This document provides an overview of the anatomy, histology, staging, and pre-treatment workup for cancer of the cervix. It describes the anatomy of the cervix and surrounding structures. It discusses the histologic types and FIGO staging of cervical cancer. It also outlines the typical clinical presentation and evaluates the pre-treatment workup, including physical exam, imaging like MRI, CT, ultrasound, and biopsies to establish diagnosis and staging.

1. Anatomy & Pre-treatment
Work up of Cancer Cervix
Dr Chandrima Mukherjee
Junior Resident
Dept of Radiation Oncology
1

2. Anatomy
3

3. Sagittal Section through the Female Pelvis
4

4. Cervix
• It is the lower cylindrical portion on
the uterus.
• It is 3-4cm long, 2.5cm in diameter
slightly wider in the middle than at
either end
• Lower portion of cervix projects into
the anterior wall of the vagina which
divides it into supra-vaginal & vaginal
parts.
• The cervical canal opns into the vagina
by an opening called the external os.
• Cervix is least mobile portion of
uterus due to attachment of ligaments
Pg 387, B D Chaurasia, 6th Edition, Volume 2 5

5. • Supravaginal Part of cervix:
• Related anteriorly to the bladder
• Post to the POD, containing coils
of intestine & to rectum
• On each side, to ureter & to
uterine artery, embedded in
parametrium.
• Vaginal Portion of cervix projects
into the anterior wall of vagina.
The spaces b/w it & the vg wall
are called the vaginal fornices.
6

6. • Uterus is a pear-shaped muscular organ,
divided into fundus, lower uterine segment
and cervix uteri.
• The uterus has three tissue layers which
include the following:
• Endometrium: the inner lining and
consists of the functional (superficial)
and basal endometrium. The
functional layer responds to
reproductive hormones and shedding
results in menstrual bleeding.
• Myometrium: the muscle layer and is
composed of smooth muscle cells.
• Serosa/Perimetrium: the thin outer
layer composed of epithelial cells.
7

7. Angles of Uterus
Angle of Anteversion
• Forward angle formed by long
axis of vagina and long axis of
cervix at the level of external
os ~ 90 Degrees
Angle of Anteflexion
• Forward angle formed by long
axis of uterus and long axis of
cervix at the level of internal
os ~ 170 Degrees

8. Parametrium
• Parametrium refers to the areolar connective tissue located between the
uterine corpus and pelvic side wall, cranial to ureter and surrounding
uterine artery.
• Ureters are the anatomical landmark for the lateral parametrium. The
proximal lateral parametrium is identified medially to the ureter, while
the distal lateral parametrium is identified laterally to the ureter
Axial T2 Weighted MRI Image of Parametrium

9. • Components of Parametrium –
• Ventral Parametrium - Vesicouterine
ligament (the uterine branches to
ureter)
• Lateral parametrium - Uterine
vessels, uterine lymph nodes and
ways.
• Dorsal parametrium - Sacrouterine
ligament
• Ventral paracolpium - Vesicovaginal
ligament (the anastomosis between
vaginal vessels and inferior vesical
vessels)
• Lateral paracolpium - Vaginal vessels
and vaginal lymph nodes and ways
10

10. Broad Ligament
• Contents:
• Uterine Tube
• Round Ligament of Uterus
• Ligament of Ovary
• Uterine Vessels near its attachment to
the uterus
• Ovarian Vessels in the infundibulopelvic
ligament
• Uterovaginal & Ovarian Nerve Plexuses
• Epoophoron
• Paroophoron
• Lymph nodes & lymph vessels
• Dense connective tissue or parametrium
present on side of the uterus
11
Pg 385, B D Chaurasia, 6th Edition, Volume 2

11. • Peritoneal Ligaments
• Anterior Peritoneal Ligament-
uterovesical Fold
• Posterior Peritoneal Ligament –
rectovaginal fold
• Rt & Left Broad ligaments – Attach
the uterus to the lateral pelvic wall
• Fibromuscular Ligaments
• Round Ligament of uterus
• Transverse Cervical Ligament
• Uterosacral ligament
12
Ligaments of Uterus
Pg 385, B D Chaurasia, 6th Edition, Volume 2

12. 13

13. Delancey’s Levels of Supports

14. Blood Supply
• Arterial Supply:
• Uterine Artery ( Br of Int Iliac Art)
Branches of the uterine artery:
n Ureteric
Descending vaginal—these unite to form the
anterior and posterior azygos artery of the
vagina
n Circular cervical
n Arcuate  radial  basal  spiral and straight
arterioles of the functional layer of the
endometrium
n Anastomotic with the ovarian artery
• Ovarian Artery
• Venous Supply
• Parametrial Veins
• Drains Into uterine vein – Int Iliac
Vein
B D Chaurasiya’s Human Anatomy, 6th Edition 15

15. 16

16. NERVE SUPPLY
• Nerve Supply
 Sympathetic - Inferior thoracic spinal cord segments -> Lumbar
splanchnic nerves and pelvic-hypogastric-intermesenteric series of
plexus
 Parasympathetic - S2 to S4 spinal cord segments -> Pelvic
Splanchnic nerves -> Uterovaginal-inferior hypogastric plexus
17

17. 18

18. HISTOLOGY Squamo-Columnar Junction is defined as the
border between the stratified squamous
epithelium and the mucin-secreting
endocervical epithelium.
Morphogenetically, there are two SCJ.
Original SCJ - seen at birth.Subsequently,
with puberty, sexual activity and pregnancy
there is ‘ectopy’ of the endocervical
epithelium which undergoes squamous
metaplasia resulting in the formation of ‘New
SCJ’ which is more cranial to the original SCJ.
The region between the original and new SCJ
is the Transformation Zone or TZ.
This concept is extremely important for
understanding the pathogenesis of cervical
cancer because virtually all of these lesions
originate here.
19

19. Lymphatic Trapezoid of Fletcher
• A line is drawn from junction of S1-S2 to the top of symphysis pubis.
• Then a line is drawn from the mid point of that line to the anterior aspect of L4
• A trapezoid is constructed in a plane passing through the transverse line in the
pelvic brim plane and the midpoint of the anterior aspect of the body of L4
• A pt 6 cm lateral to the midline at the inferior end is used to give an estimate of
dose to the mid-external Iliac Lymph Nodes (labelled R. EXT & L.EXT for right and
left external respectively)
• At the top of the trapezoid, points 2 cm lateral to the midline at the level of L4
are used to estimate dose to the low para-aortic areas (labelled R.PARA
• Midpoint of a line connecting these 2 points is used to estimate the dose to the
common Iliac Lymph nodes (labelled R.COM & L.COM)
20

20. 21

21. Ca Cervix
22

22. Global Scenario: Females
23

23. The Indian Picture!
24
• In India, cancer of the cervix uteri
is the 3rd most common cancer
with an Incidence rate of 18.3%
(123,907 cases) and the second
leading cause of death with a
mortality rate of 9.1% as per
GLOBOCAN 2020
• Highest – Tamil Nadu
• Lowest – Jammu & Kashmir

24. 25

25. Risk Factors
• HPV infection is associated with >90% of cervical cancer cases.
• HPV 16/18 confer highest risk of carcinogenesis and account for 65% to 70% of cases (other cancer-causing
strains are 31, 33, 45, 52, 58)
• Other risk factors
• Smoking (RR-1.55)
• Immunocompromised status (Post-transplant, AIDS)
• History of STDs
• Young age at first sexual intercourse (RR-1.75)
• Multiple Sexual Partners (Promiscuity)
• Multiparity
• Low Socioeconomic Status
• DES exposure in utero (associated with clear cell adenocarcinoma of cervix/vagina, 0.14 -1.4 per
1000)
• Family History of cervical cancer
• Long-term use of oral contraceptives
26

26. Human Papillomavirus (HPV)
27

27. Natural History of HPV infection: Surrogate
Markers for Cervical Cancer
28

28. HPV - Pathogenesis
• Bosch et al. noted that HPV 16 predominated in
squamous-cell carcinoma, whereas in
adenocarcinoma and adenosquamous carcinoma
HPV 18 predominated.
• MOA: HPV genome integrates into host cell
chromosomes in cervical epithelial cells and codes for
6 early and 2 late open reading frame proteins of
which 3 alter the cellular proliferation (E5,E6,E7).
• E6 and E7 are typically seen in HPV positive cervical
cancer cells.
• E6 protein inactivates p53 -> chromosomal instability
-> inhibits apoptosis -> activates telomerase.
• E7 protein affects retinoblastoma (Rb) protein -> loss
of regulation of cell’s proliferation-> Immortalization.
Bosch FX, de Sanjosé S. Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of causality. J Natl Cancer Inst Monogr
[Internet]. 2003 [cited 2022 Jul 19];2003(31):3–13. Available from: https://pubmed.ncbi.nlm.nih.gov/12807939/

29. Histopathologic types
• The histopathologic types, as described in the World Health
Organization’s 2014 Tumours of the Female Reproductive
Organs are
1. Squamous cell carcinoma (keratinizing; non-keratinizing; papillary,
bas-aloid, warty, verrucous, squamotransitional, lymphoepithelioma-
like)
2. Adenocarcinoma (endocervical; mucinous, villoglandular,
endometrioid)
3. Clear cell adenocarcinoma
4. Serous carcinoma
5. Adenosquamous carcinoma
6. Glassy cell carcinoma
7. Adenoid cystic carcinoma
8. Adenoid basal carcinoma
9. Small cell carcinoma
10.Undifferentiated carcinoma
90%
10%
1-2%

30. FIGO 2018 Staging
31

31. Manganaro, L., Lakhman, Y., Bharwani, N. et al. Staging,
recurrence and follow-up of uterine cervical cancer using
MRI: Updated Guidelines of the European Society of
32

32. Diagrammatic representation of various anatomic stages of carcinoma
of the uterine cervix, according to the FIGO classification. Stage IIA has been divided
into stage IIA1, with tumors invading into the upper vagina but ≤4 cm in size, and stage IIA2, with tumors >4 cm in size. 33

33. Revised Staging – 2021
• A corrigendum to the 2018 staging was published thereafter, with
some modifications.
• The horizontal dimension of a microinvasive lesion is no longer considered.
• Tumor size has been stratified further into three subgroups: IB1 ≤2 cm, IB2 >2–≤ 4
cm, and IB3 >4 cm.
• Lymph node positivity, which correlates with poorer oncologic outcomes assigns the
case to Stage IIIC—pelvic nodes IIIC1 and para-aortic nodes IIIC2.
• Micro-metastases are included in Stage IIIC.
For Stage IIIC: Adding rotation ‘r’ for radiology and ‘p’ for pathological to indicate method of
detection. Eg: Stage IIIC1r or IIIC1p

34. • Grading by any of several methods is encouraged, but it is NOT a basis for modifying the
stage groupings in cervical carcinoma.
G1 - Well Differentiated G2 - Moderately Differentiated G3 – Poorly Differentiated
 GRADING – FIGO 2018

35. Pre-treatment Work-Up in a Ca
Cervix
36

36. Clinical Presentation
• Asymtomatic/ symptomatic
• Asymptomatic in early stages : Incidentally diagnosed through screening
procedure
• Symptoms: 1. Abnormal Vaginal Bleeding -
2. Discharge
3. Urinary Symptoms
4. Rectal symptoms
5. Pedal Edema
6. Pain: Dyspareunia, Low backache, deep pelvic Pain, sciatica
37

37. SYMPTOMS
BLEEDING/DISCHARGE BOWEL BLADDER PAIN
Post coital bleeding Constipation
(bowel
obstruction)
Burning
micturition (UTI)
Lower abdominal pain d/t UTI
Menorrhagia Rectal bleeding
(advanced cases
Increased
frequency
Lumbosacral pain
(Paraaortic LN with lumbosacral roots
extension or HUN)
Metrorrhagia Hematuria
(advanced cases)
Dyspareunia
Symptoms related to anaemia (fatigue)
in chronic bleeding
Hypogastric/pelvic pain (Tumour necrosis
or associated PID)
Foul smelling serosanguinous or
yellowish vaginal discharge
Leg pain and swelling (Persistent edema of
lower extremities due to lymphatic/venous
blockade by pelvic sidewall disease)
38

38. Signs
• Per speculum/ per vaginal/ per rectal examination
• Abnormal appearance of cervix, vagina due to erosion, ulcer or tumour.
• Visible lesions present with exophytic growth or barrel shaped cervix
(endocervical) .
• Rectal examination  mass/ bleeding due to erosion.
• Bimanual palpation may reveal pelvic bulkiness/ masses due to pelvic
spread.
• Pedal oedema  lymphatic or vascular obstruction or DVT
• Pallor  chronic bleeding per vaginum, haematuria, bleeding per rectum.
• Supraclavicular LN metastatic disease.
39

39. Procedure – PER-VAGINAL EXAMINATION
Patient is asked to void and empty bowel prior to examination. Consent is taken after explaining examination procedure
Patient is placed in lithotomy / comfortable position
Inspection of Lower Abdomen & External Genitalia for masses / tenderness / distension / incisions.
Lubricated Fingers of dependent hand are run through anterior vaginal wall to look for paraurethral induration followed
by posterior vaginal wall to look for rectocele / enterocele.
Warm & moist bivalved speculum is inserted for inspection of cervix and removed.
Lubricated fingers in vagina to note the consistency and location of cervix (lesion) and followed by bimanual
examination with the other hand placed above the symphysis.
Examination with the middle finger of the same hand placed in rectum to assess for the involvement of parametrium
While removing fingers, entire circumference of rectum is felt and glove is inspected for evidence of mucus / discharge /
fresh blood.

40. Mahantshetty U, Poetter R, Beriwal S, Grover S, Lavanya G, Rai B, et al. IBS-GEC ESTRO-ABS
recommendations for CT based contouring in image guided adaptive brachytherapy for cervical
cancer. Radiother Oncol. 2021 Jul 1;160:273–84. 41

41. 42
Pre-treatment
Evaluation
Biochemical
Fitness
Investigations for
Diagnosis
Investigations for
Staging (
Clinicoradiological)
Pelvic Exam/EUA with clinical
diagrams
CT TA + MRI Pelvis – locoregional
assessment
Cystoscopy/Proctoscopy if req
PET/ USG based on clinical susp of
mets
CBC
RFT
LFT
Coag Profile
Viral Markers
Biopsy- Punch/
Colposcopic
Guided

42. • Imaging evaluation may now be used in addition to clinical
examination where resources permit. The revised staging
permits the use of any of the imaging modalities according to
available resources, i.e. ultrasound, CT, MRI, positron emission
tomography (PET), to provide information on tumor size, nodal
status, and local or systemic spread.
• Chest radiography in PA and lateral views is performed in
patients with local-regionally advanced disease to evaluate for
pulmonary metastases.
Imaging in Carcinoma Cervix – FIGO 2018

43. • Trans-Vaginal Ultrasound (TVS) with high frequency (7-9
MHz) transducer maybe used for assessment of local
spread of tumor into stroma / parametria, in patients
suspected of having early stage disease.
• In patient suspected of having advanced disease,
transabdominal US can be used to evaluate
Hydronephrosis.
• Ultrasound (US) has a primary role in assisting with
intracavitary brachytherapy applicator insertion and may
detect uterine perforation, allowing for proper
positioning, which is critical for adequate dosing and
affects survival

44. • CT Imaging is usually suboptimal for assessing
tumor extent of central pelvic spread and
accurate measurement, since tumor is usually
homogenously enhancing similar to normal
cervical tissue.
• For diagnosing LN involvement, acceptable
size of cut-off value ranges between 0.8-1.0
cm in Short Axis Diameter. Other features like
density, round shape and loss of fatty hila are
incorporated for diagnosis.
• Chest CT findings of metastases are
pulmonary nodules or involvement of the
supraclavicular nodes.
Imaging in Carcinoma Cervix – FIGO 2018

45. • The overall accuracy of CT scanning in staging cervical cancer ranges
from 63% to 88%.
• In the detection of lymph node abnormalities, the overall accuracy of
conventional CT scanning is 77% to 85%, with sensitivity of 44% and
specificity of 93%
• The CT scan is more valuable in evaluation of the PALNs (specificity of
100% and sensitivity of 67%).
46

46. • MRI is the best method of radiologic assessment of
primary tumors greater than 10 mm.
• Multiplanar fast spin-echo T2 images help evaluate for
tumor invasion into the parametria (stage IIB) and pelvic
sidewall (stage IIIB), and images after gadolinium-based
contrast agent administration help assess for peritoneal,
nodal, and bone metastases.
• Tumor is of intermediate signal intensity (Lower than fat
& higher than myometrium / stroma) on T2-weighted
images.
• Diffusion-weighted imaging, when added to conventional
MRI sequences, improves lesion detection
• Disdavantage: Postbiopsy inflammatory changes can
cause false positives by overestimating the size and
extent of parametrial invasion
Imaging in Carcinoma Cervix – FIGO 2018 & RSNA 2019

47. 0
48

48. • PET-CT Imaging is best used to
evaluate hydronephrosis,
retroperitoneal lymphadenopathy &
distant metastasis.
• A lymph node is considered positive
for metastasis when it is within the
anatomic nodal drainage pathway for
the primary tumor and demonstrates
tracer uptake greater than that of a
clearly a normal node elsewhere on
the scan
• Distant metastases noted at PET/CT
should be confirmed with pathologic
analysis.
• PET scanning had a sensitivity of 75%
and a specificity of 92% in detecting
para-aortic metastasis
Imaging in Carcinoma Cervix – FIGO 2018 & RSNA 2019

49. 50

50. 51

51. Screening
• Pap Smear Screening:
• ACOG 2015- < 21 yrs- No screening
• 21-29 yrs – Pap Smear Alone- screening every 3 yrs
• If >/ 3 consecutive Normal Pap Smears & No history of CIN 2, CIN 3, DES
exposure, or HIV infection and the women is not immunocompromised,
screening should be every 3 yrs
• 30-65 yrs: Co- testing of Pap Smear with HPV DNA test for low risk women
every 3 years
• >65 yrs – No screening if adequate prior screening negative & low risk
52

52. • Women who had a hysterectomy for benign reasons and no history of
HGSIL – discontinue testing
• Women treated already for CIN-II, CIN-III need annual screening for at least
20 years.
• Hysterectomy and history of CIN2/3 – to undergo annual pelvic exams.
• If smear shows atypia or mild dysplasia (class II), it should be repeated >/=
2 weeks after the initial test to allow representative cellular exfoliation to
occur.
• In High Risk cases (HIV+ / Immuno-compromised), regular co-testing is
advised.
• Screening is recommended for candidates who have been administered
HPV Vaccine
53

53. Screening – Pap Smear

54. Cervical intraepithelial neoplasia (CIN) refers to an abnormal growth / lesion that can progress to invasive carcinoma.

55. Vaccination
• Age-specific cross-sectional HPV prevalence peaks at 25% in
women aged less than 25 years, which suggests that the
infection is predominantly transmitted through the sexual route.
• Thus, prophylactic HPV vaccination as a preventive strategy
should target women before initiation of sexual activity, focusing
on girls aged 10–14 years.
• There is evidence for the effectiveness of vaccination at the
population level in terms of reduced prevalence of high-risk
HPV types, and reduction in anogenital warts and high-grade
cervical abnormalities caused by the vaccine types among
young women
56

56. HPV - Vaccination
Vaccine Cervarix Gardasil Gardasil-9
HPV Strains 16, 18 6,11,16,18 6,11,16,18, 31, 33, 45, 52, 58
Schedule & Recommendations:-
• Routine Vaccination – For all males & females aged 9-12 years. Two doses of
HPV vaccine (0.5 mL) should be given at 0 and at 6 to 12 months.
• Catch-up Vaccination – For all males & females aged 13-26 years. Three doses
of HPV vaccine should be given at 0, 1 to 2, and 6 months.
• For age >27 years, catch-up vaccination is not routinely recommended,
administered in high-risk individuals (healthcare workers, exposure to multiple
sexual partners).
• Vaccination is administered irrespective of age in immunocompromised individuals.