1. Management of
Abnormal PAP smear
Emad R. Sagr, MBBS, FRCSC

2. Impact of Cervical Cancer
• Morbidity
– Global prevalence: ~2.3 million
– Global incidence: ~500,000
– Globally, cervical cancer is second to breast cancer as
the leading cause of cancer in women.
• Mortality
– 3rd most common cause of overall female cancer-
related mortality worldwide
1. World Health Organization. Geneva, Switzerland: World Health Organization; 2003:1–74. 2. Ferlay J, Bray F, Pisani P, Parkin
DM. Lyon, France: IARC Press; 2004.

3. Facts and Figures
• The incidence has dramatically decreased from
– 32 cases per 100,000 in the 1940s to
– 8 cases per 100,000 in the 1990s.
• Mortality declined 45 % between 1970s and
1990s, while incidence declined 43.3 %

4. 59,929
29,814
Europe
78,896
61,670
Africa
48,328
21,402
South America
14,670
5796
United States/
Canada
1,063
330
Australia/
New Zealand
42,538
22,594
Southeast Asia
61,132
31,314
Eastern Asia
17,165
8124
Central America
157,759
86,708
Southcentral Asia
Cervical Cancer Incidence and Mortality Estimates by Region
1. Ferlay J, Bray F, Pisani P, Parkin DM. Lyon, France: IARC Press; 2004.

6. PAP TEST
• What is a Pap Smear ?
• The cervical transformation zone.
• All cervical intraepithelial neoplasias (CIN)
arise within the transformation zone of the
cervix.

7. PATIENT INSTRUCTION
• No intercourse during the 24 hours prior to the
test
• No douching during the 24 hours prior to the
test

8. Technique

9. Technique
• Visualize entire cervix if possible
• Carefully remove any obscuring discharge
• Sample ectocervix first with spatula
• Sample endocervix with gentle cytobrush
rotation
• Apply material uniformly to slide
• Fix rapidly with spray or liquid fixative

10. Technique
• Hold spray fixative 10 inches away from slide
• Collect cells before bimanual exam
• Avoid contamination with lubricant
• Test for GC and Chlamydia after pap smear

11. INFORMATION REQUIRED
• Patient name
• Patient age
• Last menstrual period
• History of hormone use
• IUD
• Previous abnormal Pap smears
• Relevant clinical information- e.g., abnormal
bleeding, discharge, pelvic pain, etc.

12. Specimen Interpretation
• Requires a well-trained and experienced
cytotechnologist
• Steps to reduce laboratory errors
– 10 % Rescreening.
– Limits in workload.

13. Advances in Specimen Collection and
Interpretation
• Fluid-Based (Monolayer) Technology
(ThinPrep and Autocyte PREP)
• Neural Networks
( PAPNET and the AutoPap 300 QC)
• HPV Genotyping
( Digene Hybrid Capture® HPV DNA Test )
• Optoelectronic screening
(Polarprobe)

14. Techniques of Cervical Cytology
• Liquid-based
• Conventional

15. Questions
• When should screening begin?
• What is the optimal frequency of cervical
cytology screening?
• At what age is it appropriate to recommend
discontinuing screening?

16. The 2001 Bethesda System
• More than 400 cytopathologists,
cytotechnologists, histopathologists, family
practitioners, gynecologists, public health
physicians, epidemiologists, and attorneys
participated in the workshop, which was
convened by the NCI.
• Cosponsored by 44 professional societies.
• More than 20 countries were represented.

17. THE 2001 BETHESDA SYSTEM
Terminology for Reporting Results of Cervical Cytology
• Specimen Adequacy
• General Categorization (Optional)
• Interpretation/Result
• Automated Review and Ancillary Testing
• Educational Notes and Suggestions (Optional)

18. SPECIMEN ADEQUACY
• Satisfactory for evaluation
– describe presence or absence of transformation zone
component and any other quality indicators, e.g., partially
obscuring blood, inflammation, etc.)
• Unsatisfactory for evaluation . . . (specify reason)
– Specimen rejected/not processed (specify reason)
– Specimen processed and examined, but unsatisfactory for
evaluation of epithelial abnormality because of (specify
reason……)

19. • GENERAL CATEGORIZATION (optional)
– Negative for Intraepithelial Lesion or Malignancy
– Epithelial Cell Abnormality: See Interpretation/Result (specify
squamous or glandular as appropriate)
– Other: See Interpretation/Result
• AUTOMATED REVIEW
– If case examined by automated device, specify device and result.
• ANCILLARY TESTING
– Provide a brief description of the test methods and report the result so
that it is easily understood by the clinician.

20. INTERPRETATION/RESULT
• Negative for Intraepithelial Lesion or Malignancy
– Organisms
• Trichomonas vaginalis
• Fungal organisms morphologically consistent with
Candida species
• Shift in flora suggestive of bacterial vaginosis
• Bacteria morphologically consistent with Actinomyces
species
• Cellular changes consistent with herpes simplex virus

21. INTERPRETATION/RESULT (Cont.)
• Negative for Intraepithelial Lesion or Malignancy
– Other non-neoplastic findings (Optional to report; list not
comprehensive)
• Reactive cellular changes associated with
– Inflammation
– Radiation
– Intrauterine contraceptive device
• Glandular cells status post hysterectomy
• Atrophy

22. INTERPRETATION/RESULT (Cont.)
• Epithelial Cell Abnormalities
– Squamous cell
• Atypical squamous cells (ASC)
– ASC-US
– ASC-H
• Low-grade squamous intraepithelial lesion (LSIL)
– Encompassing: human papillomavirus/mild dysplasia/cervical
intraepithelial neoplasia (CIN) 1
• High-grade squamous intraepithelial lesion (HSIL)
– Encompassing: moderate and severe dysplasia, carcinoma in
situ; CIN 2 and CIN 3
• Squamous cell carcinoma

23. INTERPRETATION/RESULT (Cont.)
– Glandular cell
• Atypical glandular cells (AGC) (specify endocervical,
endometrial, or not otherwise specified)
• Atypical glandular cells, favor neoplastic (specify
endocervical or not otherwise specified)
• Endocervical adenocarcinoma in situ (AIS)
• Adenocarcinoma
– Endocervical
– Endometrial
– Extrauterine
– Not otherwise specified (NOS)

24. THE WHO AND BETHESDA SYSTEM
TERMINOLOGY
WHO histological terms Bethesda Cytological Terms
CIN 1/ Mild Dysplasia LSIL
CIN 2 / Moderate Dysplasia HSIL
CIN 3 / Severe Dysplasia HSIL
CIN 3 / Carcinoma in Situ HSIL

25. Abnormal Pap test – How common is it?
12,200
cancers
300,000 HSIL
1.25 million LSIL
2-3 million ASC
50-60 million women screened

26. ASC frequency and association with
CIN
§ Least reproducible of cytological categories
§ Average frequency of ASC 4.4 %
§ ASC associated with CIN 2/3 5 - 17 %
§ ASC-H associated with CIN 2/3 24 - 94 %
§ ASC associated with cervical ca 0.1 - 0.2 %

27. Repeat Cytology
@ 6 mos X 2 HPV DNA Testing
Colposcopy
“When liquid-based cytology is used, or when co-collection for HPV DNA
testing can be done, "reflex" HPV DNA testing is the preferred approach”
ASCCP Management Guidelines ASC-US
Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ, for 2001 ASCCP-Sponsored Consensus
Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities.
JAMA. 2002;287:2120-2129.

28. Patient Management Using HPV Triage
ASCUS
HPV TEST
Low Risk + or HPV– HPV +
Repeat Pap and/or HPV
Test in 12 mo. or return to
routine screening at
discretion of clinician
COLPOSCOPY

29. Recommended Management of Women
with ASC-US
SPECIAL POPULATIONS
• Postmenopausal women with ASC-US should be
managed in the same manner as women in the general
population.
• Immunosuppressed women with ASC-US should be
managed in the same manner as women in the general
population.

30. Recommended Management of Women
with ASC-US
SPECIAL POPULATIONS
• Adolescent women (20 years and younger)
– Should not be screened unless they have been sexually active for 3
years
– With ASC-US, follow-up with annual cytological testing is
recommended.
– At the 24 month follow-up, those with an ASC-US or greater result
should be referred to colposcopy.

31. Recommended Management of Women
with ASC-US
SPECIAL POPULATIONS
• Pregnancy
Ø Mgt options (over age 20) same as nonpregnant,
with the exception that it is acceptable to defer
colposcopy until at least 6 weeks postpartum.

32. Recommended Management of Women
with ASC-H (CANNOT EXCLUDE HSIL)
All should have Colposcopy

33. Low-grade Squamous Intraepithelial
Lesion (LSIL)
• Cytological diagnosis of LSIL, 2% of women
• 2nd most common abnormal cytology report (ASC-US is most
common)
• 85% with LSIL, have biopsy-confirmed CIN
– 18% CIN II-III
– .03% invasive cervical cancer
• LSIL is highly predictive of HPV infection

34. Recommended Management of Women
with LSIL
All should have Colposcopy

35. High-grade Squamous Intraepithelial
Lesion (HSIL)
• 0.7 % of cytology reports
• 75% will have biopsy-confirmed CIN II-III
• 1-2 % invasive Cervical Ca
• An immediate Leep or Colposcopy/ECC is
acceptable (except in pregnancy or
adolescents)

36. Recommended Management of Women
with HSIL
All should have Colposcopy

37. Managing Women with HSIL
UNACCEPTABLE STRATEGIES
• Ablation is unacceptable in the following
circumstances:
Ø Colposcopy has not been performed
Ø CIN II-III is not identified histologically
Ø ECC identifies CIN of any grade
• Triage utilizing either of the following is
unacceptable
Ø Repeat cytology
Ø HPV DNA testing

38. AGC frequency and association with
CIN
• Mean frequency of AGC 0.4 %
• Associated CIN 1, 2, or 3 9 - 54 %
• AGC assoc. with AIS 8 %
• AGC assoc. with carcinoma 3 - 17 %
Jones and Davey Arch Pathol lab Med 2000,124:672
Jones and Novis. Arch Pathol Lab Med 2000;124:665
Ronnett et al, Hum Pathol 1999;30:816
Veljovich et al, Am J Obstet Gynceol 1998;179:382
Soofer and Sidaway Cancer 2000;90:207

39. Recommended Management of Women
with AGC
All should have
• Colposcopy
• ECC
• EMB

40. Conclusion
ASC-US
Repeat
Cytology HPV test Colposcopy
ASC-H LGSIL
HGSIL AGC
AIS SCC

41. And that s
the end of
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