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Benign conditions of the cervix:
Cervical ectropion
In women of reproductive age the columnar epithelium is visible on the ectocervix as a circular,
red area surrounding the external cervical os. This is a normal finding and should not be called
‘cervical erosion’ because this erroneously implies it is an ulcer. An ectropion commonly
develops under the influence of the ‘three Ps’: puberty, pill and pregnancy. The fragile,
glandular columnar epithelium of a large cervical ectropion may predispose to intermenstrual
and postcoital bleeding (IMB, PCB). Some women may present with an excessive, clear,
odourless mucus-type discharge. To reduce the ectropion and associated symptoms women
should be changed from oestrogen-based hormonal contraceptives. The other option is cervical
ablation where the visible glandular producing columnar cells are ablated, usually with
cryocautery, as an outpatient. Prior to treatment end, cervical and lower genital tract swabs are
taken to exclude chlamydia and other sexually-transmitted infections and normal cervical
cytology should be confirmed to exclude cervical premalignancy and malignancy.
Nabothian follicles
Sometimes the columnar glands within the transformation zone become sealed over, forming
small, mucus-filled cysts visible on the ectocervix. These are termed ‘nabothian follicles’ and
are of no pathological significance. No treatment is usually required although extremely large
ones can be drained using a large-bore needle.
Cervical polyps
Cervical polyps are benign tumours arising from the endocervical epithelium and may be seen
as smooth, reddish protrusions. They are usually asymptomatic, being identified incidentally
during a routine cervical smear, but as with a cervical ectropion they can cause vaginal
discharge, IMB and PCB. They are easily removed by avulsion with polyp forceps as an
outpatient.
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Cervical stenosis
Cervical stenosis refers to pathological narrowing of the endocervical canal and is usually an
iatrogenic phenomenon caused by a surgical event. Treatment of premalignant disease of the
cervix using a cone biopsy or loop diathermy can cause cervical stenosis, as can endometrial
ablation affecting the os. The ensuing trapped blood in the uterus (haematometra) causes
cyclical dysmenorrhoea with no associated menstrual bleeding. Treatment is by surgical
dilatation of the cervix under ultrasound or hysteroscopic guidance.
Premalignant disease of the cervix:
Introduction
Cervical screening has been shown to reduce both the incidence and the number of deaths from
cervical cancer in higher income countries.
Epidemiology and aetiology
Cervical cancer is caused by persistent high-risk HPV infection. HPV is a small, double-
stranded deoxyribonucleic acid (DNA) virus of which there are more than 100 different types.
These are classified as low-risk or high-risk types, depending on their ability to cause cancer.
Low-risk types HPV 6 and 11 cause benign warts, while high-risk types HPV 16, 18, 31, 33 and
45 cause cervical cancer. HPV infection is spread during sexual intercourse. Infection is very
common following the onset of sexual activity and up to 80% of adults show serological
evidence of previous infection. Infection is usually transient and of no clinical consequence, but
a minority of individuals develop a persistent genital infection that predisposes them to
premalignant and malignant change. Smoking reduces the efficiency with which the virus is
cleared by the immune system and increases the risk of persistent infection. Women who are
immunocompromised, for example those with human immunodeficiency virus (HIV) and
transplant recipients on long-term immunosuppressive therapy, are particularly at risk of
premalignant and malignant disease of the cervix.
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Pathophysiology
The tubular cervix is composed of stromal tissue covered by by squamous epithelium in the
vagina (ectocervix) and columnar epithelium within the cervical canal (endocervix). The
endocervix contains many deep folds, called crypts, that are lined by columnar epithelium. The
meeting of the two types of epithelium is called the squamocolumnar junction (SCJ) and this is
usually on the ectocervix. The position of the SCJ varies throughout life. In children it lies at
the external cervical os, at puberty it extends outwards onto the ectocervix as the cervix
enlarges, and in adult life it returns to the external cervical os through the process of metaplasia,
which is the physiological transformation of columnar epithelium to squamous epithelium. The
so-called ‘transformation zone’ (TZ) is defined as the area between the original SCJ and the
current SCJ where the epithelium changes from columnar to squamous epithelium over time.
Sometimes the columnar epithelium is covered by squamous epithelium, leading to retention of
mucus – this is called a nabothian follicle.
The TZ is the site where premalignancy and malignancy develop.
When HPV infection persists in certain individuals, it triggers an oncogenic process in the
region of the TZ where metaplasia occurs. Integration of HPV DNA into the basal epithelial
cells leads to immortalization and rapid cellular turnover. This disordered immaturity within the
epithelium is called ‘cervical intraepithelial neoplasia’ (CIN) and is truly an intraepithelial
condition (cancer is diagnosed when this process breaks the basement membrane). Immature
cells are hyperchromatic with large nuclei, minimal cytoplasm and abnormal mitotic figures.
CIN is classified as either low-grade (CIN 1) or highgrade disease (CIN 2 and 3), depending on
whether the abnormal cells are seen in the bottom third or top two-thirds of the cervical
epithelium, respectively.
Natural history of CIN
Regression and progression of CIN may occur. Spontaneous regression of low-grade disease is
not uncommon and is likely to occur through the patient’s own cell-mediated immunity. This is
the argument for observational follow-up in patients with low-grade abnormality. High-grade
disease is less likely to regress spontaneously and requires treatment, as there is a risk of
progression to cancer. If left untreated, around 20-30 % of patients with high-grade
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abnormalities develop cancer of the cervix. Reasons for this remain unclear but may include
high-risk HPV types, reduced host immunity and smoking. There is a convincing link between
CIN and cancer of the cervix, as nearly all microscopic cancers of the cervix coexist with CIN.
Diagnosis and investigations
Cervical cytology
Cells exfoliated from the cervix can be examined under the microscope and this acts as a good
screening test. Originally the ‘Pap smear’ was introduced by Papanicolou, where cells were
removed from the cervix using a wooden spatula and placed on a glass slide and fixed. The Pap
smear has now been superseded by liquid-based cytology (LBC), whereby a small brush is used
to sample cells from the TZ and the brush head placed in fixative. This is then spun down and
the cellular aspect of the specimen examined under the microscope. For more than 95% of
women, cervical cytology is normal and normal squamous cells are seen.
Abnormal cervical cytology shows squamous cells at different stages of maturity (dyskaryosis).
Like CIN, cervical cytology is classified as low grade (minor cytological abnormalities showing
mild dyskaryosis or borderline change) or high grade (moderate and severe dyskaryosis).
There is some correlation between the grade of cytological abnormality and the extent of CIN
found on the cervix, but this is not totally reliable.
Cervical cytology triages patients to the colposcopy clinic for further assessment.
The sensitivity of a single cervical smear for high-grade CIN detection is between 40% and
70%; however, as there is slow progression for most women with CIN to cancer, if a lesion is
missed then this should be picked up on a subsequent test. Women who attend regularly for
cervical cytology have a very low risk of developing cervical cancer.
The role of HPV testing in cervical screening
High-risk HPV testing improves the sensitivity of cervical screening.
Its value lies in its extremely high negative predictive power, which means that if a woman
tests high-risk HPV negative, her risk of developing cervical cancer over the next 5–10 years is
exceptionally low. The majority of women (around 95%) have normal cervical cytology and are
placed on routine recall. Women with high-grade cytology (2%) are referred urgently for
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colposcopic assessment. Women with minor cytological abnormalities undergo reflex testing
with high-risk HPV. HPV-negative women are returned to routine recall, while high-risk HPV-
positive women are referred for colposcopy. Many countries, including the UK, are now
moving towards primary HPV screening; that is, testing all cervical cytology specimens for
high-risk HPV first, and carrying out reflex cytological assessment on those that test positive.
This will reduce the costs of the screening programme, since HPV testing is automated and
achieves a high throughput, while cytological assessment is manual and requires a skilled
workforce.
Cervical Screening Programme
The UK has offered population-based cervical screening since 1988. Women aged 25–64 are
invited every 3–5 years to take part in it
Colposcopy
Colposcopy is the examination of the magnified cervix using a light source. It is used for both
diagnosis and treatment. The application of acetic acid and iodine solutions highlights abnormal
areas of the cervix that can be biopsied. Areas of CIN lack intracytoplasmic glycogen and fail to
stain brown when iodine is applied. CIN is a preneoplastic process and the process of
angiogenesis (new blood vessel formation) is apparent in CIN when viewed through the
colposcope. If CIN is present, the colposcopist determines whether the appearances are low or
high grade. The latter can be treated in the clinic on the same visit (known as ‘see and treat’);
the former can be monitored with a subsequent colposcopy and cytology 6 months later. A
biopsy usually helps make the decision if unsure (‘select and treat’). All doctors and nurses
carrying out colposcopy are required to undergo a period of training and examination to ensure
high quality and standards of care are met. In addition, each colposcopy service undergoes a
rigorous external quality assurance assessment every 5 years to ensure high standards.
HPV vaccination
HPV vaccines have been shown to be safe and effective at preventing persistent high-risk HPV
infection CIN. School-based immunization in the UK is aimed at 12–13-year-old girls so it will
take many years to know if HPV vaccination can reduce deaths from cervical cancer. The
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bivalent vaccine prevents persistent infection with HPV types 16 and 18, which together are
responsible for more than 70% of cases of cervical cancer.
IMPORTANT POINTS
• Cervical cancer is now considered a preventable disease in countries where resources permit.
• Prophylactic HPV vaccination can prevent infection with high-risk HPV types that cause
cancers of the cervix and other lower genital tract sites.
• Regular screening by cervical cytology allows premalignant disease to be detected and treated
before it undergoes malignant transformation.
• Women who are treated for high-grade CIN are at increased risk of cervical cancer in their
lifetime compared to other women, but regular cervical screening will pick up residual or
recurrent disease that can be treated.