DOI: 10.1111/tog.

12059

2013;15:22731

The Obstetrician & Gynaecologist

Review

http://onlinetog.org

Squamous vulval canceran update

Claire Bailey

1,
MRCOG, *

David Luesley

MA MD FRCOG

Specialist Trainee, City Hospital, Dudley Road, Birmingham, B18 7QH UK

Professor of Gynaecology Oncology, Pan-Birmingham Gynaecological Cancer Centre, City Hospital, Dudley Road, Birmingham, B18 7QH UK
*Correspondence: Claire Bailey. Email: cebailey@doctors.org.uk
2

Accepted on 15 June 2013

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

Please cite this paper as: Bailey C, Luesley D. Squamous vulval canceran update. The Obstetrician & Gynaecologist 2013;15:22731.

Introduction
Vulval cancer remains a relatively rare condition accounting
for 35% 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

2013 Royal College of Obstetricians and Gynaecologists

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 (Figure 2). Other
sites include the clitoris and perineum.

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Squamous vulval canceran update

Diagnosis is made by biopsy of a suspicious lesion. If the

lesion is small and well circumscribed it may be possible to
perform a wide local excisional biopsy. It is preferable to use
clinical photography to have a precise record of the site of the
lesion prior to performing the excision. A clearance margin
of at least 1 cm, including depth, is required. If there is no
wide margin of normal tissue then the lesion should be
biopsied rather than excised. Caution must be exercised when
performing excision biopsies. If further surgery is necessary,
wide local excision can be extremely challenging when the
initial lesion is no longer present.
For most lesions, it will be more appropriate to take one or
multiple biopsies. The procedure can be performed with local
anaesthetic using a Keyes biopsy blade (Figure 1). The site of
biopsy is crucial; it should be taken from the edge of lesion
and thus will include adjacent normal epithelium. Plain
lignocaine with or without adrenaline is first instilled with a
fine needle. A punch biopsy is then driven full thickness
through the epithelial surface. The surrounding skin is
pressed to release the desired tissue. A soluble suture is
usually required to achieve haemostasis.
Pathological examination will confirm histological type of
cancer and give details of depth of invasion and clearance
margins. Depth of invasion is defined as the measurement
from the epithelial junction of the most superficial adjacent
dermal papillae to the deepest point of invasion. It directly
correlates with lymph node involvement. Tumours with less
than 1 mm invasion have a negligible (less than 1%) risk of
lymph node metastasis thus the need for nodal resection is
eliminated in these cases. These tumours are termed
superficially invasive squamous carcinoma. All other
squamous vulval cancers have a risk of nodal spread that is
directly correlated to depth of invasion as shown in Table 1.
The exception to the rule is verrucous carcinoma, a subtype

of squamous carcinoma. These typically large condylomatous

lesions are well differentiated, low grade fungating tumours
and do not metastasise.

Staging
The natural history of vulval cancer is to grow by direct
extension followed by lymphatic embolisation. Initially this is
to local inguinal lymph nodes and later to femoral and the
external iliac chain. Final spread to distant sites is
haematogenous. Lymph node involvement can occur early
in the disease process. This is reflected by the International
Federation of Gynaecology and Obstetrics (FIGO) staging
system for vulval cancer (Table 2).5
Staging of disease prior to surgery is unsatisfactory as
palpation of groin nodes is notoriously difficult. More clinical
information may be obtained through the use of imaging
modalities and fine needle aspiration of enlarged nodes.

Figure 2. Squamous cell cancer of the vulva. A midline tumour with a

background of lichen sclerosis

Table 1. Depth of stromal invasion versus nodal status in 578 patients

with squamous cell carcinoma of the vulva
Depth of Invasion (mm)
<1
1.12
2.13
3.15
>5

Figure 1. Keyes punch biopsy blade 4 mm

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% with nodal involvement

0
7.6
8.4
26.7
34.2

Adapted from Hacker NF, van der Valden J. Conservative

management of early vulvar cancer. Cancer 1993;71:16737.
Copyright 1993 American Cancer Society

2013 Royal College of Obstetricians and Gynaecologists

Bailey and Luesley

Table 2. Staging of cancer of the vulva (adapted from FIGO Committee of Gynaecology Oncology), 2009.
Stage I

Tumour conned to the vulva.

IA
IB
Stage II
Stage III
IIIA

Lesions 2 cm in size, conned to the vulva or perineum and with stromal invasion 1.0 mm, no nodal metastasis.
Lesions >2 cm in size or with stromal invasion >1.0 mm, conned to the vulva or perineum, with negative nodes.
Tumour of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes.
Tumour of any size, with or without extension to adjacent perineal structures, with positive inguino-femoral lymph nodes.
(i) With 1 lymph node metastasis (5 mm), or
(ii) 12 lymph node metastases (<5 mm).
(i) With 2 or more lymph node metastases (5 mm), or
(ii) 3 or more lymph node metastases (<5 mm).
Positive nodes with extracapsular spread.
Tumour invading other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures.
Tumour invades any of the following:
(i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or xed to pelvic bone, or
(ii) xed or ulcerated inguino-femoral lymph nodes.
Any distant metastasis including pelvic lymph nodes.

IIIB
IIIC
Stage IV
IVA

IVB

Mortality is directly related to stage of disease at

presentation. Data from the National Cancer Institute
shows a 5 year survival rate of 86% for stage I compared to
53% for stage III and 15% for those with distant metastases.6

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.7

Treatment of early vulval cancer

The current trend of management of early vulval cancer
(stage II or less) is to leave as much vulval tissue as possible.
There are no randomised controlled trials to support this
practice but a review of the data found no difference in
local recurrence rates between radical wide local excision
and radical vulvectomy. If the primary lesion is a
superficially invasive squamous cell carcinoma then

2013 Royal College of Obstetricians and Gynaecologists

resection of lymph nodes is not necessary. For all

other tumours management includes inguinofemoral
lymphadenectomy. Lateral tumours, defined by their
location of more than 1 cm from the midline, drain to
the ipsilateral lymph nodes. For these tumours, performing
an ipsilateral lymph node resection has the same outcome
with regard to groin recurrence as a bilateral resection.8 If
the lesion is central then both groins should be resected.
Superficial lymph node resection results in a higher
incidence of recurrence so both superficial inguinal and
deep femoral lymph nodes should be resected. En bloc groin
resection has been replaced with dissection through a
separate incision.
Surgery related morbidity is a substantial problem and is
mainly related to groin resection. An analysis of 164 patients
that underwent inguinofemoral lymphadenectomy revealed
that older age, diabetes, en bloc surgery and higher drain
production on the last day of drain in situ gave a higher risk of
developing short-term complications (wound breakdown,
infection and lymphocele). Younger age and lymphocele gave
an increased risk of suffering long-term sequelae
(lymphoedema and cellulitis).9 One small randomised
controlled trial compared lymph node resection with
primary radiotherapy for patients with early vulval cancer.
Morbidity from lymphoedema and life threatening
cardiovascular complications was reduced in the
radiotherapy group but groin recurrence rate increased
(relative risk 10.21).10 Radiotherapy should, therefore, only
be considered as first-line for early disease when a patient is not
fit enough to withstand a surgical procedure.
Radiotherapy may be required as an adjuvant for early
disease, for example in cases where margins are inadequate
(less than 8 mm) or if multiple lymph nodes display
microscopic involvement.

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Squamous vulval canceran update

Treatment of advanced vulval cancer

For stage III and IV disease a combination of treatment
modalities can be used according to the individual case.
Surgery entails radical vulvectomy with en bloc resection of
bilateral inguinofemoral lymph nodes. Most patients require
post operative radiotherapy to the pelvis and groin. Pre
operative neoadjuvant radiotherapy or chemoradiation can
be used to improve operability and reduce extent of surgery
required including those cases that would otherwise require a
stoma. There are several small case series published that
support the use of chemoradiation in cases of advanced
disease that would otherwise warrant pelvic exenteration. The
regime was found to have acceptable morbidity even in the
elderly and in those achieving a complete response, the need
for surgery was avoided.11 Overall, there does not appear to
be a significant difference in survival or treatment-related
adverse effects when chemoradiation is compared with
primary surgery in cases of advanced disease.12 Data
assessing quality of life issues with the different treatments
is lacking.

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%.13
The long-term outcome following sentinel lymph node
biopsy has been evaluated in the Netherlands. Of 403 women
undergoing surgical excision for early stage vulvar cancer, 276
had no sign of metastases in sentinel nodes and so did not
have further lymphadenectomy. The women were followed
for an average of 35 months after surgery. Women

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undergoing sentinel node biopsy suffered fewer short- and

long-term complications compared to their lymph node
resection counterparts. The rate of cancer recurrence in the
groin was 3% which was deemed comparable to women
treated with lymphadenectomy.14 Performing sentinel lymph
node biopsy requires extensive clinical experience and it is
not yet implemented into the routine treatment for early
vulval cancer. The Groningen International Study on Sentinel
Nodes in Vulvar Cancer (GROINSS-V) II is an observational
multicentre trial currently recruiting patients to further
evaluate the role of sentinel node biopsy.15

Recurrence of disease
A large, multicentre trial of 502 patients with primary vulval
carcinoma demonstrated a recurrence rate of 37%. More than
half of the recurrences occurred at the perineum. Three
statistically significant risk factors were identified; FIGO stage
greater than II (P = 0.029), positive lymph nodes (P = 0.009)
and vascular space invasion (P = 0.004). Site of recurrence
correlated to survival with a 5 year survival rate of 60% for
perineal recurrence, 27% for inguinal and pelvic recurrence
and 15% for distant recurrences.16 Radical re-excision or
radiation can be employed to manage local relapse.

Psychosexual issues following vulval cancer

It is essential to address the sexual impact that genital surgery
can have. The issue should be raised pre operatively and
ideally included in the consent process. Scarring and loss of
genital architecture can cause narrowing of the introitus and,
in turn, lead to dyspareunia. It can also leave a woman feeling
defeminised. Arousal and sexual pleasure can be diminished
and it may not be possible to achieve an orgasm. It is common
for women to feel numbness in the genital area following
vulvectomy although this may improve with time. An analysis
of sexual function in 42 patients after radical wide local
excision or vulvectomy demonstrated disruption to sexual
excitement and orgasm but interestingly sexual desire was not
diminished. More women became sexually inactive with time
and there was a reluctance to initiate relationships with new
sexual partners due to the genital changes. Sexual outcome
correlated with degree of surgical intervention with more
conservative excision better preserving sexual function.17
A Cochrane review examined five interventions for
psychosexual dysfunction in 413 women treated for
gynaecological cancer. No benefit was found with clinical
nurse specialist input, psychoeducational group therapy or
couple coping intervention. Vaginal estrogen after
radiotherapy was suggested to have short-term benefit but
more robust studies are required in this area.18 A
psychosexual counsellor and reconstructive plastic surgeon
have an important role is managing sexual issues and should

2013 Royal College of Obstetricians and Gynaecologists

Bailey and Luesley

be part of the multidisciplinary team caring for women with

vulvar cancer.

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.
There can be a role for reconstructive surgery at a later
stage. Cosmetic appearance of the vulva can be enhanced by
procedures such as labial reconstruction.

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.

Disclosure of interests
None declared.

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