Key content
 Squamous vulval cancer is a rare condition with a poorly
understood aetiology. Two factors seem to have an important role;
infection with human papilloma virus leading to vulva
intraepithelial neoplasia and chronic inflammatory vulval
dermatoses such as lichen sclerosus.
 Diagnosis based on biopsy and management is complex.
Consideration is given to site and size of lesion as well as the FIGO
staging system.
 Depending on the stage of cancer, other treatment modalities such as
chemoradiation may play a role in the management of the condition.
Learning objectives
 To know how to perform an incisional biopsy of a suspicious
vulval lesion.
 To acknowledge that incisional biopsy is the preferred mode of
diagnosis for vulval cancer and appreciate that the role of wide
local excision is limited.
 To be aware of the use of sentinel node biopsy in the management
of vulval cancer.
 To understand that reconstructive surgery has an important place
in the management of these patients.
Ethical issue
 How can health professionals help women cope with the
psychosexual sequelae after vulval surgery?
Keywords: sentinel node biopsy / vulval intraepithelial neoplasia /vulval cancer

Introduction
Vulval cancer remains a relatively rare condition accounting
for 3–5% of female genital cancers and historically affecting
older women. Approximately 90% of tumours are squamous
in origin. Evidence suggests that there are two separate
aetiological factors leading to vulval cancer. First, tumours
developing from vulval intraepithelial neoplasia (VIN)
caused by human papilloma virus (HPV) infection.
Secondly, the development of squamous cell hyperplasia
and atypia from chronic inflammation and itch in
non-neoplastic vulval dermatoses such as lichen sclerosus.
This leads to HPV-negative VIN and eventually to invasive
keratinising squamous cell carcinoma.
Recently, the prevalence of HPV associated VIN has
significantly increased and consequently, the incidence of
vulval cancer in young women is rising. One study
demonstrated more than a 10-fold increased incidence of
cases in women younger than 50 years of age over a 20-year
period.1 Rates of progression to invasive cancer are imprecise
but in one systematic review of 88 patients with untreated
VIN 3, eight (9%), progressed to cancer during the 8 years of
observation.2 HPV serotypes 16 and 18 are strongly
associated with VIN. A study demonstrated a 5.3-fold
increase in vulval neoplasia in subjects positive for HPV-16
antibodies and in those with high antibody levels this rose to
a 20-fold increase.3 The vast majority of these carcinomas
harbour warty or basaloid VIN and they share many common
risk factors with cervical cancer including multiplicity of
sexual partners, early age at initiation of sexual intercourse,
cigarette smoking and low socio-economic status.4 It is,
therefore, likely that the HPV vaccination programme to
reduce cervical cancer will also provide protection against
HPV-related vulval squamous cancer.

Presentation and diagnosis
Women with vulval cancer are rarely asymptomatic. The
most common symptoms include pruritis, burning, soreness,
bleeding, pain or a lump. Any woman presenting with such
symptoms should be examined. Genital warts are not
common in postmenopausal women and so this finding
should raise the suspicion of cancer. Other concerning
features are ulcers, a fungating mass, irregularity of skin
contour, depigmentation or hyperpigmentation and groin
lymphadenopathy. Most squamous cell carcinomas are
unifocal and occur on the labia majora. Other
sites include the clitoris and perineum.

Depth of stromal invasion versus nodal status in 578 patients
with squamous cell carcinoma of the vulva
Depth of Invasion (mm) % with nodal involvement
<1 0
1.1–2 7.6
2.1–3 8.4
3.1–5 26.7
>5 34.2

Staging of cancer of the vulva (adapted from FIGO Committee of Gynaecology Oncology), 2009.
Stage I Tumour confined to the vulva.
IA Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1.0 mm, no nodal metastasis.
IB Lesions >2 cm in size or with stromal invasion >1.0 mm, confined to the vulva or perineum, with negative nodes.
Stage II Tumour of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes.
Stage III Tumour of any size, with or without extension to adjacent perineal structures, with positive inguino-femoral lymph nodes.
IIIA (i) With 1 lymph node metastasis (≥5 mm), or
(ii) 1–2 lymph node metastases (<5 mm).
IIIB (i) With 2 or more lymph node metastases (≥5 mm), or
(ii) 3 or more lymph node metastases (<5 mm).
IIIC Positive nodes with extracapsular spread.
Stage IV Tumour invading other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures.
IVA Tumour invades any of the following:
(i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone, or
(ii) fixed or ulcerated inguino-femoral lymph nodes.
IVB Any distant metastasis including pelvic lymph nodes.

Treatment
Vulval cancer should be managed by a multidisciplinary team
in a cancer centre.
Surgery remains the gold standard of treatment for vulval
cancer. Previously, women routinely underwent extensive
and mutilating surgery in the form of radical vulvectomy
with en bloc bilateral groin node resection. Although
survival rates are impressive after a radical procedure,
complication rates are high. As many patients are frail and
elderly with significant co-morbidities they may be deemed
unsuitable for extensive surgery. Treatment should be
tailored to the individual and should take into
consideration her age, fitness, sexual function, tumour
size, tumour site and stage of disease. Although most
commonly performed under general anaesthesia it should
be remembered that for those women deemed unfavourable
for this mode of anaesthetic, a combination of regional
anaesthetic with conscious sedation has been shown to be
an effective and safe alternative.

A role for sentinel lymph node biopsy
The sentinel lymph node is the node to which the tumour
first drains. For women with early disease, only 20% will have
lymph node metastases. The majority of these patients are,
therefore, undergoing an unnecessary lymph node resection
and the associated complications. If the sentinel lymph node
is isolated and resected, it can be examined by frozen section
pathology. A sulphur colloid tagged with the radioactive
technetium-99 m is injected near the tumour. By using
scintigraphic imaging, the node or nodes that take up the
radioactive substance can be identified. Similarly, blue dye
can be injected intraoperatively about 15 minutes before
biopsy. Visual inspection can then identify the sentinel node.
A frozen section procedure takes less than 20 minutes
enabling rapid microscopic analysis of the node. If there is
no evidence of metastases then further resection can be
avoided. One small study of 59 patients undergoing
inguinofemoral lymphadenectomy evaluated the accuracy of
the technique. Intraoperative sentinel node biopsy was
performed in all cases prior to lymph node resection.
Routine histopathological examination revealed 27 cases of
lymph node metastases, all of which were identified at the
time of sentinel lymph node biopsy. The negative predictive
value for a negative sentinel lymph node was 100%.

Reconstructive surgery
Reconstructive surgery plays an important role in the
cosmetic and functional results of wide radical vulval
surgery. Gynaecological oncologists will have experience in
such surgery but input from a plastic reconstructive surgeon is
often necessary. Surgical techniques range from simple
procedures for introital stenosis to complicated procedures
where large areas of skin and underlying tissue are used as
flaps to cover defects caused by radical surgery. It is preferable
to perform reconstruction at the same time as primary
surgery. A variety of graft procedures, realignment of standard
incisions and use of vascular pedicle flaps can be employed. A
study of more than 60 women requiring reconstructive plastic
surgery involving use of fasciocutaneous or and
myocutaneous skin flaps for defects led to excellent wound
healing and cosmetic results.19 Reconstruction can allow for
more radical excisions and thus the achievement of sufficient
clearance margins can be improved.

Conclusion
Vulval cancer is rare and so should be managed in specialist
cancer centres with a multidisciplinary approach. The
principle of management is to eradicate disease whilst
preserving as much function as possible. Morbidity may be
reduced by the use of sentinel node biopsy although this
treatment should be undertaken in the context of a clinical
trial until further research data are available. Sexual
dysfunction is an important and distressing consequence of
vulvar surgery that needs to be recognised by health
professionals and addressed with patients before surgery.