Vulval cancer and vaginal cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Vulval squamous cancer develops through two main routes. HPV-associated disease often occurs with multifocal HSIL, smoking and immune suppression. HPV-independent disease is linked to lichen sclerosus and differentiated VIN and can progress rapidly from a subtle thickened or eroded focus. Persistent symptoms need direct inspection under good light; a new focal change within a chronic dermatosis is not assumed to be another flare.

Biopsy should diagnose without compromising definitive anatomy. Lesion mapping records size, depth estimate and relation to midline, clitoris, urethra, vagina and anus. MRI defines deeper extension and CT or PET-CT assesses nodes and distant disease. Groin-node assessment is crucial: sentinel biopsy reduces lymphoedema and wound morbidity for eligible small unifocal disease, while suspicious nodes undergo ultrasound-guided sampling and treatment planning.

Vaginal cancer is much rarer and must be distinguished from cervical, endometrial or vulval extension. HPV-associated squamous carcinoma is commonest, while clear-cell adenocarcinoma is a rare DES-related entity. MRI maps vaginal level and pelvic-organ invasion. Lymph drainage changes from pelvic in upper vagina to inguinal in the lower third, so treatment fields are site specific. Definitive external-beam radiation plus brachytherapy preserves anatomy for most cases.

Treatment must address function. Radical local vulval excision preserves tissue while achieving margins; primary chemoradiation can avoid major exenteration. Groin surgery and radiation create substantial lymphatic risk, and perineal wounds can break down or infect. Vaginal radiation causes stenosis and sexual pain. Specialist nursing, pelvic-floor therapy, dilator support, lymphoedema prevention and trauma-informed sexual care are part of oncological quality.

Key points

Persistent vulval itch, soreness, ulcer, lump or architectural change requires examination and a punch or incisional biopsy; repeated antifungal or steroid treatment must not delay tissue.
Most vulval cancer is squamous: one pathway is HPV related, while the other arises through lichen sclerosus and differentiated VIN with p53 abnormalities.
Map and biopsy the lesion before wide excision so depth, histology, relation to clitoris, urethra and anus and the correct nodal plan can be agreed.
MRI pelvis is preferred for local extension in larger vulval and vaginal cancer; CT or PET-CT assesses groin, pelvic nodes and distant spread according to stage.
For unifocal vulval SCC smaller than 4 cm, more than 1 mm invasive and with clinically and radiologically negative groins, sentinel-node biopsy is the preferred low-morbidity nodal staging option.
Midline or near-midline vulval lesions can drain bilaterally and require a bilateral sentinel or groin strategy; a positive sentinel result enters burden-specific groin treatment.
Early vulval cancer is treated by radical local excision with adequate pathological margins rather than routine radical vulvectomy, preserving uninvolved anatomy.
Locally advanced vulval cancer may receive primary chemoradiation to avoid exenterative surgery, with biopsy-confirmed residual disease considered for salvage.
Primary vaginal cancer is rare and is diagnosed only after excluding cervical and vulval origin; definitive radiotherapy with brachytherapy is central for most invasive disease.
Small superficial upper-vaginal tumours may be surgically treated in selected patients, but level, prior hysterectomy and organ relationships demand specialist planning.
Treat lichen sclerosus effectively with potent topical corticosteroid and lifelong self-examination and review; symptom improvement does not remove the need to biopsy a new focal lesion.
Imiquimod is a specialist option for selected HPV-associated vulval HSIL, not for suspected invasive cancer or differentiated VIN.
Plan wound, lymphatic, urinary, bowel, sexual, vaginal-dilator and psychological rehabilitation before treatment.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

High-risk HPV pathway

Persistent oncogenic HPV causes vulval and vaginal high-grade squamous intraepithelial lesions and cancer, particularly with smoking, HIV or other immunosuppression.

Lichen sclerosus and differentiated VIN

Chronic vulval inflammatory dermatosis and p53-abnormal differentiated intraepithelial neoplasia drive HPV-independent squamous cancer, often in older patients.

Previous lower-genital-tract neoplasia

Cervical, vaginal or vulval HSIL and prior cervical cancer identify a multicentric HPV field and increase later vaginal-cancer risk.

Rare exposure and histology

In-utero diethylstilbestrol exposure is linked to vaginal clear-cell adenocarcinoma, while melanoma, Paget disease, sarcoma and glandular tumours have separate causes.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Precursor epithelium becomes invasive
HPV E6 and E7 or p53-driven differentiated VIN permits atypical squamous cells to cross the basement membrane and infiltrate vulval or vaginal stroma.
2
Vulval lymph follows groins
Most invasive vulval cancers spread first to superficial and deep inguinofemoral nodes, with bilateral risk increasing near the midline.
3
Vaginal drainage depends on level
Upper-vaginal tumours drain to pelvic nodes, while lower-third lesions can reach inguinal nodes, determining radiation fields and nodal assessment.
4
Local extension threatens function
Tumour can involve clitoris, urethra, vagina, anus, bladder and rectum, causing pain, bleeding, fistula and major sexual and excretory morbidity.
5
Radiation response enables preservation
External-beam and brachytherapy can sterilise vaginal and advanced vulval tumour while avoiding exenterative surgery, but cause mucosal, skin and fibrotic late effects.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

HPV-related vulval disease

Multifocal warty, pigmented or erythematous HSIL in a younger or immunosuppressed patient can coexist with an invasive focus.

Differentiated vulval pathway

A solitary thick, keratotic, eroded or ulcerated area within pale lichen sclerosus in an older patient needs urgent biopsy.

Vaginal cancer

Bleeding, watery discharge, dyspareunia or a vaginal-wall mass after exclusion of cervical and vulval origin supports a primary vaginal tumour.

Groin nodal disease

A firm enlarged inguinal node may be regional metastasis and requires imaging and needle sampling before definitive treatment.

Advanced local invasion

Urethral or anal fixation, fistula, retention, hydronephrosis, severe pain or pelvic sidewall involvement indicates complex locally advanced disease.

Necrotising infection or haemorrhageRed flag

Crepitus, spreading erythema, shock, severe disproportionate pain or brisk bleeding requires immediate resuscitation and source control.

Red flags requiring action

Persistent vulval itch, soreness, ulcer, lump, colour or texture change requires visual examination and biopsy rather than repeated empirical antifungal treatment.
A hard fixed vulval lesion, enlarged groin node, clitoral or urethral involvement or severe focal pain suggests invasive disease.
Postcoital or postmenopausal bleeding, watery discharge, vaginal mass or dyspareunia requires speculum examination and directed biopsy.
Fever, crepitus, spreading perineal erythema, severe pain out of proportion or systemic toxicity suggests necrotising or deep infection.
Urinary retention, hydronephrosis, rectal symptoms, fistula or pelvic sidewall pain suggests locally advanced vaginal or vulval cancer.
A new ulcer or nodule within lichen sclerosus or differentiated VIN needs prompt re-biopsy even if the inflammatory disease is under treatment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line complete vulvovaginal examinationFirst stepFirst line
Why
Map lesion number, size, site, colour, texture and relation to clitoris, urethra, vagina, anus and groin nodes.
Interpretation and limitations
Use vulvoscopy, speculum and bimanual examination and document a diagram or photograph with consent; examine cervix and anus for multicentric HPV disease.
02
Reference punch or incisional biopsy
Why
Establish invasion, depth, histological type and HPV-associated versus differentiated precursor context before definitive excision.
Interpretation and limitations
Sample the most suspicious thickened, ulcerated or pigmented focus, use separate labelled biopsies for multifocal disease and repeat if tissue does not explain the lesion.
03
Preferred pelvic MRIPreferred
Why
Define tumour depth, vagina, urethra, anus, bladder, rectum, pelvic sidewall and nodes for surgery and radiotherapy.
Interpretation and limitations
MRI supports but does not replace examination; post-biopsy inflammation and small superficial lesions can be difficult to characterise.
04
CT or PET-CT staging
Why
Assess inguinal and pelvic nodes, lung, liver, bone and other distant disease in higher-risk or advanced cancer.
Interpretation and limitations
Inflammatory groin nodes can be avid; sample a management-changing suspicious node with ultrasound-guided core or FNA where feasible.
05
Sentinel-node mapping for eligible vulval SCC
Why
Stage clinically negative groins with less wound and lymphoedema morbidity than full inguinofemoral dissection.
Interpretation and limitations
Restrict to unifocal tumours under 4 cm with invasion beyond 1 mm and no suspicious nodes; midline proximity requires bilateral drainage assessment.
06
HPV and immune-health assessment
Why
Identify associated cervical, anal or vaginal neoplasia, HIV and modifiable immune or smoking factors.
Interpretation and limitations
HPV association can be supported by p16, but histology and invasion govern treatment; HIV positivity does not automatically remove curative intent.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Inflammatory dermatosis

Lichen sclerosus, lichen planus, dermatitis and psoriasis cause itch and texture change; biopsy confirms uncertain, thickened, eroded or treatment-resistant areas.

Infection

Candidiasis, herpes, syphilis and bacterial disease cause irritation, ulceration or discharge, but positive microbiology does not explain a persistent indurated lesion automatically.

Benign cyst and gland disease

Bartholin cyst, hidradenitis and inclusion cyst can form lumps; a new Bartholin-region mass in an older patient requires malignancy assessment.

Melanoma or Paget disease

Pigmented, amelanotic or eczematous vulval lesions may be melanoma or extramammary Paget and need immunohistochemical classification before SCC treatment.

Cervical or endometrial primary

A tumour extending into vagina from cervix or uterus is staged and treated from its primary site; examination and imaging must establish origin.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Persistent lesionBiopsy before repeated empirical treatmentFirst stepVulval or vaginal itch, pain, bleeding, ulcer, lump or texture change persists or recurs.

1Perform a complete trauma-informed vulval, vaginal, cervical, anal and groin examination and assess infection, immune suppression and lichen-sclerosus history.
2Obtain one or more labelled punch or incisional biopsies from the most suspicious areas before ablation, imiquimod or wide excision.
3Once invasion is proven, obtain MRI and nodal or distant staging appropriate to site and refer to the specialist gynaecological oncology MDT.

02Early vulval SCCExcise locally and stage groins selectivelyInvasive squamous cancer is small, unifocal and resectable without major organ sacrifice.

1Plan radical local excision around clitoris, urethra and anus with reconstructive input where needed and avoid removing uninvolved vulva routinely.
2Use sentinel-node biopsy for an eligible tumour with negative groins and choose unilateral or bilateral mapping from distance to midline and drainage.
3Review depth, margins, lymphovascular invasion and sentinel burden and use re-excision, groin treatment or radiation according to recurrence risk.

03Advanced vulvalCompare chemoradiation with radical surgeryTumour involves urethra, anus, vagina, fixed nodes or other anatomy that would require highly morbid resection.

1Obtain MRI, PET-CT and biopsy of suspicious nodes, optimise wounds, infection, nutrition and pain and review resectability with reconstructive and pelvic teams.
2DefinitiveUse definitive chemoradiation when organ preservation and control are plausible or select radical surgery within an expert exenterative pathway when it offers better clearance.
3Allow post-radiation response to mature, biopsy suspicious residual disease and plan salvage, lymphatic, wound and functional rehabilitation.

04Vaginal cancerTreat by level, histology and adjacent organsBiopsy confirms a primary vaginal malignancy after cervical and vulval origin are excluded.

1Map upper, middle or lower-third disease with MRI and CT or PET-CT and define pelvic versus inguinal nodal risk and bladder and rectal relationships.
2Use external-beam radiation with image-guided brachytherapy for most invasive squamous cancers, adding radiosensitising cisplatin when appropriate.
3Reserve surgery for selected small superficial lesions or salvage and provide vaginal, sexual, bowel, urinary and lymphoedema rehabilitation from the outset.

05Field diseaseControl precursor and inflammatory risk lifelongHPV-associated HSIL, differentiated VIN or lichen sclerosus accompanies or precedes cancer.

1Treat lichen sclerosus with an adequate potent topical corticosteroid regimen and educate about self-examination and new focal warning signs.
2Use excision, laser or specialist imiquimod for selected vulval HSIL only after invasion has been excluded; differentiated VIN generally requires excision.
3Continue lifelong vulval review and site-appropriate cervical, vaginal and anal surveillance, smoking support and immune-health optimisation.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Radiosensitises selected locally advanced vulval and primary vaginal squamous cancers during definitive organ-preserving radiation and brachytherapy.

Cisplatin with definitive radiotherapy

Give cisplatin 40 mg/m² intravenously once weekly during external-beam radiotherapy, often for five or six doses, using the exact centre hydration, renal and dose-cap protocol.

Monitor creatinine clearance, magnesium, marrow, hearing, neuropathy, hydration and infection and do not compromise timely brachytherapy merely to deliver another cisplatin dose.

Controls vulval inflammation, symptoms, scarring and part of the cancer risk associated with undertreated lichen sclerosus field disease.

Clobetasol propionate for lichen sclerosus

Apply clobetasol propionate 0.05% ointment thinly once nightly for 4 weeks, then on alternate nights for 4 weeks, then twice weekly for 4 weeks before review and individual maintenance.

Demonstrate the small amount and correct sites, review response and maintenance and biopsy any persistent thickened, eroded, ulcerated or new focal area rather than escalating steroid blindly.

Stimulates local innate immunity and can clear selected multifocal HPV-associated vulval HSIL while preserving anatomy.

Imiquimod for selected vulval HSIL

Use imiquimod 5% cream in a specialist off-label protocol, often beginning one to three nights weekly and titrating over approximately 16 weeks according to local reaction and response.

Exclude invasion first and do not use for differentiated VIN or invasive cancer; pain, ulceration and systemic symptoms can require treatment breaks and non-response needs repeat biopsy or excision.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pain, bleeding and infection

Ulceration and necrosis cause severe vulval pain, malodour, discharge, cellulitis, anaemia and difficulty sitting, walking or passing urine.

Groin nodal progression

Metastatic inguinofemoral nodes can ulcerate, infect, compress vessels and cause persistent lower-limb lymphoedema, strongly affecting function and prognosis.

Fistula and organ obstruction

Advanced vaginal or vulval disease can create vesicovaginal or rectovaginal fistula, ureteric obstruction, retention and pelvic sepsis.

Treatment-related lymphatic and sexual harm

Groin surgery and radiation can cause lymphocyst, wound breakdown, lymphoedema, stenosis, dryness, dyspareunia, altered sensation and substantial body-image distress.

Field recurrence and second HPV cancer

Persistent dermatosis, differentiated VIN and multicentric HPV disease create ongoing local recurrence and cervical, anal or other anogenital cancer risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

After vulval surgery, monitor wound separation, infection, flap perfusion, urinary and bowel function, pain, groin lymphocyst and lower-limb lymphoedema.
During chemoradiation, review blood count, renal function, hydration, diarrhoea, urinary symptoms, pain and perineal and groin skin at least weekly.
After vaginal radiation, assess stenosis, dryness, bleeding, dyspareunia, bowel, bladder, pelvic-floor and lymphatic function and provide dilator and sexual support.
Examine vulva and groins at follow-up and biopsy a new or persistent focal lesion rather than diagnosing scar, dermatosis or radiation change by appearance alone.
Track lichen-sclerosus symptom control, steroid technique, scarring and adherence and maintain lifelong patient self-examination and clinical review.
For HPV-related field disease, complete cervical and anal assessment according to risk, smoking cessation and HIV or immune-health care.
Investigate new leg swelling, groin mass, pelvic pain, urinary obstruction, fistula or bleeding promptly for recurrence and thrombosis.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Itch can be the cancer symptom

Vulval SCC often follows months of pruritus or soreness before a dramatic mass appears, making direct inspection essential.

Biopsy location matters

Sampling the thickest edge of an ulcer or the most atypical focus improves detection of invasion compared with necrotic centre alone.

Groin drainage crosses the midline

A tumour close to vulval midline can drain bilaterally even when most of the visible lesion lies on one side.

Vaginal cancer is a diagnosis of origin

Extension from cervix, endometrium or vulva is more common than a primary vaginal tumour and retains the originating cancer’s staging.

Lichen treatment and biopsy coexist

Potent steroid protects the inflammatory field, but a focal non-responsive change still needs tissue rather than stronger empirical treatment.

Function belongs in margin planning

A clear margin must be balanced with clitoral, urethral and anal function through specialist reconstruction, not achieved by indiscriminate radical vulvectomy.

11Common pitfallsFrequent interpretation and management errors.

01
Treating persistent vulval itch repeatedly as candidiasis without examination and biopsy.
02
Performing a wide unplanned excision before depth, anatomy and groin strategy are known.
03
Using imiquimod for a lesion in which invasion or differentiated VIN has not been excluded.
04
Performing routine radical vulvectomy when radical local excision can obtain adequate margins.
05
Using sentinel-node biopsy outside the eligible unifocal, under-4-cm, node-negative setting.
06
Staging a midline vulval lesion with unilateral groin assessment only.
07
Calling vaginal extension a primary vaginal cancer without establishing origin.
08
Omitting brachytherapy from a definitive vaginal-radiation plan.
09
Failing to treat lichen sclerosus or re-biopsy a new focal change.
10
Ignoring wound, lymphoedema, sexual and urinary function after apparently successful treatment.