Vulvar disease

Vulvar disease refers to disorders of the vulvar skin, mucosa and appendages, including infectious and inflammatory dermatoses, lichen sclerosus and lichen planus, vulvar intraepithelial neoplasia, benign cysts and vulvar cancer, and chronic vulvar pain. The lesions affect urination, sexual function, clothing comfort and psychological state, and shame and misdiagnosis often delay presentation. Vulvar cancer accounts for about 2% to 5% of gynaecological malignancies, lichen sclerosus has a lifetime risk of about 0.1% to 0.3% in women, and vulvodynia affects 3% to 15% of women in different populations.

Terminology and classification

• The vulva includes the mons pubis, labia majora, labia minora, clitoris, vestibule, Bartholin glands and perineum, and localisation is the basis of classification and treatment.
• The International Society for the Study of Vulvovaginal Disease classifies vulvar disease by cause into infection, inflammatory dermatosis, premalignant lesion, malignancy, cyst and pain syndrome, and several categories may coexist.
• Lichen sclerosus is a chronic inflammatory dermatosis and is not equivalent to leukoplakia, which is only a morphological description and requires distinction from lichen planus, vitiligo and lichen simplex chronicus.
• Vulvar intraepithelial neoplasia uses a two-tier low-grade and high-grade system, and high-grade lesions are divided into usual type, mostly related to high-risk human papillomavirus, and differentiated type, often arising in chronic inflammation such as lichen sclerosus.
• About 90% of vulvar cancers are squamous cell carcinomas, with basal cell carcinoma, adenocarcinoma, melanoma and sarcoma making up the rest, and histology determines surgical margins and nodal management.
• Two carcinogenic pathways exist, one driven by high-risk human papillomavirus in younger women and the other related to chronic inflammation and lichen sclerosus in older women, with different molecular features and prognosis.
• ICD-10 places vulvitis, vulvar cysts and other vulvar disease at N75 to N90 and vulvar cancer at C51, while premalignant lesions require morphological codes.
• ICD-11 groups vulvar disease within genitourinary disease and subdivides by inflammation, tumour and pain, and cross-version conversion requires official mapping.
• MeSH uses D014846 for vulvar diseases, and retrieval must add lichen sclerosus, vulvodynia and vulvar neoplasm to avoid vaginal and cervical entries.
• The 2015 international consensus defined vulvodynia as vulvar pain lasting at least three months and divided it into provoked, spontaneous and mixed types after excluding other causes.
• Older terms such as vulvar vestibulitis and vulvar vestibulitis syndrome have been replaced by terminology emphasising mechanism and multifactorial origin, although the old names persist in highly cited literature.
• Vulvovaginal candidiasis is an infectious vulvar disease distinct from dermatoses, and diagnosis requires mycological evidence rather than itching alone.
• Bartholin duct cyst and abscess are ductal obstruction disorders with a different pathway from dermatoses and tumours, and anatomical origin should be stated.
• Chinese literature often uses the umbrella term white lesions of the vulva, which covers lichen sclerosus, lichen planus and lichen simplex chronicus and is no longer used as a modern diagnostic label.

History

• In 1912 Bowen described a red scaly precancerous dermatosis later called Bowen disease, an early source for the concept of vulvar intraepithelial neoplasia.
• In the late nineteenth and early twentieth centuries vulvectomy was reserved for advanced cancer, and the operation was extensive with high morbidity and limited survival gain.
• In the mid-twentieth century radiotherapy was used for local control of vulvar cancer, but poor tissue tolerance and radiation dermatitis gradually favoured surgery.
• In the 1970s and 1980s the concept of vulvar intraepithelial neoplasia was established, and recognition that not all lesions progress led to criticism of extensive excision.
• In the 1980s zur Hausen and colleagues established the link between high-risk human papillomavirus and lower genital tract cancer, and vulvar cancer was reclassified into viral and non-viral types.
• In the 1990s wide local excision with inguinal lymphadenectomy became standard, but the morbidity of nodal dissection prompted sentinel node development.
• In 2008 the GROINSS-V study showed that sentinel node biopsy could replace systematic inguinal dissection in early vulvar cancer and substantially reduced lymphoedema in node-negative patients.^[1]
• In 2012 the International Society for the Study of Vulvovaginal Disease updated recommendations for lichen sclerosus, emphasising lifelong follow-up and cancer surveillance.
• In 2015 the International Society for the Study of Vulvovaginal Disease with the International Society for the Study of Women's Sexual Health and the International Pelvic Pain Society published consensus terminology for vulvodynia.^[2]
• In 2016 vulvodynia entered the chronic pain entries of ICD-11 and gained a separate code and research agenda.
• In 2018 the European Dermatology Forum published guidance for vulvar lichen sclerosus and established super-potent topical corticosteroids as first-line therapy.
• In 2021 the International Federation of Gynaecology and Obstetrics updated vulvar cancer staging to emphasise tumour size, nodal status and metastatic extent.^[3]
• In the 2020s immune checkpoint inhibitors and molecular subtyping entered practice, and differences between human papillomavirus-related and p53-abnormal tumours became a research focus.
• From radical excision to organ-sparing surgery and molecular classification, the history reflects a continuing rebalancing of cancer control and quality of life.

Epidemiology

• Vulvar cancer accounts for about 2% to 5% of female reproductive malignancies, with an estimated 47000 new cases and 17000 deaths worldwide in 2022, and incidence is rising in low-income countries.^[4]
• Lichen sclerosus has a lifetime risk of about 0.1% to 0.3% in women, occurs at any age with peaks before puberty and after menopause, and childhood cases are often misdiagnosed as abuse or eczema.
• Vulvodynia affects 3% to 15% of women in general populations and more in gynaecology clinics, with a course often lasting years and major effects on sexual function and mental health.
• Vulvovaginal candidiasis affects about 75% of women at least once, and 5% to 8% develop recurrent infection with four or more episodes per year.
• High-grade vulvar intraepithelial neoplasia has increased over three decades, with human papillomavirus-related disease in younger women and differentiated disease in older women.
• Vulvar cancer has a bimodal age distribution, with human papillomavirus-related disease at 40 to 60 years and non-viral disease after 70 years, often with lichen sclerosus.
• Risk factors include at least high-risk human papillomavirus, smoking, immunosuppression, chronic lichen sclerosus, older age, obesity, diabetes and autoimmune disease such as multiple sclerosis.
• Smoking interacts with human papillomavirus to increase vulvar intraepithelial neoplasia and cancer risk, and cessation lowers but does not abolish progression.
• Immunosuppression from human immunodeficiency virus, transplant therapy and autoimmune treatment makes premalignant lesions more common and more recurrent.
• Nodal metastasis correlates with tumour size and depth of invasion, and sentinel node positivity is below 10% in tumours smaller than 2 cm with shallow invasion.
• Geography affects the proportion of human papillomavirus-related disease, which is lower in North America and Europe and higher in some developing countries.
• Costs include repeated visits, pathology, medication and lost work, and the indirect cost of vulvodynia is particularly high.
• Psychosocial burden is underestimated, as itching, pain and appearance change cause shame, avoidance of intimacy and depression, with delay of years before presentation.
• Older women and children experience the longest delays, because symptoms are attributed to ageing in the former and examination is limited in the latter.

Pathophysiology

• Lichen sclerosus involves autoimmunity, genetic susceptibility and local oxidative stress, and HLA-DQ7 and family clustering suggest immunogenetic contributions.
• Histology shows epidermal atrophy, basal cell liquefaction and homogenisation of superficial dermal collagen, with inflammation and vascular change producing itch and fissuring.
• Vulvar lichen planus is a T-cell mediated interface dermatitis with band-like lymphocytic infiltration and basal damage, presenting as purple polygonal papules and erosions.
• Human papillomavirus-related vulvar cancer shares the mechanism of other lower genital tract tumours, in which E6 and E7 degrade p53 and retinoblastoma protein and drive cell cycle loss of control.^[5]
• Non-viral vulvar cancer often carries p53 mutation and chronic inflammation, and differentiated vulvar intraepithelial neoplasia is its precursor with faster progression.
• Lymphatic drainage runs first to superficial inguinal nodes, and tumour site and size determine the route, which underpins sentinel node techniques.
• Vulvodynia is multifactorial, involving peripheral nerve proliferation, central sensitisation, pelvic floor hypertonicity and psychological factors, and no single mechanism explains all symptoms.
• Vestibular inflammation and mast cell infiltration are repeatedly reported in vestibulodynia, but causality is unclear and neuroimmune interaction is the current focus.
• Recurrent vulvovaginal candidiasis involves host immunity, vaginal flora imbalance and fungal biofilm, which resists clearance by conventional antifungals.
• Malignant transformation of lichen sclerosus occurs in about 2% to 5%, with higher risk in untreated or poorly controlled disease, and follow-up biopsy is key to early detection.
• Atrophy and adhesion can cause labial fusion, buried clitoris and urethral narrowing, further worsening urination and dyspareunia.
• Surgery and radiotherapy cause lymphoedema, scar contracture and sexual dysfunction as long-term structural consequences.
• In older women the skin barrier declines and oestrogen deficiency thins the epithelium, raising the risk of infection and contact dermatitis.
• Childhood vulvar disease differs from adult disease, with low oestrogen, hygiene and congenital anatomy as the main considerations.

Clinical features

• Itching is the most common symptom of vulvar dermatoses, and lichen sclerosus itch is often worse at night with burning, and scratching produces fissures and secondary infection.
• Pain may be constant, burning or provoked, and vulvodynia worsens with contact, intercourse, cycling or tight clothing, with severity often discordant with signs.
• Appearance changes include white patches, thin papery skin, wrinkling, fissures, purple papules and erosions, often described by patients as white spots or hardening.
• A vulvar mass may be a cyst, abscess, fibroma or cancer, and a hard fixed mass with a non-healing ulcer requires exclusion of malignancy.
• Bleeding and discharge suggest ulceration, infection or tumour, and postmenopausal bleeding requires vulvar and vaginal assessment even when scanty.
• Dyspareunia and reduced libido are the most neglected consequences, and clinicians should ask directly because shame prevents disclosure.
• Complications include at least scarring and adhesion, labial fusion, urethral narrowing, secondary infection, malignant transformation, sexual dysfunction and psychological disorder.
• Nodal metastasis presents as an inguinal mass, and advanced disease can invade urethra, vagina and rectum and form fistulae.
• Vulvodynia often coexists with pelvic floor dysfunction, overactive bladder and irritable bowel symptoms, suggesting central sensitisation and multisystem overlap.
• Presentations differ by group, with itching, scratching and dysuria in children, candidiasis and varicosities in pregnancy and atrophy, lichenification and tumour in older women.
• Death from vulvar cancer follows nodal and distant spread, and five-year survival is 70% to 90% in early disease and 30% to 50% with nodal involvement.
• Chronic itch and pain cause sleep disturbance, inattention and social withdrawal, with quality of life well below general population norms.
• Signs are often masked by self-treatment with washes and creams, so all topical products should be recorded to avoid mistaking contact dermatitis for primary disease.
• The classic figure-of-eight white plaque surrounds the vulva and perianus in lichen sclerosus, but atypical cases may show only fissures or erythema.

Diagnosis

• Diagnosis begins with a detailed history of symptom duration, triggers, topical products, sexual history, skin disease and autoimmunity, obtained in privacy.
• Vulvar examination requires good lighting and full exposure to inspect colour, texture, fissures, ulcers and masses, with palpation of inguinal nodes.
• Vulvoscopy magnifies epithelial and vascular patterns and guides biopsy, but does not replace histopathology.
• Histopathology confirms lichen sclerosus, lichen planus, intraepithelial neoplasia and cancer, and a single negative biopsy does not exclude early disease.
• The 2015 consensus defines vulvodynia clinically after exclusion of other causes, and biopsy is reserved for suspected alternatives.
• Vulvar cancer is staged by the 2021 International Federation of Gynaecology and Obstetrics system using tumour size, nodal status and distant spread.
• Ultrasound assesses inguinal nodes, magnetic resonance imaging evaluates local invasion and pelvic disease, and positron emission tomography screens for distant metastasis.
• Sentinel node biopsy suits early unifocal tumours smaller than 4 cm with clinically negative nodes and reduces the morbidity of systematic dissection.
• Laboratory tests include fungal microscopy and culture, human papillomavirus testing, syphilis serology and herpes simplex polymerase chain reaction.
• Differential diagnosis includes at least vulvovaginal candidiasis, contact dermatitis, vulvar lichen planus, psoriasis, vitiligo, vulvar cancer, Bartholin cyst, herpes simplex and syphilis.
• Contact dermatitis often follows washes, wipes, condoms or drugs, and improvement after withdrawal is an important clue.
• Vulvar psoriasis may lack typical scale, so scalp, nail and truncal lesions should be assessed.
• Cancer and lichen sclerosus can coexist, and thickening, nodules or non-healing ulcers in lichen sclerosus require prompt biopsy.
• Diagnostic delay of years is common because of shame, limited clinician training and non-specific symptoms.
• No population screening programme exists, and opportunistic detection depends on visual inspection during gynaecological examination and targeted follow-up of high-risk women.

Management

• Treatment aims to relieve symptoms, restore the skin barrier, prevent cancer, preserve sexual function and improve quality of life, and must be individualised.
• First-line therapy for vulvar lichen sclerosus is a super-potent topical corticosteroid, with clobetasol propionate ointment once daily for induction and then a tapering maintenance schedule.
• Calcineurin inhibitors such as tacrolimus and pimecrolimus are second-line or alternatives for steroid intolerance, but cancer surveillance must continue.
• Vulvar lichen planus is treated with potent topical steroids, erosive disease may need short systemic steroids or immunosuppression, and long-term mucosal surveillance is required.
• Vulvodynia uses multimodal care including pelvic floor physical therapy, cognitive behavioural therapy, topical anaesthetics, tricyclic antidepressants and gabapentinoids.
• Acute vulvovaginal candidiasis is treated with topical azoles or single-dose oral fluconazole, and recurrent disease needs induction followed by maintenance and host factor assessment.
• Asymptomatic Bartholin cysts may be observed, while recurrent abscess requires marsupialisation rather than simple incision to preserve gland function.
• High-grade vulvar intraepithelial neoplasia may be treated by local excision, laser ablation, imiquimod or 5-fluorouracil according to extent, multifocality and fertility plans.
• Vulvar cancer is managed surgically, with wide local excision and sentinel node biopsy for early disease and inguinal dissection or chemoradiotherapy for nodal involvement.
• Locally advanced disease receives concurrent chemoradiotherapy, and recurrent or metastatic disease may receive checkpoint inhibitors or targeted therapy, with better response in human papillomavirus-related tumours.
• Radiotherapy is used postoperatively in high-risk patients and for inoperable disease, and intensity-modulated techniques reduce radiation dermatitis in poorly tolerant vulvar skin.
• Prevention includes human papillomavirus vaccination, smoking cessation, avoidance of irritants, vulvar hygiene and prompt treatment of chronic dermatoses.
• Lichen sclerosus requires lifelong follow-up every 6 to 12 months with biopsy of thickening or ulceration, and cancer surveillance is central.
• Prognosis varies, with lichen sclerosus usually controllable but relapsing, vulvodynia chronic and fluctuating and vulvar cancer survival dependent on stage and nodal status.
• A multidisciplinary team includes gynaecology, dermatology, pathology, oncology, radiation oncology and psychological support, and complex decisions should integrate all views.

Research and controversies

• Autoimmunity and the microbiome in lichen sclerosus are active areas, but causality and actionable targets remain unsettled and local microbiome therapy is exploratory.
• Classification and diagnostic criteria for vulvodynia remain debated, with some favouring neuropathic and inflammatory stratification and others emphasising psychological and pelvic floor factors.
• Indications for sentinel node biopsy in vulvar cancer are disputed, especially for tumours larger than 4 cm or multifocal disease, and the meaning of micrometastasis is unclear.
• Differences between human papillomavirus-related and non-related vulvar cancer are under study, and immunotherapy benefit in non-related disease is limited, making biomarker selection a priority.
• Overtreatment of vulvar intraepithelial neoplasia is a concern, as low-grade lesions in young women may regress, and conservative observation competes with excision.
• Radiotherapy optimisation and organ preservation are difficult, and intensity modulation and sentinel node guided radiotherapy are changing practice.
• The central sensitisation hypothesis has driven drug research in vulvodynia, but trials are small with inconsistent endpoints and low evidence grades.
• Long-term outcomes of childhood lichen sclerosus are lacking, and rates of remission and relapse after puberty and cancer risk compared with adults remain unknown.
• Guideline disagreement centres on biopsy timing, steroid duration and nodal management, and European and American recommendations differ in several areas.
• Stigma and inadequate medical education cause delayed presentation, and whether vulvar examination should be part of routine screening is a public health debate.
• Digital health and remote consultation may improve follow-up access, but visual assessment of vulvar lesions usually needs specialist examination and limits remote care.
• Unmet needs include targeted therapy for lichen sclerosus, biomarkers for vulvodynia, organ-sparing options for vulvar cancer and devices adapted to children and older women.