4. Every 7Minutes,
1 Indian woman dies of Cervical Cancer
Disease Burden
Infact India is a Capital for Cervical Cancer
5. IF YOU CAN PREVENT IT
CANCER
You Don’t Need To Cure
6. Herold Zur Hausen
The Nobel Prize Winner, Medicine 2008
HPV is the necessary or the key cause of cervical
cancer
Cervical cancer does not and will not develop in
the absence of the persistent
presence of HPV DNA.
7. HPV 16
HPV 18
HPV 6
HPV 11
Cancer causing Types1,2,4 Non-cancer causing types1,2
>75% of Cervical Cancer5,6
>50% of Vaginal & Vulvar Cancer5
90% of Anogenital warts5
HPV is a necessary cause of cervical cancer – 99.7%4
HPV
1.Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 2. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 3. Muñoz N, Bosch FX, Castellsagué X, et al. Int J
Cancer. 2004;111:278–285. Reprinted from J Virol. 1994;68:4503–4505 with permission from the American Society for Microbiology Journals Department. 4. Walboomers JM, Jacobs MV, Manos MM, et al. J
Pathol. 1999;189:12–19. 5. X. Castellsagué, S. de Sanjose, T. Aguado, K. S. Louie, L. Bruni, J.Muñoz, M. Diaz, K. Irwin, M. Gacic, O. Beauvais, G. Albero, E. Ferrer, S. Byrne,F. X. Bosch. HPV and Cervical
Cancer in the World. 2007 Report. WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Available at: www.who.int/hpvcentre6. Bhatla N et al.Vaccine (2008;26; 2811-17
Human Papillomavirus (HPV)
8. Ca Cervix
Slow Growing Cancer
Many opportunities for detection &treatment
of Precancerous lesions
9. • CERVICAL mucosa goes
through the SERIES OF
CHANGES before
developing into full blown
carcinoma
• SCREENING in such
cases becomes a viable
option to catch disease
young.
Normal mucosa
Dysplasia
Low grade intraepithelial
lesion
High grade intraepithelial
lesion
10. Natural History of Cervical Cancer
HPV
infection
CIN 1
CIN 2,3
HPV
disappearance
Invasive CA
Avg. 10-13 yrs
Avg. 6-
24 mo
Avg. 6-
12 mo.
12. DISEASE PROGRESSION
Invasive
cervical cancer
Time YearsMonths
Normal
epithelium
HPV infection;
koilocytosis
CIN I CIN II CIN III
CIN I 57% CIN II 43% CIN III 32%
Approx. likelihood of regression
Borderline Mild Moderate Severe Dyskaryosis
16. Universal Screening- Why?
• In many DEVELOPED COUNTRIES, a SUCCESS
STORY of decline in the incidence of and mortality
caused by cervical cancer has been observed in the
past 30 years as a result of screening by cytology.
• Cervical cancer has PRECURSOR, low and high
grade intraepithelial lesion, which have EFFECTIVE
TREATMENTS available.
• Screening also gives an opportunity for educating
women who are constantly at high risk.
17. Type of screening
• Conventional cytology
• Liquid-based monolayer cytology
• Human papillomavirus testing
• Testing in resource-poor areas
18. Widespread
introduction of
the Pap begins
Conventional Pap smear LBC
1949 1996 2000’s
HPV testing
Vaccine
Cervical cancer prevention:
Evolution !!
Markers
19. A tribute to Dr.GeorgeA tribute to Dr.George
PapanicolaouPapanicolaou
20. After introduction in 1928 as new cancer diagnosis,
After 1943 PAP smear became a routine
USA
Mortality Due to Cancer
Cervix
1940
2000
14/100,000
women
4/100,000
women
Screening programmes successful in all developed countries
Screens only cervical cancer
21. Cervical cytology
GOLD STANDARD IN CERVICAL
CANCER SCREENING.
• Eight cross sectional studies from different
developing countries show SENSITIVITY ranging
from 28.9% to 76.9%.
• Recent reviews the mean SENSITIVITY and
SPECIFICITY of cytology was 75% and 94%
respectively.
American Journal of epidemiology,1995
Obstetrics and Gynaecology, 1998
Annals of intrnal Medicine, 2000
23. Comparison of HPV DNA to Pap
N Eng J Med, 2007: Canadian Cervical Cancer Screening
Trial (CCCaST)
94.6%
55.4%
94.1%
96.8%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Sensitivity HPV
DNA
Sensitivity Pap Specificity HPV
DNA
Specificity Pap
Missed CIN2+
N Eng J Med 2007; 357: 1,579 - 88
95% CI: 84.2-100 95% CI: 33.6–77.2
P=0.01
95% CI: 96.3-97.3
P<0.001
95% CI: 93.4-94.8
24. Why ca cervix prevention not given
importance by Govt. in India?
IT IS NOT
25. Cervical Cancer Screening In India
• There are No Organized Screening Programs available
in India
• Cytology based screening programmes are difficult
to organize because:
1. Lack of political will
2. Limited infrastructure
3. Few trained personnel
4. Lack of funds
27. In India,
Universal Vaccination
can haveSubstantial effect in
reducing the morbidity of cervical
cancer in,where an organization
screening program may not exist
for all women in near future.
Villa LL. Vaccine. 2006; 24 (suppl 1) : S2# - 8
GOI – has NO MONEY for
universal vaccination
28. The Recently Launched National Program for
Prevention & Control of Cancer, Diabetes,
Cardiovascular Diseases & Stroke (NPCDCS,
Ministry of Health & FW, Government of India)
has among its major objectives
cervical cancer control through opportunistic
screening of women above 30 years.
29. Kudos to FOGSI members
• ↓ MMR – we are close to realise MDG -5
• Big Challenge of 2013 - ↓ Cancer
Cervix Rate in India
30. •1940-1989: annual “pap smear” for all women
-Linkage of “annual pap smear” to “annual health exam”
•1987: Walton Commission (British Columbia)
-Cytology screening every 3 years
•1989: AMA, ACOG, AMWA Consensus Statement
-Annually, starting at sexual activity or 18 years old
-After 3 negative smears, testing may be done less frequently
-Longer intervals based on the absence of risk factors
Evolution of Cervical Cancer
Screening / Intervals
32. 1. American Cancer Society (ACS)
2.American Society for Colposcopy and Cervical
Pathology (ASCCP),
3. American Society for Clinical Pathology (ASCP)
4. U.S. Preventive Services Task Force (USPSTF)
5. American College of Obstetricians and Gynecologists
(ACOG)
Endorsed by
33. FOCUS Of
Cervical Cancer Screening
Guidelines 2013
• When to start screening
• Screening method and intervals
• When to stop screening
• Screening after Hysterectomy
• Pelvic exams
• Screening among women who have been
vaccinated against human papillomavirus (HPV)
34. Current Recommendation 2013
• Apply to women who have a cervix,
regardless of sexual history.
• Do not apply to women who have received a
diagnosis of a
- high – grade precancerous cervical lesion or
- Cervical cancer.
- Who are immunocompromised
(such as those, who are HIV positive)
36. SHOULD NOT BE SCREENED REGARDLESS
OF THE AGE OF SEXUAL INITIATION OR
OTHER RISK FACTORS.
(STRONG RECOMMENDATION)
Age 21.
Women aged <21 years
37. •Most HPV infections are transient
•When HPV infection persists, transit to cancer is quite long
•Spontaneous regression of low grade lesions is common
•Invasive cervical cancer is very rare in 15-19 year olds
-14 cervical cancers annually
-1-2 cases per 1 million women
•In teens, screening does not reduce mortality
-Cervical cancer rates have not changed since 1973-
1977, before practice of screening at 18 or first intercourse
Why Start Cervical Cytology at 21?
ACOG Practice Bulletin No. 109, Dec 2009
38. Screening method and intervals
21 to 65 Years
• Cytology 21-29 years of age EVERY 3 YEARS.
(conventional or 30-65 years of age
liquid based)
Strong recommendation
Second Recommendation
39. Statement about annual screening
FOR SCREEN NEGATIVE
If Screening Negative
Repeat after 3 years
Women of any age should not be screened annually
by any screening method.
(Strong recommendation)
However , they should come for annual check-up
40. HPV + Cytology Co-Testing: Benefits
• Compared to cytology alone, improved accuracy and
earlier diagnosis of CIN 2+
• High negative predictive value important in women
unable or unwilling to have every 3 year screening
• While each co-test is more expensive, longer intervals
and very high NPV could reduce overall costs
41. HPV co-testing SHOULD NOT
BE USED for women
aged <30 years.
HPV Co -Test
(cytology + HPV test administered together)
21-29 years of age
42. 30 – 65 years of age
• If Screen Negative
Every 5 years
(Strong recommendation)
• THIS IS THE PREFERRED METHOD
• (Weak recommendation).
HPV co-test
(cytology + HPV test administered together)
43. Atypical Squamous Cells of Undetermined
Significance (ASC-US)
• Most common cytological abnormality
• Option 1 : repeat Cytology in 12 months
-If Negative-Cytology in 3 years
-If ASC or greater-Colposcopy
• Option 2 : Preferred: Reflex HPV Testing
-If Positive: colposcopy
-If Negative: Repeat Co-testing in 3 years
44. HPV Positive, Cytology Negative
Occurs in 11% of women aged 30 to 34 years;
2.6% of women aged 60 to 65 years
• Option 1: repeat co-testing in 12 months
-If HPV-positive or ASC-US+: colposcopy
-If HPV-negative or Cytology negative: rescreen with co-
testing in 3 years
• Option 2: reflex test for HPV16 or HPV16/18 genotypes
-If HPV16 or HPV 16/18 positive: colposcopy
-If HPV16 or HPV 16/18 negative: co-test in 12 months
• Do not immediately colposcope HPV positive/cyto negatives
45. Proposed Algorithm for the
Management of Women ≥30
HPV Negative HPV Positive
Repeat both
tests at 5
years
HPV 16 - / 18 –
Other HR HPV
+
HPV 16 + and /
or HPV 18 +
ColposcopyRepeat both
tests at 1 year
Cytology
Negative
+ HPV
Testing
46. Annual cervical cancer screening
should NOT be performed. (Level A evidence)
Patients should be counseled that
annual well-woman visits are recommended
even if cervical cancer screening is not
performed at each visit.
HPV Co- Test
Screen Negative
inwomen aged 30–65 years
47. Primary HPV testing (alone)
For
Screening
screening by HPV testing alone is not
recommended in most clinical settings.
(Weak recommendation)
48. When to Stop Screening
• Stop at age 65 for women with adequate
negative prior screening, no CIN2+ within the
last 20y.
Definition of adequate negative screening:
• 3 consecutive negative Paps or
• 2 consecutive negative HPV tests
49. Rationale for stopping at 65 years
• CIN2+ is rare after age 65
– Most abnormal screens, even HPV+, are false +
and do not reflect precancer
• HPV risk remains 5-10%
• Incident HPV infection unlikely to lead to
cancer within remaining lifetime
Chen HC et al. JNCI 2011;103:1387-96;
Rodrigues AC et al. JNCI 2009;101:721-8
50. When NOT to stop at age 65 years
If history of CIN2, CIN3, or AIS
– Continue “routine screening” for at least 20
years, “even if this extends screening past age
65.”
51. When to stop screening - 2
• Stop after HYSTERECTOMY with
removal of cervix and no history of
CIN2+
• “Evidence of adequate negative
prior screening is not required”
52. Rationale for stopping after
Hysterectomy
• Vag cancer rate is 7/million/year
• 663 vag cuff Paps needed to find one VAIN
• 2,066 women followed after hyst. for average 89 months
– 3% had VAIN, 0 had cancer
• Risk of Pap abnormality after hyst = 1%.
Pearce KF et al. NEJM 1996;335:1559-62;
Piscitelli JT et al. AJOG 1995;173:424-30
53. Women who have had a SUPRA-CERVICAL
HYSTERECTOMY (cervix intact) should
continue screening
according to Age guidelines.
(Strong recommendation)
SCREENING IN
POST – HYSTERECTOMY CASE
54. Women at any age with a history
of HPV Vaccination should be
screened according to the age
specific recommendations for the
general population.
Screening among those immunized
against HPV 16/18
5th Recommendation
55. SCREENING A VACCINATED COHORT
• Vaccination against HPV 16/18
– Reduces CIN3+ by 17-33%
– Reduces colposcopy by 10%
– Reduces treatment by 25%
• “ Recommended screening practices
should not change on the basis of HPV
vaccination.”
Paavonen J et al. Lancet 2009;374:301-14
56. The need for a BIMANUAL PELVIC EXAM
in subsequent yearly check-ups
<21 – No need
21 - shared decision
58. AGE SCREENING
< 21 No Screening
21-29 Cytology alone every 3 years
30-65 Acceptable: Cytology alone every 3 years*
Preferred ??: Cytology + HPV every 5 years* OR
> 65 No screening, following 3 consequetive neg prior
screens in last decade
After total hysterectomy No screening, if no history of CIN2+ in the past 20
years of cervical cancer ever
HIV-positive
-Immunosuppressed (e.g., Annually
2013 Guidelines : ACS, ASCCP,
American Society for Clinical Pathology
CA Cancer J CLIN March 2012
• 1st
time that all 3 organizations involved with cervical cancer prevention and the
USPSTF have endorsed equivalent guidelines
59. How to prepare for your pap test
- Not to schedule during periods.
- If you are going to have a pap testing in the next two days
• You should not douche (rinse the vagina with water or another fluid).
• You should not use a tampon
• You should not use a birth control foam, cream or jelly
• You should not use a medicine or cream in your vagina
60. Summary
1. 27% of the world burden of Cervical Cancer is seen in India.
2. Screening is recommended in women of >21yrs 2013
3. No screening required before 21 yrs
4. Screening should stop at 65 yrs and after hysterectomy
“The biggest gain in reducing cervical cancer incidence and mortality
would be achieved by increasing screening rates among women rarely
or never screened. . .
Clinicians, hospitals, health planners, and public health officials should
seek to identify and screen these women.”
ACS, 20002
He first reported that uterine cancer could be diagnosed by means of a vaginal smear in 1928, but the importance of his work was not recognized until the publication, together with Herbert Traut, of Diagnosis of Uterine Cancer by the Vaginal Smear in 1943. The book discusses the preparation of vaginal and cervical smears, physiologic cytologic changes during the menstrual cycle , the effects of various pathological conditions, and the changes seen in the presence of cancer of the cervix and of the endometrium of the uterus. He thus became known for his invention of the Papanicolaou test, commonly known as the Pap smear or Pap test, which is used worldwide for the detection and prevention of cervical cancer and other cytologic diseases of the female reproductive system. In 1961 he moved to Miami, Florida, to develop the Papanicolaou Cancer Research Institute at the University of Miami, but died in 1962 prior to its opening. Papanicolaou was the recipient of the Albert Lasker Award for Clinical Medical Research in 1950. [3] Papanikolaou's portrait appeared on the obverse of the Greek 10,000-drachma banknote of 1995-2001, [4] prior to its replacement by the Euro. In 1978 his work was honored by the U.S. Postal Service with a 13-cent stamp for early cancer detection.
