re-excision possible) or risk factors (close margins, LVSI, perineural invasion, large tumour, invasion depth greater than 5 mm) ^[1]. Elective dose to inguinofemoral/iliac regions 45 to 50.4 Gy in 1.8 to 2 Gy fractions; boost to 54 to 56 Gy EQD2 for macroscopic nodal disease removed without residual (boost up to 64 to 66 Gy, or 60 to 66 Gy for positive vulvar margins using EBRT or image-guided adaptive brachytherapy) ^[1].
• Optimal treatment time. Complete adjuvant radiotherapy within 104 days of surgery (interval surgery to start RT maximum 8 to 10 weeks; total OTT no more than 8 weeks) because each additional day raises mortality risk ^[1].

• Vaginal squamous/vaginal adenocarcinoma. For stage I disease, especially upper vaginal tumours smaller than 2 cm, standard treatment is surgical excision/radical hysterectomy with partial or total vaginectomy and pelvic or inguinal lymphadenectomy depending on tumour height (pelvic nodes for upper two-thirds, inguinal for lower third of vagina) ^[4].
• Stage II to IVA vaginal cancer. Radiotherapy (EBRT, brachytherapy, or both) is the standard: combination of EBRT and brachytherapy, with involved nodal treatment as for cervical cancer ^[4].
• Brachytherapy dose for very early vaginal lesions (less than 5 mm depth, no EBRT needed): low dose-rate 60 to 70 Gy EQD2 to the vaginal surface; high dose-rate generally 50 to 60 Gy EQD2, for example 5 Gy x 8 fractions or 8 Gy x 5 fractions to the vaginal surface twice weekly ^[4].
• Chemoradiation. Retrospective data in vaginal cancer support concurrent chemotherapy (cisplatin or 5-FU based) combined with radiation. The EBRT component in locally advanced vaginal disease follows cervical-cancer standards, with HDR 64 to 70 Gy EQD2 to primary disease sometimes emerging; many protocols use cisplatin 75 mg/m2 day 1 plus 5-FU 1000 mg/m2/day days 2 to 5, with carboplatin as an alternative if cisplatin is not tolerated ^[4]. An 8,222-patient retrospective cohort showed chemoradiation improved median overall survival versus radiation alone ^[4]. Because direct randomised trials in vaginal cancer are lacking, management extrapolates from cervical cancer plus ESGO 2023 vaginal (ESTRO/ESGO/SIOPe) guidance ^[1].
• Fertility preservation. For young patients with early, small vaginal adenocarcinoma who want fertility, ovarian preservation or transposition and radical trachelectomy with upper vaginectomy may be considered in specialist hands ^[4].

• Primary chemoradiotherapy is the treatment of choice for unresectable vulvar disease or tumours needing exenteration: total vulvar dose 64 to 70 Gy EQD2 in 1.8 to 2 Gy per fraction, elective nodes 46 to 50.4 Gy, and macroscopic disease can be boosted to 60 to 66 Gy EQD2; concurrent cisplatin (40 mg/m2 weekly, up to 70 mg/m2 per cycle) with up to 57.6 Gy in 32 fractions (GOG 205) gave 50% pathological complete response ^[1]. Treatment breaks should be avoided (more than 50 days prolongs recurrence risk) ^[1].
• Advanced disease often needs combined surgery and (chemo)radiation and neoadjuvant cisplatin/paclitaxel is an option for bulky nodes ^[3].
• Metastatic or recurrent disease. Platinum-based combination chemotherapy (cisplatin or carboplatin plus paclitaxel) is considered first line; VEGF/immunotherapy agents (bevacizumab, pembrolizumab, nivolumab) are options by extrapolation from cervical data but carry no specific European approval for vulvar cancer ^[1]. Pembrolizumab produced 10.9% response in recurrent/metastatic vulvar cancer in KEYNOTE-158 ^[3]; nivolumab gave a 20% response rate in HPV-associated vulvovaginal cancer in CHECKMATE-358 ^[3].
• Neoadjuvant chemotherapy (platinum-based) can be considered for selected patients unfit for upfront surgery or primary chemoradiotherapy, with re-staging after 3 to 4 cycles ^[1].
• Palliative care. Early palliative care improves symptom control and end-of-life outcomes and should be offered in distant/inoperable recurrence ^[1].

Vulvar melanoma is very rare (0.1 per 100 000) with a poor prognosis (about 15% 5-year survival for mucosal melanomas) and differs in cause and genetics from cutaneous melanoma ^[3].

• It is the second most common vulvar malignancy and accounts for about 5% of all vulvar cancers ^[3].
• Staging. FIGO staging does not apply; AJCC melanoma staging with Breslow thickness, Clark level, ulceration, and mitotic count is preferred, with only Clark/Breslow microstaging used for vulvar lesions ^[3].
• Treatment. Radical local excision with at least 1 cm margins around the lesion; more conservative resection is increasingly favoured (no survival advantage for radical vulvectomy) ^[3]. Lymph node dissection remains controversial and has shown no overall survival benefit, but sentinel lymph node evaluation is explored though not standard (false-negative rate up to 15%) ^[3]. Mutation testing (c-kit, BRAF) is recommended; nivolumab and other targeted/immunotherapies are potential options ^[1][3].

• Bartholin gland carcinoma, Paget disease, verrucous carcinoma, and sarcoma require individualised specialist MDT management; Page disease of the vulva is often associated with an underlying adenocarcinoma and prolonged follow-up ^[1].
• VIN (pre-malignant) treatment. HSIL: simple excision with around 5 mm margins and 4 mm depth (acceptable response with imiquimod/cidofovir where preferred) with recurrence risk 30 to 40%; close follow-up for 2 to 3 years. dVIN: excision with 0.5 to 1 cm margins (mandatory to exclude invasion). HSIL and dVIN are best managed in clinics skilled in vulval disease ^[3].

• DES daughters should be informed of their exposure; NCI advises annual examination to check for adverse effects, including abnormal cervical cells and clear cell adenocarcinoma, and examination features may suggest DES exposure. No major guideline tailors screening specifically for DES daughters, and the youngest DES daughters, born 1972, are now in midlife; routine breast-cancer screening by age is recommended ^[5].
• The ASCCP (2024) consensus recommends screening of the cervix and vagina for clear cell adenocarcinoma in DES-exposed patients (cytology and hrHPV, cervical and vaginal sampling, annually or at least every 3 years, continuing beyond age 65 and after hysterectomy) on the basis of the 2025-referenced DES data; this is not yet a universal UK recommendation ^[4].
• Treatment of clear cell is stage-directed (surgery for early disease, chemoradiation for advanced), with fertility preservation where feasible; DES-associated lesions have relatively good survival (5-year OS 86.1% in registry data) compared with non-DES clear cell ^[4].
• Women who took DES during pregnancy (DES mothers) need routine, age-appropriate cancer screening; there is no increased risk of any cancer other than the documented modest elevation in breast cancer risk ^[5].

• Disease complications. Local ulceration, pain, bleeding, invasion of urethra/bladder/rectum, ureteric obstruction and hydronephrosis, lymphoedema, distant metastasis, death.
• Treatment complications. Wound infection, sexual dysfunction, psychosexual morbidity, groin lymphoedema (16.7 to 49.2% after inguinofemoral lymphadenectomy; incidence lower with SLN alone or SLN plus RT), premature ovarian failure after pelvic irradiation in younger women, telangiectasia/ulceration/fibrosis after radiotherapy, radiation enteritis/cystitis, and chemotherapy toxicities ^[1].
• Fertility and menopausal. Pelvic radiotherapy in younger women causes premature menopause; topical estrogens and hormone replacement therapy should be considered after treatment ^[1].
• Lymphoedema risk is increased by obesity; patients should be advised on exercise, weight control, prompt treatment of skin infection or bites, and referred to lymphoedema services if affected ^[1].
• Recurrence-related. The same tumour frequently recurs close to its original site if margins are involved; new primaries often arise later in the lichen-sclerosus field ^[3].

• Vulvar cancer recurs in about 33% of women after primary treatment, with a 5-year survival after primary treatment of about 70%; prognosis is least favourable with lymph node involvement ^[1].
• Recurrence rate is 12 to 37%, and most recurrences occur within the first 2 years ^[1]. The risk of local recurrence persists at about 4% per year for local (vulvar) and inguinofemoral/nodal recurrence doubles with primary nodal disease ^[1].
• Vulvar local recurrence is associated with a median disease-free interval of 21 months if it occurs at the primary site versus 69 months if at a new vulvar site in a lichen-sclerosus field; 5-year survival after an isolated vulvar recurrence is about 60% ^[3]. ^[4]
• Isolated inguinofemoral nodal recurrence carries a poor prognosis (5-year survival 0 to 20%) and usually occurs within 2 years ^[1].
• Stage-related (FIGO 2021): from the NCDB, 5-year survival drops from 86.3% in stage IA and 77.1% in stage IB to 64.5% (II), 60.3% (IIIA), 49.6% (IIIB), 31.3% (IIIC), 25.9% (IVA), 18.3% (IVB) (median ages over 60) ^[2].
• Vaginal cancer. Early-stage (I/II) vaginal cancer has 5-year survival up to 80 to 90%; advanced disease ~30%; vaginal clear cell has relatively good survival (5-year OS about 86% in DES-exposed, 81% without, in registry data) ^[4].
• Vulvar melanoma has about 15% 5-year survival for mucosal melanomas ^[3].
• Prognostic factors: nodal status remains the most important; plus HPV status (p16 positive tumours may have better outcomes), tumour size, depth of invasion, LVSI/perineural invasion, and age ^[1][4].

• There is no specific screening for vulvar cancer. Encourage self-examination in women with lichen sclerosus, biopsy of suspicious lesions, and vulval inspection at follow-up of cervical/vaginal/anal SI ^[3].
• Treat lichen sclerosus promptly with ultrapotent steroids and maintenance; sustained control reduces scarring and cancer risk ^[6].
• HPV vaccination reduces HSIL incidence and protects against HPV-driven vulval and vaginal disease (efficacy above 90%) ^[3].
• Counsel on smoking cessation, HIV care, and (for DES daughters) appropriate gynaecological review ^[3][5].

• Pregnancy. Vulvar cancer is rare in pregnancy; care should be individualised by a multidisciplinary team including gynaecological oncology and obstetrics.
• Children. Prepubertal lichen sclerosus is treated with potent topical steroids; vulvar cancer in the young is usually HPV-driven and requires oncology care.
• Older adults. Over one-third of women with vulvar cancer are over 75; frailty, comorbidity, and life expectancy modify both extent of surgery and adjuvant therapy; CGA is advised before extensive evaluation ^[1].
• Immunocompromised women (HIV) have higher HPV-driven disease; treatment paradigms like HSIL in these women lack good evidence ^[3].
• Trans and non-binary patients with female genital tract anatomy should receive the same pathways (cancer reference wording only, general principle).

• Low-cost effective interventions available in almost all settings: punch biopsy of any suspicious persistent lesion is cheap, and must be the cornerstone; the diagnosis is usually clinical with histology ^[3].
• Potent topical steroids (such as clobetasol propionate 0.05%) and moisturisers are the mainstay of lichen sclerosus; treatment sequences as described. ^[6]
• Where sentinel-node mapping, CT/MRI and PET are unavailable, double-incision inguinofemoral lymphadenectomy and basic surgery remain the standard of care, with referral to centres with radiotherapy and surgery where possible.
• Local clinicians should be trained in self-examination, vulval photography, and documentation of nodal status, because early centralisation improves outcomes in rare disease ^[1].

• Vulvar SCC is the commonest vulvar cancer and follows two pathways: HPV-associated (warty/basaloid, younger) and HPV-independent (keratinizing, older, on a background of lichen sclerosus/dVIN) ^[3].
• Incidence is rising in women under 60 (mostly HPV-driven), so vaccinate, screen the vulva in those with SILs, and biopsy new, changing or persistent lesions ^[3].
• Lichen sclerosus carries a lifetime risk of vulvar cancer of about 2 to 5% in affected women, and up to 65% of vulvar cancers have a background of lichen sclerosus; long-term maintenance topical ultrapotent steroids is the cornerstone ^[6].
• dVIN progresses faster than HSIL and must be excised with 0.5 to 1 cm margins ^[3].
• FIGO 2021 staging for vulvar cancer uses two substages in Stage I and defines depth of invasion from the deepest adjacent dysplastic rete ridge; FIGO staging is not used for melanoma ^[2].
• Early vulvar cancer is treated by radical local excision plus SLN mapping (when under 4 cm, invasion greater than 1 mm); micrometastasis 2 mm or less or ITC can be managed with 50 Gy in 25 to 28 fractions instead of full lymphadenectomy ^[1].
• Adjuvant radiotherapy is indicated for close/positive margins, more than one positive node, or extracapsular spread; aim to complete all by 104 days after surgery ^[1].
• Primary chemoradiotherapy (cisplatin 40 mg/m2 weekly with 57.6 to 70 Gy) is for unresectable disease ^[1].
• Vaginal cancer is clinically staged like cervical cancer and treated chiefly by radiotherapy, with surgery reserved for selected early-stage disease; chemoradiation improves survival in large retrospective series ^[4].
• Clear cell adenocarcinoma is caused by in-utero DES exposure; DES daughters have ~40 times the risk, though it is still rare (~1 per 1,000); risk is highest when exposure occurred in the first 16 weeks of gestation ^[5][4].
• Early vulvar recurrence carries a relatively good prognosis if managed aggressively; remote-site disease suggests field cancerisation and needs long-term follow-up ^[1][3].

Vulvar and vaginal cancer connects to abnormal uterine bleeding (postmenopausal bleeding evaluation), cervical cancer and screening, cervicitis and pelvic inflammatory disease, menopause and hormone therapy, polycystic ovary syndrome (anovulation and hyperplasia context), drugs and teratogens in pregnancy (DES exposure), contraception, lichen sclerosus management, melanoma and skin cancer, radiation oncology principles, pelvic exenteration, lymphoedema management, and psychosexual counselling. These are listed as plain text while their pages are being verified.