vulval carcinoma

source; BGCS,SLCOG

Vulval Carcinoma is uncommon,crude incidence rate of 3.9/100 000.

It’s a disease of the old.

rates rise gradually from around age 35–39, and more sharply from around age 65–69,
reaching the highest rates in the 90+ age group.

The most common type of vulval cancer is squamous cell carcinoma (VSCC).

This may be HPV-independent, developing on a background of vulval dermatoses (lichen sclerosus and lichen planus) and differentiated vulval intraepithelial neoplasia (dVIN) or it may HPV-dependent with a background of usual type vulval intraepithelial neoplasia (uVIN).

Risk Factors

1. Smoking
2. Immunosuppression.
3. Advanced age
4. Paget’s disease
5. Melanoma in situ
6. Lichen sclerosus: 4–7% risk of developing cancer
7. Vulval cancer develops in 9% of women with untreated high‐grade VIN, 1–8 years after their VIN diagnosis
   Association with CIN and Cervical Cancer

Types

1. Squamous cell-most common 90%
   Melanoma-2nd most
2. Basal Cell
3. Verrucous CA- type of SCC
4. Pagets disease of vulva
5. Adenocarcinoma
6. Bartholin gland carcinoma

Sites

1. Labium majus-most common 50%
2. Labium minus
3. Clitoris
4. Bartholin’s gland – have adenocarcinomas.
   • Spread
   • Direct extension to adjacent tissues
   • Lymphatic embolization
   • Lymphatic spread – local inguinal—-femoral—common iliac
   • Hematogenous – rare
     IF the lesion is more close to the clitoris, may bypass the inguinal region and go straight to iliac nodes

Prevention, screening, presentation and diagnosis

Prevention and treatment of pre-disposing conditions

HPV Vaccination

The majority of HPV-related VSCC is caused by HPV16.

Prophylactic vaccination against HPV6, 11, 16 and 18 has been shown to result in a substantial
decrease.

usual /classical VIN

World Health Organisation (WHO) and ISSVD refers to LSIL (low-grade squamous intraepithelial lesion that includes HPV-related changes and VIN1) and HSIL (high-grade squamous intraepithelial lesion, which encompasses VIN2, VIN3).

This lesion is characterized by cytological atypia, mitoses extending beyond middle thirds of the epithelium and lack of maturity of the squamous cells with or without associated stigmata of HPV infection such as koilocytosis.

Differentiated VIN

This is an HPV independent lesion that is often seen in older women on a background of lichen
sclerosus. It is characterised by basal cell atypia and abnormal keratinocyte differentiation.
Differentiated VIN is typically associated with p53 mutations.

Other putative precursors
Vulvar acanthosis with altered differentiation (VAAD) is a non-invasive squamous proliferation that may be a precursor to verrucous carcinoma.

Treatment of uVIN

Imiquimod, Cidofovir and surgical excision are treatment options for high
grade VIN all with ~50% response/recurrence rates by 12 months’ post treatment.

However, cidofovir is currently unlicensed for use in uVIN.-(A)

Women with multi-focal HPV related disease should be followed up
colposcopy of the lower genital tract and digital ano-rectal examination with
prompt referral should symptoms of anal cancer develop.

Women with high grade uVIN should be followed up with careful clinical
inspection +/-vulvoscopy.

Women with multi-focal HPV-related disease should be offered HIV testing.

Squamous cell carcinoma on a background of lichen sclerosus (LS)/lichen planus (LP)

Good control of lichen planus and lichen sclerosus with ultra-potent topical
steroids improves symptom and may reduce the incidence of developing SCC.

Often women are fearful of using ‘too much’ steroid cream and they
should be reassured that appropriate usage (less than 30 g tube of ultra-potent steroid ointment/cream,
such as Dermovate (clobetasol propionate 0.05%), over a 3-month period) is unlikely to be harmful and may be of benefit, both to scarring/vulval appearance as well as longer term risk of cancer.

women should be advised to avoid irritants that can exacerbate LS/LP, particularly
detergents, such as soap.

Women with uncomplicated lichen sclerosus or lichen planus can be followed
up in primary care and once quiescent and confident of self-management, 12-
monthly review is suggested.

Women with lichen sclerosus who develop new lesions should be referred to
secondary care, via a Cancer Wait Pathway, if these do not respond to nightly
ultra-high potency steroids within 1-2 weeks.

Mucosal malignant melanoma

Unlike cutaneous melanomas, vulval mucosal melanomas are not related to ultraviolet light exposure.
A small minority may be related to c-kit mutations, which are more common than in cutaneous
melanoma

Screening
There are currently no proven screening tests for vulval carcinoma.

Diagnosis of vulval cancer

Incisional biopsy (punch or wedge biopsy) ideally including the edge of a lesion, where there is a
transition from normal to abnormal tissues.

Biopsies should avoid a central ulcer, since this may not be diagnostic. Biopsies should be of adequate depth to allow differentiation between superficially invasive and those with invasion > 1 mm, since this will inform subsequent management.
Excision biopsy should be avoided, where possible, since this can limit options for more conservative treatment with wide local excision and sentinel node biopsy.

Women with suspicious vulval lesions should be referred to a rapid access
clinic for urgent assessment, as per NICE guidelines.

Women highly likely to have vulval cancer on clinical grounds should be
referred to a gynaecological cancer centre without waiting for biopsy results.

Clear documentation of clinical exam size of lesion, distance to the
midline/clitoris/anus/vagina/urethra and palpation of lymph nodes is
mandatory. Imaging, with indication of biopsy sites and/or clinical drawing is
essential for further treatment planning.

Suspicious vulval lesions should ideally be sampled with a punch or wedge
biopsy and excisional biopsy avoided until a diagnosis is made.

All cases vulval cancer should have diagnosis confirmed by a specialist multidisciplinary team (MDT) prior to planning radical treatme

Preoperative Investgations

All cases vulval cancer should have diagnosis confirmed by a specialist multi

disciplinary team (MDT) prior to planning radical treatment.

Gross nodal involvement should be excluded by clinical examination and
appropriate imaging / radiologic staging.

The groins can be assessed with ultrasound, but cross-sectional imaging (with computerised
tomography of chest, abdomen and pelvis (CT CAP), or magnetic resonance imaging (MRI)), will
provide additional information on the presence of pelvic lymphadenopathy and distant disease and should be employed prior to lymphadenectomy.

If radical surgery is proposed, there may be a role for positron emission tomography CT (PET-CT).

Vulval melanoma commonly presents with a more locally advanced lesion than cutaneous melanoma, since the area is difficult to visualise.

The risk of metastatic disease (both lymphatic and
haematogenous spread) is high.

Recommended imaging at diagnosis would include CT CAP and also CT or MRI head, since systemic disease and intra-cranial lesions are not uncommon.

Basal Cell Carcinoma
Distant disease spread is rare and no specific imaging is required, unless there is clinical suspicion of nodal disease.

HPV-associated squamous carcinomas have better outcomes than HPV-independent cancers.

Block positive p16 staining is a surrogate marker of HPV aetiology and is
recommended on all vulval squamous cell carcinomas.

Spread

The number of involved lymph nodes, the size of the largest metastatic deposit and the presence orabsence of extranodal spread should be recorded.

Sentinel lymph nodes (SLN)
A sentinel node can be defined as any lymph node receiving drainage directly from the primary tumour.

Staging

Management

Surgery with curative intent is the mainstay of treatment for all locally limited vulval carcinomas.

Joint pre-operative planning with gynaecological oncology and reconstructive
surgeons, including an examination under anaesthetic should be considered.

The aim of surgery for the primary tumour is removal of the cancer with clearance at all margins,
including the deep margin. Historically, a 1-2 cm macroscopic tumour-free margin was recommended on the basis of very limited retrospective data.

margins <8 mm were not associated with an increased risk.

Recommendation

Joint pre-operative planning with gynaecological oncology and reconstructive
surgeons, including an examination under anaesthetic should be considered.

1. Excision should be planned with macroscopic clearance of tumour by at least
   1 cm in situ with the goal of achieving clear margins on pathological
   assessment.

2. Closer margins may be considered to allow preservation of the
clitoris, urethra or anus. (Grade D)
3. As long as margins are microscopically clear of invasive disease, margins in
the fixed specimen of >2 mm are acceptable.

4. Data suggest that margins in the fixed specimen <2 mm are associated with higher rates of local recurrence.
5. Surgeons should be aware that specimens shrink when fixed, so wider
margins are required in situ to allow for this. (Grade D)
6. If VSCC extends to the pathological excision margins, re-excision is the
treatment of choice.( Grade D)
7. Some patients require access to reconstructive techniques at the time of vulval
surgery.(Grade D)

Radiotherapy

Surgery is commonly the treatment of choice for vulval cancer, but there may be indications for
radiotherapy, with or without concomitant chemotherapy, in both the primary and adjuvant setting.

Adjuvant (chemo)radiotherapy should ideally take place within 6 weeks of
surgery. (Grade B)

Postoperative radiotherapy is to be considered when:

• positive excision margins of the primary tumour, and further surgical excision
  not possible; Grade D
• pathological margins <2 mm, where repeat excision is not recommended,
  even though no consensus for the threshold of pathological margin distance
  exists. Each case should be individualised and discussed at MDT, taking into
  account patient factors (co-morbidities, previous treatment), location of close
  margins, and need for groin/pelvic radiotherapy; Grade D
• presence of >1 metastatic lymph node and/or the presence of extracapsular
  lymph node involvement. Grade B
  .

SLCOG

Adjuvant therapy in Vulval Cancer

1. Positive lymph nodes
2. Involved margins
3. Close margins <5mm

Adjuvant chemotherapy

• Definitive chemoradiation, generally weekly cisplatin with IMRT, is the
  treatment of choice in patients with locally unresectable disease. Grade B
  Locally advanced vulval cancer may respond to NACT and could be
  considered to downstage the local disease and avoid exenterative surgery. Grade C
• Consideration needs to be given to enrolling patients into clinical trials to explore primary chemoradiation (no surgery) alone for patients with earlier stages of locally advanced vulval cancer of HPV origin, to avoid exenterative surgery

Follow up

Treatment of recurrent disease

The management of recurrent disease is often challenging and requires a multidisciplinary team
approach.

Possible options include:

• Further surgery
• Radical radiation therapy with or without chemotherapy
• Neoadjuvant chemotherapy followed by tailored therapy
• Palliative radiotherapy
• Palliative chemotherapy
• Novel approaches including immunotherapy
• Best supportive care

Localised recurrence

imaging with MRI and/or CT (and PET CT when radical excision is a
consideration) is advised to exclude metastatic disease and determine extent of local disease.

surgery

Local recurrences should be treated as primary tumours with wide or radical local excision and
inguinofemoral lymphadenectomy in case of depth of invasion of more than 1 mm and not previously performed groin dissection or after previous SLN alone in accordance also with the recent ESGO guidelines.

Surgical re-excision of local and/ or groin relapse should be considered in
patients with relapsed disease amenable to surgery, in analogy with the
primary presentation of the disease. Grade D

Imaging by CT (or PET-CT when appropriate) of the thorax/abdomen/pelvis is
recommended prior to any treatment to tailor adequate approaches. Grade D

In patients not amenable to surgery, palliative chemotherapy, or radiotherapy,
or combination of both should be considered, depending on the previous
treatment modalities of the patient, her preferences and her fitness status.
Grade C
Systemic treatment may be considered in patients with distant metastases, but
published data are insufficient to recommend a preferred protocol.

Radiotherapy

External beam radiation utilising IMRT or VMAT is the standard approach. A dose to the primary site of 6,000 – 6,400 cGy is recommended.

Palliative radiotherapy may be used for relapsed disease when surgical options have been exhausted and the patient is not fit for high dose external beam radiotherapy.

Palliative chemotherapy

Palliative chemotherapy is to be considered in patients not fit for radiotherapy, or those who have no
options of more radiotherapy, nor further surgical excision or those who have distant metastatic disease.
Treatment is given with the intention of palliating symptoms to try and improve the quality of life.

The most commonly used cytotoxic drugs will include platinum agents, pyrimidines, taxanes and mitomycinc. Other drugs that may also be considered include gemcitabine and the vinca alkaloids.

Local nodal recurrence

radio-sensitizing chemotherapy to postoperative radiotherapy could be
considered.

Psychological/psychosexual support

Predictable short- and long-term effects from treatment include psychosocial concerns; lymphoedema;
altered sexual function and body image; and, following radiotherapy, possible altered bowel/bladder function.

holistic needs assessment (HNA) should be performed at pivotal points in
the cancer pathway.

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