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Anatomy & Physiology of the

Cervix
Cervical Cancer Prevention Training
Anatomy and Histology

Objectives
1. Describe female pelvic anatomy and epithelial layer of the cervix
2. Describe normal physiological changes of the cervix during a
woman’s life cycle
3. Describe or identify areas most likely to develop precancerous
abnormalities
Female Pelvic Anatomy
1. Perform examination, screening and
Understanding the
diagnosis
anatomy enables one to
2. Interpret laboratory reports
3. Complete treatment procedure
reports
4. Understand and implement clinical
recommendations received from
providers in the higher levels of the
healthcare system
5. Educate patients and their families
External Female Genitalia

• Labia majora and minora


• Clitoris
• Urethra
• Introitus
Internal Female Genitalia
• Vagina
• Uterus
• Fallopian tubes
• Ovaries
• Bladder
• Urethra
Internal female genitalia

From Wikibooks: Human Physiology/The female reproductive system


Female Internal Genitalia

From Everyday Health


Vagina

• Elastic fibromascular tube from the introitus (vaginal opening) to


the cervix
• Multiple folds on the walls allow expansion during intercourse
and child birth
• Ectocervix protrudes into the upper end of the vagina (anterior,
posterior and lateral fornices)
Uterus
• Thick walled, pear shaped hollow • Cavity of the uterus lined by the
organ made of smooth muscle endometrium
• Pelvic support comprised of • Normal uterus measure
connective tissue structures: approximately 10cm from fundus
o Transverse ligaments to cervix

o Uterosacral ligament • Exceptions are caused by


pregnancy or tumours
o Broad ligament: ovaries
attached to the back of the
broad ligament
Cervix
• Forms the lower third of the uterus
• Composition:
o Dense fibromuscular tissue
o Lined by two types of epithelium
• Measures 3 cm by length and 2.5 cm in diameter
• Ectocervix lies within the vagina and is visible with speculum
Cervix
• Upper two thirds lies above the vagina
• Cervical canal runs through the centre from the internal os to
the external os which is visible with the speculum
• External os is seen as a small round opening in nulliparous
women and wide, mouth-like, irregular slit in parous women
o Nulliparous = never given birth
Uterus and Cervix
Uterus and Cervix
Blood Supply and Lymphatic Drainage

• Arterial supply derived from internal iliac arteries


• Cervical branches descend along the entire cervix at 3 and 9
o’clock position (vital knowledge for injecting local anaesthetic)
• Veinous drainage runs parallel to arterial supply
• Lymphatic drainage runs close to the pelvic vessels (may act as
a pathway for cervical cancer spread)
Uterus and Cervix
Nerve Supply

• Ectocervix: no pain nerve endings


o Hence, procedures involving this area are well tolerated without
anaesthesia (biopsy and cryotherapy)
• Endocervix: rich in sensory nerve endings and therefore
sensitive to painful stimuli
• Networks of nerve fibres are found around the cervix and
extend to the uterine body
Cervical Epithelia
Overview

• Lined by 2 types of epithelium (squamous and columnar


epithelium)
• Histological understanding is critical to understanding:
o Cytologic screening
o Colposcopy
o Biopsy results in the management and treatment of cervical neoplasia
• The epithelium gives rise to cervical neoplasia
Cervical Epithelia
Stroma

• Composed of fibromuscular • The blood vessels, lymphatic


tissue made of collagenous channels and cervical nerves
connective tissue and ground coarse through the stroma
substance • Stroma plays little role in
• Accounts for most of cervical cervical neoplasia, rather
mass and shape more important for obstetric
functioning
Cervical Epithelia
Squamo-columnar junction

• Cervix is covered by both columnar and stratified non-


keratinising squamous epithelium
• Squamo-columnar junction (SCJ)
o Where the above two epithelia meet
o Very important cytologic and colposcopic land mark as > 90% of
genital neoplasia arises from the SCJ
o Presumed to be embryologic junction of the Mullrian and Urogenital
sinus
Cervical Epithelia
Squamous Epithelium

• Similar to the vagina


• Lacks rete pegs and is generally smooth
• Colposcopic appearance - Appears featureless except for fine
network of vessels which is sometimes visible
• Relative opacity and pale pink colour is derived from multi-
layered histology and the location of the supporting vessels
below the basement membrane
Cervical Epithelia
Stratified Squamous Epithelium

• Stratified Squamous Epithelia:


• Multi-layered epithelium of increasingly flattened cells
• Normally covers most of the ectocervix and vagina
• Appears pale pink and opaque in premenopausal women
• Basal layer composed of round cells is attached to the basement
membrane (separates epithelium from fibromuscular stroma)
• Appears whitish pink in postmenopausal women due to fewer cell
layers and is prone to trauma (small haemorrhages and petechial)
Cervical Epithelia
Squamous Epithelium

Maturation and glycogenation of This explains why the epithelium


squamous epithelia is influenced appears atrophic after loss of
by ovarian hormones ovarian function with pallor
• Estradiol promotes maturation, and sub-epithelial point
glycogenation and desquamation haemorrhages from the
increasing vulnerability of the
• Progesterone inhibits superficial underlying vessels
maturation

The atrophic changes may be seen less dramatically with prolonged exposure
to progestins
Cervical Epithelia
Squamous Epithelium

• Glycogenation of mature epithelium gives rise to strong uptake of Lugol’s


iodine solution
o This helps to distinguish abnormal and normal tissue (basis for
Schiller’s test)
• Dysplastic or HPV infected epithelium shows arrested maturation with
incomplete or absent glycogenation
o Hence their inability to take up iodine staining
• Abnormal deposition of keratin layers may be seen in the upper layers of
the epithelium
Squamous Epithelium

Figure 4.5 Histology of Squamous Epithelium


From ASCCP
Cervical Epithelia
Columnar Epithelium

• Lines the cervical canal and extends outwards to a variable


proportion of the ectocervix
• Single layer of tall cells on the basement membrane
• Much thinner than squamous lining of the ectocervix
• Appears shiny red when viewed with endocervical speculum
Cervical Epithelia
Columnar Epithelium & SCJ

Original Squamo-Columnar Junction (SCJ) is seen as a sharp line


with a step due to the different thicknesses of columnar and
squamous epithelium
• Original SCJ varies with:
o Woman’s age
o Hormonal status
o Birth history
o Pregnancy status
o Oral contraceptive use
Cervical Epithelia
Columnar Epithelium and Glandular Epithelium
• Cephalad to SCJ
• Composed of single layer of mucin secreting cells
• This epithelium is thrown into longitudinal folds and invaginations that
make up the endocervical glands (not true glands)
• The folds and invaginations make cytologic and colposcopic
detection of neoplasia less reliable and problematic
• The complex architecture of the glands give the epithelium a papillary
appearance through Colposcope and grainy appearance upon visual
inspection
• Single layer allows for colouration of underlying vessels to be seen
easily hence the epithelium appears more red
Columnar Epithelium

Figure 4.6 Histology of Columnar Epithelium


From ASCCP
Glandular Epithelium

Figure 4.7 Histology of Glandular Epithelium


From ASCCP
Cervical Epithelia
Squamocolumnar Junction (SCJ)

• Junction between squamous and


columnar/glandular epithelium
• Often marked by a line of metaplasia
and its location is variable (hormonal
status and age influence position)
Cervical Epithelia
Squamocolumnar Junction (SCJ)

Variations in location of SCJ


• Perimenarch:
• SCJ located at or very close to external os
• Reproductive age:
• SCJ located on the ectocervix at variable distances from the external os
• Cervix and the endocervical canal elongates under oestrogen influence
• High estrogen levels due to pregnancy and oral contraceptive further promote SCJ
eversion ( more ant-posterior positions than 3 and 9o’clock positions)
• Columnar epithelium eversion unto the ectocervix is not necessarily symmetrical
hence might cause confusion and prompt referral for possible lesion
Cervical Epithelia
Location of SCJ

Reproductive age:
• Eversion of SCJ often referred to as ectropion or erosion
(erosion- misnomer and shouldn’t be used)
• At times SCJ is located in part or completely on vaginal fornices
• Due to epithelisation arrest before completion which usually
occurs on the anterior and posterior walls
Squamocolumnar Junction (SCJ)
Age Differentiation

Reproductive age
• SCJ Variant consistent with in-utero exposure to DES
• In some cases the entire cervical is covered by columnar epithelium
Perimenopause
• From this moment on or with prolonged exposure to strong progestogen
agents which cause atrophy, SCJ recedes up the endocervical canal
• Makes cytologic sampling less reliable and colposcopic examination of
SCJ most often difficult and VIA unreliable
Figure 4.8 Histology of Squamous Metaplasia and the transformation zone
From ASCCP
Squamous Metaplasia
Transformation Zone

When exposed to the acidic vaginal environment, columnar epithelium


is gradually replaced by stratified squamous epithelium
• This is termed squamous cell metaplasia and gives rise to SCJ
• Original Squamous and newly formed epithelium look identical
whereas newly formed SCJ is distinct from the old on examination
Transformation zone is the area between newly formed SCJ and the
old where columnar epithelium is being replaced by squamous
epithelium
Figure 4.9 illustration of the transformation Zone
a. Squamo-Columnar Junction at various stages
Figure 4.9 illustration of the transformation Zone
b. transformation zone
Significance of the Transformation Zone
Nearly all cervical neoplasia occurs This is because reserve cells
in the transformation zone (TZ) undergoing metaplasia are vulnerable
• Also true for adenocarcinomas to carcinogens like HPV virus
which are associated with adjacent • Due to peak metaplastic activity
high grade squamous disease, during adolescence and first
even though may rarely involve pregnancy, it is understandable that
endocervical canal early sexual debut and early first
pregnancy are known risk factors
Significance of the Transformation Zone
Colposcopy and Neoplasia

• It is of important that the colposcopist is able to identify and


evaluate the TZ
• Given a particular lesion, the more severe disease tends to
occur cephalad in the TZ, where epithelium is least mature
Transformation Zone
Colposcopy

In order for a colposcopic exam to be If these conditions are not met, then
deemed satisfactory or adequate the high grade lesion or cancer cannot
TZ must be visualised in its entirety, be surely ruled out
• All the way up to columnar • Importance of TZ explains why it is
epithelium & in 360 degrees of necessary to collect both
direction columnar and squamous
metaplastic cells on a pap smear
All areas involved in squamous
metaplasia are visualized • It implies the entire area at risk
has been sampled
Histology of the TZ
As cell hyperplasia progresses to several layers of thickness, the
following occurs:
• Columnar epithelium is pushed off and replaced
• This proliferation is seen as flattening and fusing of columnar
villi
• Areas of metaplasia are paler compared to the one cell thick
columnar epithelium
o Due to viewing of underlying blood vessels via several cell layers
Histology of the TZ
Metaplasia

• As cell hyperplasia progresses to several layers of thickness the


following happens:
• Metaplasia is seen as numerous small glassy islands, overlying the
columnar epithelium, as well as pale translucent ingrowths from the
original squamous epithelium
• These can be irregularly shaped and distributed around the TZ
• Can coalesce into sheets of metaplasia, often with a thin acetowhite line at
advancing border
Histology of the TZ
Metaplasia

• Immature metaplasia: can turn acetowhite, causing striking


frosting of these areas
• Mature metaplasia:
• Pushes outward relative to external os and shows gradient of maturity
• Most mature epithelium is densest with at most a trivial fine vascular
pattern and does not turn acetowhite, it has the highest level of
glycogenation , therefore iodine uptake
• Less mature metaplasia:
• May be pale acetowhite and may show fine vascular patterns that can
both be confused for low-grade lesions
Histology and Colposcopy of the TZ
Metaplasia

Nebothian’s cysts: formed when crypts of mucin secreting


columnar epithelium become covered by metaplastic
epithelium
Vessels overlying the cysts can be large
• May alarm the novice colposcopist, even though benign
Histology and Colposcopy of the TZ
Metaplasia

Most mature metaplastic epithelium probably has little neoplastic


potential, like that of original squamous epithelium
Congenital TZ: some women have large regions of acetowhite,
iodine-variable epithelium which extend unto both anterior and
posterior fornices
• Caused by squamous epithelium of arrested maturation laid
down during fetal development
• Has low neoplastic potential, but could be confusing to the
culposcopist
Histology and Colposcopy of the TZ
Precancer and Cancer

Development of precancer and • In the presence of persistent HPV


cancer
infection and other cofactors, the
• Stratified squamous epithelium metaplasic squamous cells of the TZ
provides protection from take on an abnormal appearance
infections and toxic substances o This is called cervical squamous
• Normally, the top layers are precancer (dysplasia)
continually dying and slough off • The cells later multiply in a disorderly
o The integrity of the lining is manner typical of cancerous change, to
kept by the formation of new produce squamous cell carcinoma
cells from the basal layer
Histology and Colposcopy of the TZ
Precancer and Cancer

In women using oral contraceptives, during pregnancy, and


during puberty the TZ on the ectocervix is enlarged
• Exposure to HPV at such times facilitates infection hence
associated with squamous cell carcinoma
• 90% squamous cell carcinoma from metaplastic squamous
epithelium of the TZ, 10% adenocarcinoma from columnar
epithelium of the endocervix
Summary
• Squamo-columnar Junction
• Cervix (SCJ)
• Above vagina and into lower • Located at the junction
portion of uterus of the columnar and stratified
• Composed of ectocervix, squamous epithelium 
internal os, external os, and • Arises from squamous cell
endocervix (cervical canal) metaplasia
• Position and histology varies
with age, hormonal status, birth • Transformation Zone
history, pregnancy status and • Between old and new SCJ
oral contraceptive use (columnar          squamous)
• SCJ & TZ are most likely to • Colposcopic exam: must
develop precancerous visualize entire TZ including
columnar epithelium in all
abnormalities  directions 
Questions?

Thank You

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