REVIEW

Invasive cervical cancer Cervical cancer is more common than other HPV derived
cancers (vagina, vulva, penile, anal, and laryngeal) due to the
transformation zone of the cervix. The transformation zone is the
Ioannis C Kotsopoulos area of the cervix where columnar cells exposed to the external
Clare L Newton surface of the cervix undergo the process of squamous meta-
plasia, and transform into squamous cells. This area is particu-
Timothy A Mould larly susceptible to the effects of oncogenic HPV.

Abstract
In this review, the aetiology of cervical cancer is discussed plus HPV Vaccination
vaccination, diagnosis, imaging techniques, the new FIGO staging Most people who come into contact with HPV can clear the virus
and management with surgical options for stage 1a1-1b2 and non- from their bodies. In some women the HPV persists and can
surgical options for stage 1b3-3b cervical cancer. Palliative treatments cause abnormal cells to develop in the cervix, vulva, vagina and
and exenterative surgery are included. anus. It is estimated that vaccinating girls against HPV could save
Keywords cervix cancer; chemoradiation; cone biopsy; radical up to 400 lives per year in the UK.
hysterectomy; trachelectomy There are currently three vaccines available:

Cervarix a bivalent vaccine active against HPV 16 and 18.

Gardasil, quadrivalent vaccine active against HPV 6, 11
Introduction plus 16 and 18.

Gardasil 9, nonavalent vaccine against 6, 11 plus 16, 18,
Cervical cancer is the second most common cancer in women
31, 33, 45, 52 and 58
worldwide, but relatively rare in developed countries due to
Initially Cervarix was used in the UK vaccination program.
screening programmes. In the UK, approximately 3100 women
This was switched to Gardasil quadrivalent vaccine due to the
are diagnosed with and 900 women die from cervical cancer each
reduction in genital warts demonstrated in the Australian HPV
year, with screening estimated to save up to 5000 lives per year.
vaccine program. The reduction in wart treatments produced a
It is the most common cancer in women under 35 years old due
significant cost saving. Girls aged between 12 and 13 are given
to its aetiology of human papillomavirus.
the Gardasil via the school vaccination program. It is given as a
series of two injections 6e12 months apart. The vaccine is pre-
ventative rather than therapeutic and is timed to be given before
Aetiology the onset of sexually activity and thus prior to exposure of HPV.
Girls can have the HPV vaccine up to aged 18 on the NHS, but if
The cause of cervical cancer is persistent human papillomavirus they are aged 14 or over they need a series of three injections
(HPV) infection. HPV is detected in 99 % of cervical tumours, in rather than two because the immune response to the vaccina-
particular the oncogenic subtypes such as HPV 16 and 18 which tions are not as good in older girls. The current evidence suggests
account for 70% of all cervical tumours. Other oncogenic sub- that the vaccines offer a protection for at least 10 years.
types of HPV are 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, In Australia where the quadrivalent vaccine has been used
73, 82. since 2007 there has been a 90% reduction in genital warts in
Newly acquired genital HPV infections are usually eliminated heterosexual men and women under the age of 21 years.
by the immune system. If this does not occur, the longer an HPV vaccination results in 89% reduction in CIN grade 3 or
oncogenic HPV subtype is present and the greater the amount of worse, an 88% reduction in CIN grade 2 or worse, and a 79%
the virus on the cervix, the higher the chance of developing a reduction in CIN grade 1. Younger age at vaccination is associ-
precancerous lesion of the cervix. A precancerous lesion can ated with increasing vaccine effectiveness (86% for CIN grade 3
progress to invasive cancer, but may also regress if the HPV is or worse for women vaccinated at age 12e13 compared with
eliminated. Human immunodeficiency virus (HIV) infection and 51% for women vaccinated at age 17). It is expected that
other immune deficiency states such as transplant rejection, drug vaccination will reduce the incidence cervical cancer by 70%.
usage and smoking all act as cofactors to prevent successful Women are still advised to attend for cervical screening from
elimination of HPV by the immune system. the age of 25 even if they have been vaccinated. Cervical
screening is changing to HPV as the primary test from the end of
2019 in the UK. Four randomized studies have shown an
Ioannis C Kotsopoulos MD MPhil PhD, Subspecialty Trainee in increased effectiveness of screening using primary HPV testing
Gynaecological Oncology, University College London Hospitals, compared to the traditional Pap smear.
London, UK. Conflicts of interest: none declared. HPV vaccination of boys has been approved by the UK gov-
Clare L Newton MBBS BSc MRCOG MD, Consultant Gynaecological ernment but has not yet been started.
Oncologist, University Hospital Bristol, Bristol, UK. Conflicts of
interest: none declared.

Timothy A Mould MBBS MA DM FRCOG, Consultant Gynaecological Diagnosis of cervical cancer

Oncologist, University College London Hospitals, London, UK.
Conflicts of interest: none declared. Diagnosis is made by history, examination and biopsy.

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 REVIEW

History A suspicious cervix, or a woman with persistent symptoms is

The symptoms associated with cervical cancer are very common referred to colposcopy for a more detailed examination and bi-
and non-specific (see list below), and a high index of suspicion opsies. Figure 1 shows an image of cervical cancer.
may be needed. The same symptoms are seen with Chlamydia
trachomatis infection. It is important to test for chlamydia in Investigations
young women with these symptoms as the prevalence is high. Pathology: the diagnosis of cervical cancer is confirmed by bi-
Symptoms and signs suggestive of cervical cancer are: opsy and pathological assessment. The common types of cervical

Postcoital bleeding e the most common symptom cancer are:

Intermenstrual bleeding
Squamous cell carcinoma (approximately 80%)

Postmenopausal bleeding
Adenocarcinoma (approximately 15%)

Vaginal discharge (blood stained), often malodorous Rarer cell types include small cell and large cell neuroendo-

Pelvic pain crine tumours, sarcoma, lymphoma and melanoma.

Suspicious cervix on examination Squamous cell carcinomas arise from the precursor cervical
In later stages of cervical cancer: intraepithelial neoplasia (CIN) in squamous cells. Adenocarci-

Loin pain from hydronephrosis due to obstruction of the nomas arise from the precursor cervical glandular intraepithelial
ureters from lateral spread neoplasia (CGIN) in glandular mucus producing cells.

Sciatica as the cancer compresses sciatic nerve roots Local spread of cervical cancer is usually to the vagina and

Swollen leg from deep vein thrombosis due to compression laterally to parametrium (the connective tissues to the side of the
of iliac veins cervix), then the pelvic side wall which causes ureteric
The prevalence of post-coital bleeding in the community is obstruction and hydronephrosis. Anterior and posterior spread to
thought to be between 0.7 and 9%. Post-coital bleeding is known bladder and bowel can occur but this is usually later with larger
to be a warning sign for cervical cancer and is the presenting tumours. Lymphatic spread occurs to pelvic lymph nodes and
symptom in 6%e10% of such patients. The NHS Cervical then to the para aortic nodes. Spread via the blood to the lungs
Screening Programme suggests referral to a gynaecologist if a and liver occurs late.
woman presents with post-coital bleeding and is over 40 years There are risk factors that determines if the patient is high risk
old, or if their cervix looks abnormal. NHS suspected cancer or low risk for metastatic disease and they are:
guidelines suggest that post-coital bleeding for more than 4
Tumour grade (graded 1 to 3)
weeks in women greater than 35 years old should be referred
Tumour size
urgently to be seen within 2 weeks, and for all other cases of
Depth of stromal invasion into the cervix
repeated unexplained PCB, referral should be early, within 4e6
The presence of lymphovascular space invasion (LVSI)
weeks.
Status of lymph nodes
Post-menopausal bleeding can herald an endometrial cancer Imaging: all patients with a diagnosis of cervical cancer >
and therefore these women may need an ultrasound to measure stage 1a1 have an MRI of the pelvis (Figure 2) to define local
the endometrial thickness and an endometrial biopsy if the spread, and also a CT of the abdomen and chest to check for any
endometrial thickness is 4 mm. distant spread. MRI is used to evaluate the cervix as it is able to
detect spread to the parametria. CT is not able to demonstrate
Examination this confidently. MRI is more accurate than clinical staging at
Examination of the cervix with a speculum is mandatory. examination under anaesthesia.
Criteria for lymph-node involvement on CT and MRI are based
on size and morphology. A node is judged suspicious when
shape is spherical and the shortest diameter is greater than 10
mm. More recently, positron emission tomography (PET/CT) has
been seen to have the potential to accurately delineate the extent
of disease and the disease in distant sites, with high sensitivity
and specificity. PET/CT is especially useful in detecting lymph
node involvement and is more sensitive than CT alone or MRI
especially in detecting paraaortic lymph node involvement. PET/
CT may be the imaging modality of choice for distant spread if it
is available.
Diffusion-weighted imaging (DWI) is a form of MR based
imaging that assesses the water diffusion properties of tissue.
Generally, densely cellular tissues or those with cellular swelling
exhibit lower diffusion coefficients and this difference has helped
to differentiate between normal tissue and cancer. This can be
helpful to determine if lymph nodes are involved with disease, or
Figure 1 Cervical cancer.
if there is residual tumour or recurrence following treatment.

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 REVIEW

the likely involvement of lymph nodes. Both of these are

Practice points important because the treatment modality changes from sur-
gery to chemoradiotherapy if parametrial or nodal involvement
C Anyone with irregular vaginal bleeding should have a speculum is present.
examination to examine the cervix The TNM (tumour, nodes, metastasis) system can also be
C Young women with irregular vaginal bleeding should be tested for used to stage cervical cancer.
Chlamydia trachomatis Examination under anaesthesia is still helpful in women with
C Women with postmenopausal bleeding should have an ultrasound larger tumours for the purposes of treatment planning.
scan to measure endometrial thickness and have a biopsy if the
endometrial thickness is  4 mm
Management
Every patient with a diagnosis of cervical cancer should be dis-
Staging (Table 1) cussed at the multidisciplinary team meeting (MDM) prior to
starting treatment, as this plays a crucial role in the management
Two FIGO staging systems are currently used for staging cervical
of women with cervical cancer.
cancer, 2009 and 2018. There is currently a transition to the 2018
Core members of the multi-disciplinary team:
system.

Gynaecological Oncologist (surgeon)
The 2009 system was a clinical staging system, and did not

Clinical Oncologist (radiation  chemotherapy)
include information obtained from imaging. This was devised

Medical Oncologist (chemotherapy)
because most cases of cervical cancer occur in developing

Pathologist
countries with poor resources, and the clinical staging system

Radiologist
enabled comparisons of data between different countries. Lymph

Clinical nurse specialist
node status did not alter FIGO staging, as nodal spread was not
Management depends on the stage of the tumour, and can be
confirmed if treatment was with chemo radiation.
influenced by the fertility wishes of the patient. Principles of
In 2018, FIGO introduced a new staging system for Cervical
treatment are:
Cancer (Table 1). This includes information obtained using
- Combined treatment of radical surgery followed by post-
pre-treatment imaging, and on lymph node status. The main
operative chemoradiation increases morbidity than either
differences in the new system are that stage 1B has now three
treatment alone but survival is not increased.
sub-stages based on maximum tumour size (<2 cm, 2e4 cm
- If parametrial spread, or lymph node spread is suspected on
and >4 cm) and that lymph nodes status is also included (stage
pre-treatment imaging and assessment, chemoradiation is
IIIc). MRI, CT and CT PET scanning can be used for staging
chosen as the primary treatment, and surgery not
which means that the information obtained from examination
undertaken.
under anaesthesia is used less often. MRI is more accurate than
Patients should be considered for any available clinical trials,
clinical assessment in defining the presence and extent of
and these should be highlighted at the time of MDM discussion.
parametrial involvement, and imaging is also able to determine

Figure 2 MRI of the cervix.

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 REVIEW

From Bhatla N, et al. Revised FIGO staging for carcinoma of the cervix uteri. Int J
New FIGO staging system of cervical cancer Gynaecol Obstet. 2019; 145(1): 129e135, with kind permission from Wiley-
Blackwell.
Stage Description
When in doubt, the lower staging should be assigned.
a
Imaging and pathology can be used, where available, to supplement clinical
I The carcinoma is strictly confined to the cervix findings with respect to tumor size and extent in all stages.
b
(extension to the uterine corpus should be The involvement of vascular/lymphatic spaces does not change the staging.
disregarded) The lateral extent of the lesion is no longer considered.
c
Adding notation of r (imaging) and p (pathology) to indicate the findings
IA Invasive carcinoma that can be diagnosed only that are used to allocate the case to Stage IIIC Example: If imaging indicates
by microscopy, with maximum depth of pelvic lymph node metastasis, the stage allocation would be Stage IllClr. and
invasion <5 mma if confirmed by pathologic findings, it would be Stage IIIClp. The type of im-
aging modafity or pathology technique used should always be documented.
IA1 Measured stromal invasion <3 mm in depth
IA2 Measured stromal invasion 3 mm and <5
Table 1
mm in depth
IB Invasive carcinoma with measured deepest
invasion 5 mm (greater than Stage IA).
lesion limited to the cervix uterib
Practice points
IB1 Invasive carcinoma 5 mm depth of stromal
invasion, and <2 cm in greatest dimension C The most common types of cervical cancer are squamous cell
IB2 Invasive carcinoma 2 cm and <4 cm in
carcinoma and adenocarcinomas.
greatest dimension C A new FIGO staging system was introduced in 2018.
IB3 Invasive carcinoma 4 cm in greatest C All patients with a diagnosis of cervical cancer > stage 1a1 have
dimension
an MRI cervix to define local spread and a CT CAP for lymph node
II The carcinoma invades beyond the uterus, but
status and to determine if there is any distant spread
has not extended onto the lower third of the C All women with cervical cancer and a lesion > stage 1a2 had an
vagina or to the pelvic wall
examination under anaesthetic for clinical staging in the past, but
IIA Involvement limited to the upper two-thirds of
MRI is more accurate for determination of parametrial involve-
the vagina without parametrial involvement
ment meaning that EUA is used less often.
IIA1 Invasive carcinoma <4 cm in greatest C All women with a diagnosis of cervical cancer should be discussed
dimension
at a multi-disciplinary team meeting (MDM)
IIA2 Invasive carcinoma 4 cm in greatest C Combined treatment of radical surgery followed by post-operative
dimension
radiotherapy increases morbidity than either treatment alone but
IIB With parametrial involvement but not up to
survival is not increased
the pelvic wall
III The carcinoma involves the lower third of the
vagina and/or extends to the pelvic wall and/ Treatment by stage (FIGO 2018)
or causes hydronephrosis or nonfunctioning Stage 1a1 e treatment can be conservative with a cone biopsy, or
kidney and/or involves pelvic and/or para- LLETZ. It is essential that all margins are clear of pre-invasive
aortic lymph nodesc disease. Alternatively a simple hysterectomy may be offered for
IIIA The carcinoma involves the lower third of the women who have completed their family. The risk of lymph node
vagina, with no extension to the pelvic wall involvement is only 0.4% and therefore lymphadenectomy is
1IIB Extension to the pelvic wall and/or unnecessary.
hydronephrosis or nonfunctioning kidney Stage 1a2 e cone biopsy, or simple extra fascial hysterectomy
(unless known to be due to another cause) if completed their family, and a pelvic node dissection. The risk
IIIC Involvement of pelvic and/or para-aortic lymph of lymph node involvement is 5% and therefore bilateral pelvic
nodes, irrespective of tumor size and extent lymphadenectomy to assess for spread to the lymph nodes is also
(with r and p notations)c recommended. The chance of parametrial involvement in this
IIIC1 Pelvic lymph node metastasis only group is only 0.6%, and therefore radical resection of the para-
IIIC2 Para-aortic lymph node metastasis metria is not needed. If fertility is desired then a cone biopsy or a
IV The carcinoma has extended beyond the true simple trachelectomy can be performed. If the surgical resection
pelvis or has involved (biopsy proven) the margins are clear and the lymph nodes do not have metastatic
mucosa of the bladder or rectum. (A bullous disease, no further treatment is required. If there are positive
edema, as such, does not permit a case to be margins or lymph node involvement, external beam radiotherapy
allotted to Stage IV) is given.
IVA Spread to adjacent pelvic organs Stage 1b1 e
IVB Spread to distant organs Tumours less than 1 cm diameter, are only just bigger than
1a2 can be treated in a similar way.

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Tumours between 1 cm and 2 cm - radical hysterectomy, or Surgical treatments

radical trachelectomy (resection of the cervix but preserving The ovaries can be conserved in squamous cell carcinomas as the
the body of the uterus), plus bilateral pelvic lymphadenec- cancer is not hormone dependent. Adenocarcinomas of the cer-
tomy. Radical refers to resection of the parametrial tissue vix are not thought to be hormone dependent, but consideration
around the cervix and vagina. is taken to remove the ovaries nevertheless. It is possible for
Stage 1B2 e radical hysterectomy and bilateral pelvic lym- larger adenocarcinomas of the cervix to metastasize to the
phadenectomy. A trachelectomy is not usually advised when the ovaries. The decision to remove or preserve the ovaries is highly
tumour is greater than 2 cm diameter as the recurrence rates are individualized and should be discussed and agreed prior to
higher. surgery.
Stage 1B3 e chemo radiation e see below. Cone biopsy: a cone biopsy can be performed by cold knife,
Stage 2a 1 e radical hysterectomy and bilateral pelvic lym- laser, or electocautery needle under local anaesthesia or general
phadenectomy. A trachelectomy is not usually advised when the anaesthetic as a day case. The difference between a cone biopsy
tumour is greater than 2 cm diameter as the recurrence rates are and a LLETZ/LEEP is the depth of excision. LLETZ has a depth
higher. up to 1 cm. A cone biopsy can be as deep as 2.5 cm.
Adjuvant treatment after surgery: Complications include primary haemorrhage or more
Postoperative pathology is reviewed at the MDT. commonly secondary haemorrhage characteristically at 10e14
Women are advised to have adjuvant chemoradiotherapy days which occurs as a significant bleed in 3%. In subsequent
following surgery if they have any of the following findings: pregnancies, the rates of pre-term delivery increase from a
Positive pelvic lymph nodes background of 1.5% to around 4% following a cone biopsy and
Positive surgical margins is directly related to the depth of the cone biopsy.
Women treated with surgery with clear margins and clear Radical trachelectomy: a radical trachelectomy is an option for
nodes but with the pathology showing tumour >4 cm, deep in- highly selected patients with small tumours who wish to pre-
vasion into the cervix more than 50% and lymphovascular space serve their fertility. This can be approached vaginally, or
invasion (LVSI), have worse progression free and overall sur- abdominally via a laparoscopic/robotic or open approach. The
vival. These women will be considered for adjuvant chemo cervix, parametrium and cuff of vagina are removed. After the
radiation. specimen has been removed a permanent cervical cerclage suture
Stage 1b3, Stage 2a2 e stage 3b e the standard recommended is placed at the uterine isthmus (where the uterus joins the
management of stage Ib3, 2a2 and above is radical chemo- endocervix) to help support a pregnancy to be carried to full
radiotherapy (see non-surgical management in the next section). term. The vagina is then sutured to the uterine isthmus trying to
Stage 4 e treatment is individualized according to the pattern avoid uterine isthmic stenosis and a resulting haematometra.
of spread. Complications include primary haemorrhage, ureteric,
Spread to bladder or rectum may be managed with a bladder and bowel damage.
defunctioning stoma and radical chemoradiation if the patient is Although greater than 70% of pregnancies are carried to 37
fit, or palliative radiation to the pelvis if not. weeks or above, late miscarriage and pre-term labour rates are
In rare cases, the disease has extended to bladder or rectum significantly increased (16% vs 12% in the general population).
without reaching the pelvic side wall, and without distant spread. First trimester miscarriage rates are not increased. Delivery needs
Radical surgery to remove the cancer with likely adjuvant che- to be by caesarean section due to the cervical suture, which re-
moradiotherapy can be considered (see exenterative surgery mains in situ. This is a standard lower segment caesarean.
below), although this is not standard treatment). The rates of cancer recurrence following a trachelectomy are
If distant spread has occurred, primary chemotherapy would comparable to radical hysterectomy providing the cervical cancer
be recommended followed by palliative radiation to the pelvis. If measures 2 cm and there is no lymphovascular space invasion.
the response to primary chemotherapy is good, chemo- Radical hysterectomy: a radical hysterectomy can be
radiotherapy to the pelvis may be considered. approached abdominally via open, laparoscopic or robotic sur-
gery. The vaginal version (Schauta’s) is used rarely as the par-
ametrial resection is less extensive.
Data from the recent LACC trial (see further) demonstrated
better survival rates and lower recurrences with open surgery
Practice points compared to minimal access surgery (laparoscopic or robotic) for
visible tumours. Patients should be informed of the current data
Treatment depends on stage: comparing routes of surgery and offered the open approach, if in
agreement.
C Stage 1a1-cone biopsy, LLETZ or simple hysterectomy A radical hysterectomy includes removal of the uterus, tubes,
C Stage 1a2 e simple hysterectomy/cone biopsy/simple trache- cervix, parametrium and cuff of vagina. Different levels of radi-
lectomy þ pelvic lymhadenectomy cality describe the amount of parametrium removed which is in
C Stage 1b1/2 and 2a1 e Radical hysterectomy or radical trache- turn determined by the size of the tumour.
lectomy þ pelvic lymphadenectomy
C Stage 1b3, 2a2 - 3b e Radical chemoradiotherapy Complications include primary haemorrhage, ureteric, bladder
C Stage 4- Individualized treatment e usually palliative in intent and bowel damage.

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Bladder dysfunction with voiding difficulties and bladder computer generated plans based on CT images and more recently
hypotonia can occur due to damage to the hypogastric nerves MRI images of the tumour. The dose of radiation delivered to the
that lie in the uterosacral ligaments and parametria. A catheter is pelvis by external beam radiation is approximately 50.4 Gy. A
usually placed for 48 h following the procedure and bladder pelvic side wall boost of 5.4 Gy can be given if the lymph glands
emptying is checked on removal of the catheter. Care is taken look involved with disease on imaging.
during the surgery to preserve the nerves but more radical pro- In the sixth week, brachytherapy is delivered by insertion of
cedures for bigger tumours will inevitably cause some hypogas- applicators into the cervical canal. The applicator is attached to
tric nerve damage. an ‘after-loading’ device that delivers a pellet of iridium. The
Lymph node dissection for staging: lymph node dissection for iridium is left in the cervical canal for 30 min. This is known as
staging is recommended for all but the earliest stages of cervical high dose rate brachytherapy. The radiation dose is increased 90
cancer undergoing primary surgical treatment. It is approached Gy to the cervix by the brachytherapy.
abdominally via open, laparoscopic or robotic surgery, depend- Chemotherapy is cisplatin, given once a week for 6 weeks
ing on the primary surgery. The pelvic lymph node groups that during the course of radiation.
are removed include the common, internal, external iliac groups Worse tumour control and survival occurs if the treatment
and the obturator. nodes Presacral nodes are included by many takes longer than 8 weeks or if the patient becomes anaemic with
centres. Para-aortic lymphadenectomy can be used to identify an Hb less than 100.
patients with spread outside the pelvis that need extended field Risks of chemoradiotherapy e pelvic organs receive a signif-
radiotherapy (pelvis þ para-aortic area). PET/CT is used for this icant radiation dose resulting in acute and late toxicities. Acute
purpose also. radiation proctitis with symptoms of diarrhoea, rectal bleeding,
urgency, and tenesmus is frequently experienced during
Complications include primary haemorrhage and damage to the radiotherapy.
obturator or genitofemoral nerves. A significant late chronic Late toxicities occur after 3 months following radiotherapy
complication is lymphoedema of the mons pubis, groin and leg. and are due to small vessel damage with endothelial damage and
This occurs in 10% of women and is severe in 1%. inflammation. Symptoms can be continued diarrhoea, rectal
Sentinel lymph nodes in cervical cancer e the sentinel lymph bleeding, urinary frequency, haematuria. Very late effects can be
node is the first lymph node receiving lymphatic drainage from fistulation due to tissue ischaemia and necrosis.
the tumour. If negative the remaining lymph nodes are deemed Hormones and Fertility Issues e the ovaries are very sensitive
to be clear and do not need removal. The sentinel node is to radiation and lose their function permanently after the first
assessed by the pathologists using ultrastaging, whereby many few fractions of treatment. Hormone replacement should be
more slices of the lymph nodes are reviewed than when assess- offered to premenopausal women in the first week of radiation
ing all the nodes in a full lymph node dissection. Removing only treatment. This should be continuous combined HRT. Bleeding
the sentinel node rather than a block dissection of all the regional from any endometrium that survives radiation may be trapped by
lymph glands reduces the risk of lymphoedema. Sentinel node cervical stenosis caused by the tumour and post treatment
surgery is standard practice in breast cancer, and in vulval can- fibrosis.
cer. The application and validity of sentinel lymph node surgery The uterus is permanently affected by the level of radio-
in cervical cancer is not yet fully established in routine clinical therapy required in cervix cancer treatment, and cannot subse-
practice. quently carry a pregnancy.
Meta-analysis of case series shows that the sentinel lymph Egg collection with freezing of eggs or embryos can be offered
node detection rate and the negative predictive value are both prior to treatment. This usually takes 3 weeks to stimulate the
high in cervical cancer. Blue dye and technetium isotope or a ovaries to allow collection of mature oocytes. As the uterus is
fluorescent dye called indocyanine green (ICG) can be used. The permanently affected by the radiation, a surrogate is required.
sentinel lymph node is assessed with standard H&E staining Surrogacy is legal in the UK.
detects which detects metastases of 2 mm size. Immunohisto- Ovarian transposition is a surgical procedure that moves
chemistry (IHC) is also used with can detect individual tumour the ovaries from their position in the pelvis to the paracolic
cells. A randomized international trial is currently underway to gutters high up in the abdominal cavity, minimizing the ef-
evaluate the effectiveness of the sentinel nodes in cervical cancer fects of radiotherapy, whilst maintaining their blood supply.
surgery in terms of oncological outcomes (Senticol III). This can be performed laparoscopically and may be consid-
ered prior to commencing treatment. Chemotherapy agents
Non surgical treatments can affect ovarian function, but cisplatin has a small negative
Primary chemoradiotherapy: five randomized clinical trials effect only. This procedure results in ovarian function pres-
demonstrated a 6 % and 8 % improvement in absolute 5-year ervation in 30e50% of patients. The risks of the procedure are
survival and disease-free survival with chemo-radiotherapy ovarian metastases (approximately 1% usually in adenocar-
compared to radiation alone, and therefore in 1999 this became cinomas) and symptomatic ovarian cyst formation in 0e27%.
the new standard of care. As ovarian function is not guaranteed, egg collection and
Radiation is a combination of external beam radiotherapy freezing should be considered in addition or as an alternative.
(EBRT) and vaginal brachytherapy (BT). If the transposed ovaries function, hormone replacement
External radiation is given for 5 successive days each week for therapy is not needed, and there is the possibility of ovarian
5 weeks. Each daily session lasts 30 min. Linear accelerators stimulation and egg collection after the chemoradiotherapy is
produce Gamma rays that are directed into the pelvis along completed.

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Neoadjuvant chemotherapy: neoadjuvant chemotherapy surgery involving pelvic blood vessels, musculature and nerves.
before either standard concurrent chemo-radiation or radical This can be called a LEER procedure (laterally extended endo-
surgery in locally advanced cervical cancer is not a standard pelvic resection). PET/CT is used to exclude distant metastases
approach. Trials have shown varying success or failure with the prior to consideration of an exenteration.
approach. Two studies, the EORTC 55994 clinical trial on neo- The 5-year survival rate following exenterative surgery is 30
adjuvant chemotherapy followed by surgery, and the INTER- e60%. The prognosis is better for patients with a disease-free
LACE trial on neoadjuvant chemotherapy before concurrent interval >6 months, tumour size <3 cm and no pelvic side
chemo-radiation, are in progress. wall fixation. Pelvic extenteration requires careful assessment,
Adjuvant treatment after surgery: adjuvant (add on) treatment selection and work-up prior to proceeding.
after surgery is a combination of radiation and cisplatin, similar
to primary chemoradiation. Palliative treatment
Radiation consists of external beam radiotherapy (EBRT) and Stage 4 disease is usually incurable, and objective is symptom
vaginal brachytherapy (BT) but the brachytherapy is to the control and quality of life (palliation). Symptom control of pain,
vaginal vault using a different shaped applicator rather than a diarrhoea, constipation, shortness of breath, dysuria is impor-
cervical insertion (as the cervix has been removed at surgery). tant. Palliative chemotherapy is considered although the
The chemotherapy agent is cisplatin. response rates are worse in patients who have already received
chemotherapy. There are several regimens that are used in the
palliative setting including weekly paclitaxel, cisplatin/pacli-
taxel, cisplatin/topotecan, or cisplatin alone. Response rates are
Practice points 20e30% and survival is only approximately 7 months. Input
from palliative care physicians at an early stage is helpful.
C Adjuvant treatment after surgery is given if there is

Positive pelvic lymph nodes

Follow up
Parametrial invasion There is lack of evidence for any follow up regimes for patients
Involved/close surgical margins (<5 mm vaginal margins) with cervical cancer and no national guidelines. However, there
A high risk tumour: >4 cm, Lymphovascular space invasion, deep are some regional protocols. Generally appointments are offered:
invasion of cervical stroma by >1/2.
Every 3e4 months for years 1e2

Then every 6e12 months up to 5 years
C Primary chemo radiation is used for cancers of stage 1b3 and At the clinic appointment, a history is taken with respect to
above vaginal bleeding/discharge, weight loss, abdominal pain, and
C Adjuvant treatment and primary chemo radiation involve 5 weeks change in bowel habit or urination. An abdominal and pelvic
external beam radiation plus brachytherapy with weekly intra examination is undertaken including a speculum examination to
venous cisplatin. look for signs of recurrence. There is no evidence for the use of
C Complications following chemoradiotherapy include radiation cytology sampling in the follow up setting in cervical cancer
proctitis, and radiation effects on the bladder. Fertility is lost with unless a trachelectomy has been performed. Patients should be
the treatment. informed to seek medical review sooner should they experience
C HRT should be given to premenopausal women symptoms suggestive of recurrence in between their review
C Stage 4 disease is usually palliative and the primary objective is appointments.
symptom control and quality of life. As 90% of recurrences occur within 5 years most patients are
discharged after 5 years. A

Recurrent cervical cancer

If recurrence occurs, then 50% are within 2 years of initial pre- Practice points
sentation and the majority (50e60%) have disease outside the
pelvis which is incurable with a few exceptions. Treatment is C Follow up appointments are offered
individualized according to the site of the recurrence and the Every 3e4 months for years 1e2
time from the primary treatment. Then every 6e12 months up to 5 years

Exenterative surgery C If recurrences occur, 50% are within 2 years and the majority (50
Patients who relapse locally after chemoradiotherapy cannot e60%) have disease outside the pelvis which is incurable with a
receive further curative dose radiotherapy. If recurrence is few exceptions and therefore treatment is palliative.
confined to the pelvis, with no evidence of spread, the pelvic C Patients who relapse locally after chemoradiotherapy can be
exenterative surgery can be considered as an option for cure. considered for exenterative surgery as a potentially curative
Exenterative surgery involves removing the uterus and cervix (if approach
not already done so) along with affected organs. The bladder
(anterior exenteration), rectosigmoid colon (posterior exentera-
tion) or both bladder and bowel (total exenteration) can be
removed. Pelvic side wall disease can be resected using extended

OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 30:6 173 Ó 2020 Published by Elsevier Ltd.
 REVIEW

FURTHER READING Pelvic cancer surgery. In: Patel HRH, Mould T, Joseph JV, Delaney CP,
Bhatla N, Berek J, Cuello M, et al. New revised FIGO staging of cer- eds. Modern breakthroughs and future advances. New York:
vical cancer. Abstract S020.2. Presented at the. In: FIGO XXII World Springer, 2015.
congress of gynecology and obstetrics. Rio de Janeiro, Brazil, Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus
october 14-19, 2018, 2018;. https://doi.org/10.1002/ijgo.12584. Int abdominal radical hysterectomy for cervical cancer. N Engl J Med
J Gynecol Obstet 2018; 143(suppl.3). 2018; 379: 1895e904.

OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 30:6 174 Ó 2020 Published by Elsevier Ltd.