1. CERVICAL CARCINOMA

2. • Common cancer, only next to Breast Cancer.
• One of the major causes of cancer related
deaths in women of age (35-45)years in
developing countries.
• Nearly all forms of carcinoma are Squamous
cell Carcinoma.

3. PREDISPOSING RISK FACTORS
•
•
•
•
•
•
Early age at first intercourse(18years)
Multiple Sex Partners.
Male partner with multiple previous sex partners.
Persistent infection by Human Papilloma Virus.
Poor personal Hygiene & socioeconomic status.
STD, HIV infections, Herpes Simplex virus 2 infection or
Condylomata.
• Immunosuppresed Individuals,
• Progesterone use over 8 years.
• Smoking and drug abuse.
Smegma is not carcinogenic.
Spermatozoa may be carcinogenic because they provide
DNA to cervical cells.

4. Pathogenesis
Viral genome able to
integrate into host
genome & expess
protein that inactivate
tumor suppressor gene
Viral genome unable to
integrate into host
genome

5. Definitions
Dysplasia:- It is the disorderly but non neoplastic proliferation
of normal cells resulting in atypical features, eg:
-variation of cell size, shape and polarity.
- alteration in nuclear cytoplasmic ratio.
- large hyperchromatic nuclei with marginal
condensation of chromatin material and mitotic figures.
Metaplasia:- It is reversible change in which one adult cell is
replaced by another type of cell for adaptation.
Due to pH changes, hormonal effect infections and
mutagens, Columnar epithelium of Squamocolumnar
junction(Site of origin) transforms into Squamous cells.
And this can be the precursor of Dysplasia and malignancy.

6. Dysplasia
Mild Dysplasia
(CIN-I)
Moderate Dysplasia Severe Dysplasia
(CIN-II)
(CIN-III)
Carcinoma in Situ
LSIL
According to
Bethesda system
HSIL
HSIL
confined to inner
1/3rd of epithlium
occupy 50% of
epithlial thickness
occupy entire
thickness of
epithelium, with
intact Basement
membrane.
Invasive
Carcinoma
beyond Basement
Membrane

7. koilocytic atypia
progressive atypia
diffuse atypia

8. Invasive Cervical Carcinoma
• Epidermoid Carcinoma
-more common, 80%cases
- arises from stratified
squamous epithelium of
cervix.
May appear as
proliferative/ulcerative/flat
indurated areas.
• Endocervical Carcinoma
-less common
-arises from mucous
membrane endocervical
canal
- assosciated with use of OCPs
and progesterone.
- They remain confined to
cervical canal for a long time
causing barrel shaped
enlargement of cervix, later
they protrude from cervical
canal.

9. Mode of Spread
1)Direct-i) Lateral – parametrium, Meckenrodts ligament, lateral pelvic wall. Uteteric
obstruction
ii) Inferiorly – upper part of the vagina, inguinal lymph nodes.
iii) Superiorly – endometrium in 2-8 % cases.
iv) Posteriorly – along uterosacral ligament in which sacral plexus is involved
causing sciatica.
Nerve sheaths and ureteric wall are not penetrated by cancer cells.
Invasion to rectum is very rare because of Pouch of Douglas.
2.) LymphaticPrimary group of LN – paracervical, obturator, internal iliac & external iliac, sacral
grp
Secondary group of LN – common iliac, aortic, inguinal.
Distant metastasis to lungs, CVS, 25-30%.
Lymphatic spread is by embolism or by permeation.
3)Haematogenous spread –Contributes 5%
Cancer cells invade the BVs but not erode them.
Organs-lungs, liver, bone, kidney, brain.

10. Clinical Features
SYMPTOMS
- woman in 3rd and 4th decade of life.
- Menstrual problems
- irregular menses, menometrorrhagia.
- continuous bleeding
- post coital bleeding.
- Vaginal Discharge
-Is secondary to infection of the tissues or ulceration
-Watery in nature which is initially white
- Becomes yellowish & changes to dirty brown then blood
stained
-Odour due to saprophytic infection
May be the only symptom of ca cervix.

11. Late symptoms
are due to spread of disease
-Renal – frequency, dysuria, hematuria, renal colic, urinary
Incontinence because of fistula
-Rectal – tenesmus, diarrhea, proctitis.
-Pelvic symptoms – deep pelvic pain, low back ache, sciata,
Swelling of the leg due to blockage of the lymphatics.
-Terrible triad: sacral pain
U/L lymphoedema of the leg
U/L ureteric obstruction
-Late & bad prognosis
Anaemia, cachexia, anorexia, loss of weight

12. Signs
Earliest sign on speculum
-erosion
- infected ulcer
Ulcers - hardness, irregularity, bleeds on touch.
Once the disease is established, 4 cardinal symptoms
-induration
-friability
-fixity
-bleed on touch
Every lady with ca cervix a part from all clinical tests must undergo
per rectal examination to find out any infiltration/thickness of the
rectal mucosa.

13. Signs
Late Lesions:1) Exophytic growth-papillary & polypoidal types – 95%,
friable, cauliflower like lesion which has rough granular, hard surface
which bleeds on touch. The lesion has got typical smell because of
saprophytic infection.
2) Endophytic growth – could ulcerative or infiltrative or
nodular.
Uterus bulky due to pyometra in advanced stage, when cervix is
blocked by growth.
Rectal examination reveals thickened induration of uterosacral
ligaments.

14. Complications:
Pyometra
Fistula.
Ureteric obstruction-hydronephrosis, pyonephrosis
Uraemia-because of infection & obstruction of renal
system
Cause of death in lady with ca cervix:
Uraemia
Cachexia
Infections
Complications of surgery
Radiotherapy

15. Diagnosis
• Pap Smear
To reduce incidence of False Negative reporting following
procedures are added to Pap Smear
-- Endocervical scrape cytology
– HPV testing by Hybridization or PCR.
– Liquid Based Cytology.
– Visual inspection of Acetowhite Areas (VIA)
• Colposcopy directed Biopsy.
• Cervicography.
• Cone Biopsy.

16. Pap Smear
• Screening test with
Sensitivity:- 70-80%
and Specificity:- 9598%
• Offered to all women
above 21 years of age
who are sexually active
for at least 3years.

17. Pap Smear
Technique.
To sample the ectocervix, a wooden spatula is placed against
the external os and rotated 360 degrees.
To sample the endocervix, a cytobrush is inserted into the
external os and rotated.
The sample obtained by the spatula and cytobrush is spread
on a glass slide and immediately placed in a fixative,
usually 95% ethanol, fixed for 30 minutes, and then
stained with Papanicolaou stain.
The sample is stained using the Papanicolau technique in
which tinctorial dyes and acids are selectively retained by
cells.

18. Cytology of CIN seen in Pap Smear
Normal
CIS-I
CIS-II
CIS-III
There is Progressive reduction of size of Cytoplasm, and increase in Nuclear
Cytoplasm Ratio as the grade of lesion progresses, which reflects there is loss of
cellular differentiation on the surface of cervical lesion

20. False positive reporting
- Infection, Inflammatory or reparative
changes, and the effects of irradiation can
result in atypical smear results suggestive, but
not diagnostic, of CIN.
- In these cases, smears should be repeated in
3–6 months.

21. If the Pap Smear is Negative:
• It could be False Negative Reporting, 15-30%
chances, so in such case
Pap Smear is repeated annually for 3 consequtive
years, and if still negative, then
Pap Smear is repeated 3-5 yearly upto the
age of 50 years.
Pap test should not be done when a woman is
menstruating, because endometrial cells can obscure
cervical cells.
But it can be performed during a woman's menstrual
period, if the physician is using a liquid-based test.

22. Investigations..
1) Liquid Based Cytology:
Here, the plastic spatula(instead of wooden) is used
which is placed in liquid fixative (buffered
methanol), instead of directly smearing on a slide.
This removes blood, mucus, and inflammatory cells.
Suspended Cells are then sucked onto filter paper
and then smear is made and stained on glass
slide.

23. 2) Visual inspection of Acetowhite Areas (VIA)
- done where the facilities for Pap Smear is
not present.
Procedure:- 5% acetic acid solution is applied
on cervix, this dehydrates abnormal areas
(high nuclear material and protein) turning
them into acetowhite. Normal areas
containing glycogen remain normal.

24. 5% acetic
acid
Acetowhite
(abnormal)
Schiller’s
Iodine
Cervix
Unstained
(Normal)
Biopsy
Visual Inspection of Acetowhite Areas (VIA)
Mahogany
Brown
(Normal)
Cervix
Unstained
(Abnormal)
Biopsy
Visual Inspection with Lugol’s Iodine (VILI)

25. Colposcopy
• Colposcope is the instrument
that is inserted into vagina
and permits examination of
cervix and upper part of
vagina.
Aims:- To study cervix when Pap
Smear detects abnormal cells.
- To locate abnormal areas.
- To study extend of
abnormal lesion.
- To take Biopsy.
- Conservative surgery
following colposcopic
guidance.
- Follow up of conservative
therapy cases.

26. Technique
-Acetic acid (3.0% or 5.0%) is applied to the cervix.
This removes mucus and dehydrates cells.
The more protein in the cell, the whiter it becomes.
Dysplastic cells contain large nuclei with abnormally
large amounts of chromatin (protein). The application
of acetic acid coagulates these intracellular proteins
and makes them opaque and white. Hence, cells with
an increased nucleus to cytoplasm ratio appear
opaque on colposcopic examination.

27. Colposcope can visualise:
- Acetowhite areas,
- mosaics,
- punctuations,
- Abnormal vessels.

28. Pap Smear and Colposcopic Examination in
Post Menopausal Women
The test is often negative in them because of
- dry vagina, senile vaginits
- poor exfoliation of cells.
- indrawing of squamocolumnar junction.
So, oestrogen cream daily for 10 days or,
400µg misoprostol is used.

30. Other Investigations
1) Basic Investigations:- Hemogram, Urinalsis, Blood Sugar levels, LFT,
RFT, serum electrolytes, ABO & Rh typing, cystoscopy, Chest Xray,
ECG.
2) CT Scan and MRI:
can detect Lymph Node Enlargment more than 1 cm.
helps in Staging of tumor.
3) FDG-PET
can detect lymphnode involvement
can detect recurrence.
Mechanism:- FDG accumulates in the malignant tissue because
they exhibit greater glycolysis, resulting in increased tumour
contrast.
CT and MRI shows anatomical changes, PET shows Biochemical
Changes in the tissues.

31. Staging of Cervical Carcinoma

33. <

34. Differential Diagnosis
1) CervicitiesInfectious or Noninfectious cervicitis.
2) Endometrial Carcinoma
3) Pelvic Inflammatory Disease.
4) Vaginitis.
5) Vaginal cancer.
6) Metastatic cancer to cervix (rare)

35. TREATMENT

36. Treatment of preinvasive(Stage 0)lesion
1) Local destructive
• Cryotherapy
-done for small lesions, OPD procedure w/o Analgesia
-agents like N2O, CO2 are used, that causes crystallization of
intracellular fluid.
- Freeze-thaw-Freeze technique over 9 minutes.
- least painful and cheap.
- Advised to abstain from sexual intercourse for 4 weeks.
- Side effects- Profuse Discharge, Uterine Spasms
• Laser ablation
- also an OPD procedure, done under Local Analgesia under
colposcopic guidance.
- converts cellular water to steam, and explodes the cells.
- Minimal Bleeding, no infections, no scars, no indrawing of
squamocolumnar junction.

37. 2) Local excision
•
•
•
•
Conization with knife, laser
LLETZ (Large Loop Excision of Transformation Zone)
LEEP (Loop Electrosurgical Excision Procedure)
NETZ (Needle Excision of Transformation Zone)
-Done in immediate Postmenstrual phase, under Colposcopic
view under Local Anesthesia.
- preferred for young woman desiring future child birth.
- can cause- stenosis of cervix, Abortion, Preterm labour.

38. 3) Radical excision
• Hysterectomy
- older and parous lady.
- concurrent fibriods, DUB, or prolapse.
- if microinvasion persists.
- if recurrence occurs.
- if lady cannot comply for followup

39. Management of CIN
Pap smear
Class I
(normal)
Repeat yearly for
3yr and then 3-5
yrly until 50yrs
Class II
(inflammatory)
Class III
CIN I (LSIL)
Treat infection and
repeat in 3 months
Test for HPV
and f/u yearly
Normal
f/u as class I
Persistent repeat smear
Normal
Local Destruction
•Coagulation
•Cryosurgery
•Laser ablation
Lifelong follow up
Local excision
•Conization
•Laser conization
•LEEP
Follow up
Class IV
Moderate, severe
CIN II,III (HSIL)
Class V
Invasive carcinoma
Biopsy, Rx acc. to stage
Surgical or Radiation.
Colposcopy and biopsy
Persistent
(Rx as HSIL)
Radical excision
•Conization
•Hysterectomy with/out removal
• of vaginal cuff
Follow up

40. STAGE IA
• Large loupe electrosurgical excision (best)
-For preservation of reproduction. But
tumor cell free margin is a must, with
followup for 1 year.
• Hysterectomy (abdominal/vaginal): choice of
treatment because follow up in our setting is
difficult.

41. STAGE IB-2A
• Radical/Vaginal Hysterectomy
• Wertheim’s hysterectomy
(Thorough exploration of the abdomen, paraaortic LN biopsy,
removal of the entire uterus, both adnexa, pelvic LN, medial 1/3 of
the parametrium and upper 1/3 of the vagina)
•
Radiation following radical hysterectomy is
needed if
1. Bulky lesion>4cm
2. deep stromal invasion
3. LN enlargement
4. margin of tissue show cancerous cell

42. STAGE IIB, IIIA, IIIB, IV
Radiotherapy (traditional)
-Goal is to achieve cytotoxic dose to cervical
parametrium, pelvic nodes by external
radiation.
-Bladder and rectum should be protected.
• In case of III b, intra cavity radiation along
with external radiation.
• Bulky irregular tissue should be treated with
radiation

43. Concurrent chemotherapy is a radio sensitizer,
& results in improved overall survival compared
with radiation alone.
Vs
Surgical Therapy
• Applicable only to stage I &
Applicable to all stages of
IIA.
Carcinoma.
• Requires Operation
OPD procedure.
Theatre.
Ovaries cannot be preserved.
• Accurate Surgical Staging is
Vaginal Stenosis, fistula
possible.
formation occurs which are • Ovaries can be preserved.
difficult to treat.
• Concurrent uterine ,
Not applicable if Uterine or
ovarian pathology can be
ovarian pathology are
treated.
present.
Radiotherapy
•
•
•
•
•

44. 5year survival
•
•
•
•
•
CIN: good, >90%
IB, IIA: 87-90%
Stage III: 30-40%
Stage IV:- 14%
Survival is inversely related to the number and
location of lymph node metastases, especially
pelvic and para-aortic lymph nodes, Tumor size,
staging and raised CEA level.
• If chemotherapy is also used i.e cisplastin along
with radiation better survival rate.
• AdenoCarcinoma(1-5%): Treatment is
radiotherapy.

45. FOLLOW UP
• Every 3 mths for 1-2yrs because most Carcinoma
cervix recur between 24-36 mths after
treatment.
• During follow up: total physical examinations
including weight,
- bimanual examination,
- CXR,
- USG pelvis,
- Pap smear
• After 3yrs of treatment: follow up every 6mths
and after 5 yrs every year

46. RECURRENCE
-Development of sciatic pain, lymphoedema,
fistula are sure signs of Recurrence.
-Radiotherapy- Treatment of choice.
- Exenteration operation.
- Anterior Exenteration.
- Posterior Exenteration
- Total Exenteration

47. Palliative Therapy
• Pain relief with morphia(5-60mg) and
tramadol.
• Correction of vomiting and electrolyte
imbalance.
– Haloperidol 1.5-3mg
- Metoclopramide, Domperidone and steroids
• Diuretics and spironolactone for Ascites.
• Betadine douche or metronidazole irrigation
for vaginal discharge.

48. Prophylaxis
-HPV vaccines are available now, expensive.
-Given before the exposure to virus to
adolescent before sexual activity begun.
- confers 70% protection.