Cervical cancer develops in a woman's cervix (the entrance to the uterus from the vagina). Almost all cervical cancer cases (99%) are linked to infection with high-risk human papillomaviruses (HPV), an extremely common virus transmitted through sexual contact. Although most infections with HPV resolve spontaneously and cause no symptoms, persistent infection can cause cervical cancer in women. Cervical cancer is the fourth most common cancer in women. In 2018, an estimated 570 000 women were diagnosed with cervical cancer worldwide and about 311 000 women died from the disease. Effective primary (HPV vaccination) and secondary prevention approaches (screening for, and treating precancerous lesions) will prevent most cervical cancer cases. When diagnosed, cervical cancer is one of the most successfully treatable forms of cancer, as long as it is detected early and managed effectively. Cancers diagnosed in late stages can also be controlled with appropriate treatment and palliative care. With a comprehensive approach to prevent, screen and treat, cervical cancer can be eliminated as a public health problem within a generation.

1. CERVICAL CANCER
DR ALKA MUKHERJEE
DR APURVA MUKHERJEE
NAGPUR M.S.INDIA

2. • Cancer of the uterine cervix is the second most common
cancer among women world-wide.
• It is also the second most common cancer among Indian
women, which constitute the largest burden of cervical
cancer patients in the world.
• One out of every five women in the world suffering from this
disease is an Indian.
• Besides the high incidence of cervical cancer, owing to its
late diagnosis and with consequent poor survival, 25% of
global mortality due to cervical cancer occurs in India.
INTRODUCTION

3. • The establishment of a strong link between high-risk
persistent human papillomavirus (HPV) infections and the
occurrence of cervical cancer has resulted in the recent
development of HPV related control strategies for the
prevention of cervical cancer.
• These include interventions ranging from prophylactic HPV
vaccines to various screening approaches.
• The latter include visual inspection with acetic acid or lugol‘s
iodine (VIA/VILI), Papanicolaou test (Pap test or Pap smear)
and HPV DNA testing.

4. • Several screening based prevention programs have been
initiated in developed countries.
• Pap cytology test or HPV DNA - primary method of
screening.
• The annual incidence and mortality from cervical cancer has
come down by 50-70% since the introduction of regular
population based screening.
• Evidence suggests that screening is important from
macroeconomic point of view as well.
• Global investment in cervical cancer prevention could save
up to an economic value of USD 1 trillion, both due to gain in
disease free life years as well as with reduction in treatment
expenditure.

5. • Cervical cancer is a preventable disease as it has a well
defined, long pre-malignant phase which can be detected by
regular screening tests and follow up.
• Unfortunately, most women in India are not aware about
the screening.
• More women in India die from cervical cancer than in any
other country.
• New cases of cervical cancer detected in India: 96,922 every
year
• Deaths due to cervical cancer in India: 60,078/year

6. Who are at risk?
• Persistent infection of the cervix with Human Papillomavirus
(HPV)
• Having many sexual partners
• Husband having multiple sexual partners
• Having first sexual intercourse at a young age
• Giving birth to many children
• Smoking
• Having other diseases which lower immunity such as
HIV/AIDS, immunosuppressive drugs, transplant etc.

7. Can it be prevented?
• (I) Primary Prevention: It is designed to prevent the disease
from occurring in the first place.
• Adopt safe sex practices (avoid multiple sexual partners).
• Use of male condoms as barrier contraceptives to reduce the
risk of HPV infection.
• Timely treatment of reproductive tract infections.
• There is evidence that circumcision for men may reduce the
incidence of infection among sexual partners.

8. (II) Secondary Prevention:
• Secondary prevention aims at detecting the disease in its
early stages (pre-cancers) through screening and to prevent
its progression.
• Screening tests are done in apparently healthy women to
diagnose changes in the cervix which are pre-cancerous and
could develop into cervical cancer in future.
• If the abnormal tissue or cells are removed, the disease can
be prevented from progressing to cancer.
• Available screening tests for cervical cancer include Pap
smear test, VIA (visual inspection with acetic acid), VILI
(visual inspection with Lugol’s iodine) and HPV DNA test.

9. The Pap smear is a simple test to collect a small sample of cells from the
cervix which helps to diagnose precancerous and cancerous conditions of
the cervix. It also aids in diagnosing infections and inflammation of the
lower reproductive tract.
• Who should get the Pap test done?
• As per the International recommendations, the age of
screening is 21 years. In our country due to low resources
for screening, national recommendations are to start
screening at 30 years of age.
• Women who are 30 years and above should undergo a
Pap test once in every 3 years until the age of 65 years. If
this test is combined with HPV test, then the duration of
screening can be increased to 5 years.
• Women who do not routinely require Pap test
• Women aged below 21 years and above 65 years
• Women who have undergone hysterectomy for benign
condition

10. WHEN SHOULD THE PAP TEST BE DONE?
• The Pap test, yields optimum results, if scheduled between
10 to 20 days of the menstrual cycle. The woman should not
be menstruating at the time of test.
• Preparation for Pap smear
• Following should be avoided 48 hours before the test:
1. Intercourse
2. Douching of vagina
3. Vaginal medications
4. Vaginal contraceptives like creams/ jellies

11. Results of Pap test
A Pap test result may be reported as normal or
abnormal.
• Normal Pap test
• If the test report is normal, this means no abnormal or cancerous
cells have been found in the smear taken.
• Abnormal Pap tests
• Abnormal Pap test results usually do not mean that the woman
has cancer.
• Most often there is a small problem with the cervix.
• If results of the Pap test are unclear or show a mild abnormality in
the cells of the cervix, repeat the Pap test in 6 weeks, in 6 months
or a year, or run more tests.
• Treating abnormal cells that don’t go away on their own can
prevent almost all cases of cervical cancer.
• If the test findings suggest more severe abnormality in the cells, it
is confirmed by further procedures – colposcopy & biosy

12. How can it be diagnosed?
• If any of the screening tests (Pap test, VIA, HPV test) are
found to be positive, further testing may be necessary to
determine whether the changes in cervix are cancerous
• Colposcopy: A procedure in which a colposcope (a lighted,
magnifying instrument) is used to check the vagina and
cervix for abnormal areas.
• Biopsy: A sample of tissue is cut from the cervix and viewed
under a microscope by a pathologist to check for signs of
cancer. A biopsy that removes only a small amount of tissue
(punch biopsy) is usually done in the OPD.

13. WHAT ARE DANGER SIGNALS?
• Abnormal vaginal bleeding: Bleeding and spotting between
periods, unusually longer or heavier periods, bleeding
after menopause
• Unusual or excessive vaginal discharge with foul smell
• Vaginal bleeding after having sexual intercourse
• Pain in the lower abdomen or pelvic pain
• Pain during sexual intercourse

14. Challenges specific to the type of screening test
A. VIA:
a) Recommended as it is a low-cost point-of care diagnostic test.
b) But VIA based program needs training of healthcare provider /
ANMs, continuous monitoring of quality and reliable quality
assurance control, all of which require adequate resources in
terms of manpower training.
c) Require basic infrastructure such as an examination table,
lighting, Cusco‘s speculum, gloves, swabs and acetic acid.
d) VIA test also needs to be repeated every 3 years.
e) Test sensitivity is on par or better than cytology but specificity
is lesser than cytology.

15. B. Cytology:
a) Takes around two weeks to make the result of screening test available -
loss of follow up can be high
b) Training needs to be imparted to ANMs (Auxiliary Nurse and Midwives)
and LHVs (Lady Health Visitors) for sample collection.
c) Along with other laboratory instruments/ consumables which are usually
available in the hospital supplies, specific instruments (e.g., CERVEX brush)
for sample collection will be required.
d) specific reagents will be required for microscopic examination of the
samples.
e) Cytopathology labs in Indian public health sector are mostly located at
tertiary care centres and in urban areas in the private sector.
f) Training of pathologists in pap smear reporting is essential to get sufficient
sensitivity / specificity.
g) Liquid based cytology (LBC) may be considered to increase accuracy and
reduce unsatisfactory smears; cost per test is very high.

16. C. HPV DNA:
a) Specific consumables will be required for sample collection
(e.g., Digene Cervical Sampler) - costly.
b) Specimen Transport Medium (STM) to transport the
collected sample to laboratory -expensive.
c) Sample needs to be carried in ice- box and stored at the
temperature of -20 degree Celsius.
d) Specific equipment is required for examination of sample
(e.g., Hybrid Capture- II assay) - expensive.
e) takes around two weeks to make the result of screening
test available - loss of follow up can be high.

17. • HPV DNA and cytology based Pap smear - high sensitivity
and specificity respectively but are costly and resource
intensive in the form of requirement of specialist/trained
manpower and laboratory set up.
• Visual inspection with acetic acid or lugol‘s iodine -
moderate sensitivity and specificity - relatively less
expensive and low resource requiring - Affordable and
effective methods in screening women. (Government of
India, under the aegis of National Program for Prevention
and Control of Cancer, Diabetes, Cardiovascular Diseases and
Stroke (NPCDCS)
• Screening of cervical cancer - using VIA for women between
age group of 30-65 years for every 5 years.

18. Markov model

19. Process indicators related to target population in cervical cancer screening

20. HPV vaccination:
• Prophylactic vaccines for cervical cancer target HPV 16 and 18, the most
common oncogenic types of HPV responsible for cervical cancer.
• HPV vaccination is not effective against all oncogenic HPV types.
• Currently two vaccines, licensed globally are available in India;
• a quadrivalent vaccine (against HPV genotypes 6, 11, 16, 18) and
• a bivalent vaccine (against HPV genotypes 16, 18).
• The vaccine dose is 0.5 ml given intramuscularly, either in the deltoid
muscle or in the antero-lateral thigh.
• It is available as a sterile suspension for injection in a single-dose vial or
a prefilled syringe.
• The recommended age for initiation of vaccination is 9–14 years. Catch-
up vaccination is permitted up to the age of 26 years.
• Females who have not been exposed to the HPV infection are likely to
benefit more from the vaccine.

21. • Indian Academy of Pediatrics (IAP) recommendations on
HPV vaccination:
• Only 2 doses of either of the two HPV vaccines for girls aged
9-14 years: doses at interval of 6 months
• For girls 15 years and older, and those with HIV/AIDS on
chemotherapy or after organ transplant: dose at 0, 1-2 and 6
months.

22. PLEASE NOTE:
• Vaccine does not guarantee complete protection against
cervical cancer. Cervical screening is still important.
• Research is ongoing to look into the duration of protection
on that vaccine provides
• Duration of protection of vaccine: currently unclear.
Research is ongoing to look into.
• VACCINATION IS NOT A REPLACEMENT FOR CERVICAL
CANCER SCREENING
• Currently, there are no guidelines on HPV vaccination in
India.

23. Treatment of pre-cancerous lesions may include the following:
Removal or destruction of the part of the cervix affected by
disease
• Invasive: three types of treatment procedures are used to
treat cervical cancer
A. Surgery,
B. Radiotherapy and
C. Chemotherapy.
• These therapies may be given alone or in combination with
one another.
• Treatment depends on the stage of the cancer, the type of
tumor cells and a woman’s medical condition.

24. • Cryosurgery: Application of freezing probe to destroy
abnormal or diseased tissue in the cervix for about 5
minutes.

25. Loop electrosurgical excision procedure (LEEP): Procedure to
remove abnormal and or cancerous cells in the cervix using a
thin, low-voltage electrified wire loop that acts as a knife.

26. Laser surgery: Using a laser beam to burn the abnormal
cells in the cervix.
Conization: Excision of a cone-shaped sample of tissue from
the mucous membrane of the cervix by using cold knife
or scalpel. This procedure requires hospital admission.

27. • Hysterectomy: for women whose tumor
cannot be completely removed by conization
and who no longer want to have children.

28. • The process to find out the spread of disease is called staging.
• Stage 0 or Carcinoma in situ: abnormal cells are found in the
innermost lining of the cervix which may not be seen to naked
eye.
• Stage I: In this stage, cancer is limited to cervix only.
• Stage II: Cancer has spread beyond the cervix but not to
the tissues that line the part of the body between the pelvic
wall or to the lower third of the vagina.
• Stage III: Cancer has spread to the lower third of the vagina,
and/or to the pelvic wall, and/or has caused kidney problems.
• Stage IV: Cancer has spread to the bladder, rectum, or other
parts of the body.

29. • Stage I:The carcinoma is strictly confined to the cervix uteri
(extension to the corpus should be disregarded)
• IA Invasive carcinoma that can be diagnosed only by microscopy,
with maximum depth of invasion <5 mm
– ○IA1 Measured stromal invasion <3 mm in depth
– ○IA2 Measured stromal invasion ≥3 mm and <5 mm in depth
• IB Invasive carcinoma with measured deepest invasion ≥5 mm
(greater than stage IA), lesion limited to the cervix uteri
– ○IB1 Invasive carcinoma ≥5 mm depth of stromal invasion and <2 cm
in greatest dimension
– ○IB2 Invasive carcinoma ≥2 cm and <4 cm in greatest dimension
– ○IB3 Invasive carcinoma ≥4 cm in greatest dimension

30. • Stage II:
• The carcinoma invades beyond the uterus, but has not
extended onto the lower third of the vagina or to the pelvic
wall
• IIA Involvement limited to the upper two‐thirds of the
vagina without parametrial involvement
– ○IIA1 Invasive carcinoma <4 cm in greatest dimension
– ○IIA2 Invasive carcinoma ≥4 cm in greatest dimension
• IIB With parametrial involvement but not up to the pelvic
wall

31. • Stage III:
• The carcinoma involves the lower third of the vagina and/or
extends to the pelvic wall and/or causes hydronephrosis or
non‐functioning kidney and/or involves pelvic and/or paraaortic
lymph nodes
• IIIA Carcinoma involves the lower third of the vagina, with no
extension to the pelvic wall
• IIIB Extension to the pelvic wall and/or hydronephrosis or
non‐functioning kidney (unless known to be due to another cause)
• IIIC Involvement of pelvic and/or paraaortic lymph nodes,
irrespective of tumor size and extent (with r and p notations)
– ○IIIC1 Pelvic lymph node metastasis only
– ○IIIC2 Paraaortic lymph node metastasis

32. • Stage IV:
• The carcinoma has extended beyond the true pelvis or has
involved (biopsy proven) the mucosa of the bladder or
rectum. A bullous edema, as such, does not permit a case to
be allotted to stage IV
• IVA Spread of the growth to adjacent organs
• IVB Spread to distant organs

33. WORKUP
• History and physical (H&P)
• Complete blood count (CBC) (including platelets)
• Cervical biopsy, pathologic review
• Cone biopsy as indicated
• Liver function test (LFT)/renal function studies
• Imagingc
• Smoking cessation and counseling intervention if indicated
• Consider HIV testing
• Consider examination under anesthesia (EUA)
• Cystoscopy/proctoscopye (≥ stage IB2)
• Consider options for fertility sparing

35. TREATMENT OF INVASIVE CANCER
• Stage I Cervical Cancer
• Treatment of stage I cervical cancer may include surgery,
chemotherapy and/or radiation therapy depending on the sub-
stage, age and desire of the patient and preference of the treating
physician.
• Total hysterectomy with or without bilateral salpingo-
oophorectomy
• Modified radical hysterectomy and removal of lymph nodes.
• Internal radiation therapy.
• Radical hysterectomy and removal of lymph nodes.
• Radical hysterectomy and removal of lymph nodes followed by
radiation therapy plus chemotherapy.
• Radiation therapy plus chemotherapy.
• A combination of internal radiation therapy and external radiation
therapy

37. • Stage IA1 no lymphovascular space invasion (LVSI) - Cone biopsy with negative
margins (preferably a non-fragmented specimen with 3-mm negative margins)
• (If positive margins, repeat cone biopsy or perform trachelectomy)
• Stage IA1 with LVSI and Stage IA2 - Cone biopsy with negative margins
(preferably a non-fragmented specimen with 3-mm negative margins)
• (if positive margins, repeat cone biopsy or perform trachelectomy) + pelvic lymph
node dissection (consider sentinel lymph node [SLN] mapping) or
• Radical trachelectomy + pelvic lymph node dissection (consider SLN mapping)
• Stage IB1 - Cone biopsyi with negative margins (preferably a non-fragmented
specimen with 3-mm negative marginsj)
• (If positive margins, repeat cone biopsy or perform trachelectomy)
• Cone biopsy with negative marginsj (preferably a non-fragmented specimen with
3-mm negative margins)
• (if positive margins, repeat cone biopsy or perform trachelectomy) + pelvic lymph
node dissection (consider sentinel lymph node [SLN] mapping)k or Radical
trachelectomy + pelvic lymph node dissectionk (consider SLN mapping)
• Radical trachelectomy + pelvic lymph node dissectionk ± para-aortic lymph node
dissection (consider SLN mapping)

38. • Stage II Cervical Cancer
• Treatment of stage II cervical cancer may include either of
the following:
• Radical hysterectomy and removal of lymph nodes followed
by radiation therapy plus chemotherapy.
• A combination of internal radiation therapy and external
radiation therapy plus chemotherapy.
• Radical hysterectomy and removal of lymph nodes.
• Radical hysterectomy and removal of lymph nodes followed
by radiation therapy plus chemotherapy.

39. • Stage III Cervical Cancer
• Treatment of stage III cervical cancer may
include internal and external radiation therapy combined
with chemotherapy
• Stage IV Cervical Cancer
• Radiation therapy to relieve symptoms caused by the cancer
and improves quality of life (radiation therapy as palliative
therapy).
• Chemotherapy and targeted therapy (monoclonal
antibodies). Chemotherapy as palliative therapy to relieve
symptoms caused by the cancer and improve quality of life.