1. Colposcopy & the Evaluation of Abnormal PAPs
Dana Sprute, MD, MPH
UT Southwestern Austin Family Medicine Residency
Family Medicine Workshop
June 16, 2010

2. Objectives Review cervical cancer screening criteria.
Review Bethesda system of PAP description.
Review common PAP abnormalities.
Review role of HPV in evaluation of abnormal PAP
Understand the role of colposcopy in evaluation of abnormal PAP.
Understand the Reid’s Colposcopic Index & its use in colposcopic evaluation.
Be able to accurately describe colposcopic findings and determine presence & probable degree of cervical dysplasia.

4. Why Perform a PAP? Screening test for cervical cancer.
Early 20th century, cervical cancer was the most common cancer to affect women worldwide & in the U.S.
Cervical cancer is still the 2nd leading cause of cancer death in women worldwide.
Approximately 10,500 new cases occur annually in the U.S.; one third of these lead to death.
Approximately 45,000 cases of high-grade premalignant disease is detected annually through PAP screening and colposcopy evaluation.

5. Who Needs a PAP? US Preventive Services Task Force: AAFP:
“A recommendation”
Screen when (whichever comes first):
Within 3 years of onset of sexual activity
Age 21
AAFP:
strongly recommends at least every 3 years for women who have ever had sex and have a cervix.
ACOG: same as USPSTF
ACS: same as USPSTF

6. The 1991 Bethesda System Specimen Adequacy:
Satisfactory for evaluation
Satisfactory but limited by (scant cellularity, poor fixation, inflammation, blood, no endocervical component)
Unsatisfactory for evaluation (secondary to above).
General Categorization: (optional)
Within normal limits
Benign cellular changes
Epithelial cell abnormality
Benign Cellular Changes:
Infection: trich, fungal, coccobacilli (BV), HSV
Reactive changes: associated with inflammation, atrophy w/inflammation, radiation, IUD

7. The 1991 Bethesda System Epithelial Cell Abnormalities: Squamous cell:
Atypical squamous cells of undetermined significance (ASC-US)
Atypical squamous cells: cannot exclude high-grade lesion (ASC-H)
Low-grade squamous intraepithelial lesion (HPV mild dysplasia/CIN1)
High-grade squamous intraepithelial lesion (moderate/severe dysplasia, CIN2, CIN3, CIS)
Squamous cell carcinoma
Glandular cell:
Endometrial cells in postmenopausal women, cytologically benign
Atypical glandular cells of undetermined significance (AGUS)
Endocervical adenocarcinoma
Endometrial adenocarcinoma
Extauterine adenocarcinoma
Adenocarcinoma, NOS

8. Atypical Squamous Cells: Unknown Significance PAP Facts ASCCP Recommendations
Atypical Squamous Cells of Undetermined Significance (ASCUS) is the most common PAP abnormality.
In the U.S., 2 million ASCUS PAPs reported annually.
5% of all PAPs performed in the U.S. are reported as ASCUS.
5-10% of women with ASCUS PAP results have underlying high-grade squamous intraepithelial lesion (HGSIL).
30% of HGSIL lesions were initially reported as ASCUS by PAP exam.
Current recommendations for ASCUS PAP evaluation
HPV Test: High risk (-) repeat PAP 12 months; (+) colpo
Repeat cytology 6 & 12 months: (-) return to routine; (+) colpo
Colpo: No CIN/No HPV—PAP 12 months; CIN-I—PAP 6 months or HPV at 12 months.

9. Atypical Squamous Cells: cannot exclude High-grade lesion (ASC-H)
All require colposcopic exam (with ECC).
Colpo exam:
No CIN 2-3: PAP 6 & 12mon or HPV at 12mon
CIN 2-3: excisional biopsy
PAP Q6 months or HPV testing at 12 months.
HPV (-): return to routine screening
HPV (+) or > ASC: colposcopy

10. Low-grade Squamous Intraepithial Lesion (LSIL) PAP Facts ASCCP Recommendations
Most LSIL will revert to normal without therapy.
Up to 90% of LSIL will spontaneously regress (by 36 months).
15% of LSIL progress to HGSIL.
Progression associated with oncogenic HPV infection
Evaluation of LSIL:
Colposcopy (ECC preferred).
Satisfactory colpo & no lesion seen: PAP 6-12 months or HPV 12 months.
Satisfactory colpo & lesion seen:
No CIN: PAP 6-12 month or HPV 12 months
CIN 1: PAP 6-12mon or HPV 12 mon or PAP & colpo at 12 months
CIN 2-3: excision or ablation
PAP 4-6 months (3 negative=annual testing)
> ASC – colpo
HPV testing 6 months after treatment: (-) annual PAP; (+) colpo

11. High-grade Squamous Intraepithelial Lesion (HSIL) PAP Facts ASCCP Recommendations
98.9% of HGSIL PAPs have oncogenic HPV
3% of HGSIL PAP have invasive cancer
All HGSIL need:
Colpo, ECC
Satisfactory colpo:
No CIN/CIN 1: PAP & colpo Q6month (x 1yr)
Note: HPV serial testing has been taken out of the algorithm
CIN 2-3: excision
Unsatisfactory colpo:
No lesion: excision
CIN (any grade): per ASCCP guidelines

12. Atypical Glandular Cells Unknown Significance (AGUS)
Represent 0.1% of all PAPs annually
Association with adenocarcinoma (cervical, uterine, extrauterine/ovarian).
Initial Work-Up:
Colposcopy with endocervical sampling (ECC)
HPV testing
Endometrial sampling (EMB) if > 35yo or risk of endometrial neoplasia
Follow-Up:
Serial PAPs Q6M for 4 cycles (2 years)
HPV testing:
HPV negative: repeat PAP & HPV in 12mon
HPV positive: repeat PAP & HPV in 6 mon
PAP > ASC or HPV pos: colposcopy
Atypical Endometrial Cells:
Endometrial sampling: EMB
Endocervical sampling: ECC

13. Special Populations

14. Pregnant Women: Epidemiology of Cervical Cancer during Pregnancy (Source: ASCCP)
Rare, but most common cancer diagnosed during pregnancy.
2007 incidence of cervical cancer: 1 to 15 cases per 10,000 pregnancies.
Mean age of diagnosis is 34 years.
Increased incidence of invasive cervical cancer in pregnant women is suspected because women are delaying child-bearing later than ever in history.
These trends may make cervical cancer more common during pregnancy in the future.
The incidence of each stage at diagnosis is:
83% Stage I
10% Stage II
3% Stage III
2% Stage IV.
Stage for stage, the prognosis is similar to that of nonpregnant patients. It is fortunate that over 80% of these cases are Stage I at presentation.

15. Pregnant Women
Colposcopist should be experienced in cervical evaluation in pregnancy
Hormonal changes of pregnancy produce dramatic alterations in the colposcopic appearance of the cervix. Increased vascularity produces a cyanotic, bluish hue (Chadwicks sign).
Marked enlargement of the cervix cause increased vascularity, stromal edema, and stromal hypertrophy. Vaginal wall laxity and increased cervical mucus also may make visualization of the cervix more difficult.
Progressive eversion of the SCJ onto the ectocervix makes colposcopy satisfactory more often. Grading of lesions is more difficult than in the nonpregnant patient.
LGSIL lesion:
Colposcopy: if no CIN 2 or 3, postpartum follow-up
If CIN 2 or 3, per ASCCP Guideline (including biopsy of lesion)
Postpartum Reevaluation
Repeat colposcopy at least 6 weeks postpartum.
Disease progression during pregnancy is small.
Regression incidence approximately 12% to 70%.
Treatment, if indicated, should be based on the grade and location of disease identified postpartum.

16. Pregnancy

17. Adolescents (AKA Women < 20yo)
October 2007 change from previous guidelines (less aggressive management now).
ASC-US or LGSIL: PAP Q12M
> HGSIL:
Colpo:
No CIN 2-3:
observe w/ colpo & PAP Q6M (up to 2yrs)
2 consecutive negative PAP & no high grade colpo finding: routine screening (annual)
HSIL PAP persistent for 1yr: colpo with biopsy
CIN 2-3: biopsy & manage per ASCCP guideline

20. HPV Facts
90 % of preinvasive & invasive squamous neoplasms of the cervix have detectable HPV DNA.
High Carcinogenic Potential: 16,18,45,56
16 (CIN2-3=50%, LG/HG lesion=85%, Cancer=50%)
18,45,56 (CIN1=5%, Cancer=20%, aggressive course)
Risk Factors include:
Age at first intercourse
Number of sexual partners
Tobacco use (smokers have 50% higher risk of developing cervical cancer than nonsmokers)
Oral contraceptive pills
Immunosuppression (e.g. HIV)
Dietary factors (high fat diet, low Vitamin C or beta carotene intake)

21. HPV Facts Epidemiology Incidence: 25-30% annual infection rate
Prevalence: % of U.S. women have HPV (50% with oncogenic viral type)
Lifetime prevalence: 80% of U.S. women have had HPV by age 50.
HPV peak prevalence: years of age
HPV prevalence declines with age
HPV presence after age 40 is likely persistent and expressed (higher risk for dysplasia)
Most infection is latent or subclinical, and not clinically obvious (in women, most commonly diagnosed by abnormal PAP)
Worldwide, cervical cancer is the second most common malignancy in women (500,000 women affected annually). HPV is recognized as the primary cause of cervical cancer

22. New HPV Testing Guidelines: ASCCP Consensus Guideline 2009
At BFHC:
Age < 21: no PAP
Age 21-29: PAP w/ reflex HR HPV for ASCUS
Age > 30: HPV for all PAPs (q 3 yrs if negative).

23. HPV Vaccine Gardasil HPV viral types: 6, 11, 16, 18
3 vaccines: months 0, 2, 6

24. Colposcopy

26. A Little Colpo History Colposcopy means “to look into the vagina.”
First described by Hans Hinselman of Germany in 1925.
Hoped this would be an effective screening tool for cervical cancer (the most common malignancy of the era); clinically impractical and practice abandoned.
Early 1940s, George Papanicolaou develops cytologic screening test and PAP test becomes the cervical cancer screening test of choice.
Until early 1970’s, the evaluation of abnormal PAP was done by cervical cone biopsy; however, cone biopsy results demonstrated that most cytologic abnormalities were minor.
Colposcopy was developed as an intermediate step in evaluation of abnormal PAP tests and to determine who actually needed surgical intervention.

27. Colposcopy Skills: What defines competence
Colposcopic accuracy is defined as the clinical correlation between a colposcopic impression and the histologic report.
Skills needed to demonstrate proficiency (competence):
Visualization:
Locate the lesion
Assessment:
Assess the severity of the lesion
Sampling:
Determine the most severe lesion to biopsy
Correlation:
Correlate the colposcopic impression with the cytologic and histologic findings.

28. Informed Consent

31. Colposcopy Procedure in Brief
Colposcope used to identify area(s) of dysplasia.
Apply 3-5% acetic acid (vinegar) to highlight dysplastic
or koilocytotic areas.
Application of acetic acid coagulates proteins of the nucleus and cytoplasm and makes proteins opaque (acetowhite).
Doesn’t affect mature, glycogen-producing cells because there is less penetration.
Affects dysplastic cells due to larger amount of cytoplasm and larger nucleus; therefore, greater amount of protein and more acetowhite changes.
Apply Lugol’s solution.
Lugol negative areas indicate possible dysplasia

32. Colposcopy Evaluation in Brief
Satisfactory colpo:
Limits of lesion are seen.
Entire transformation zone is seen.
Colposcopic findings agree with histologic findings reported on the cervical biopsy.
If local treatment is planned:
Endocervical curettage must be negative.
Colpo findings should agree with pathology findings.
Unsatisfactory colpo: if above conditions not met.
If ECC is positive, local treatment (e.g. cryo) is contraindicated and patient should be referred for LEEP (loop electroexcision procedure) or conization.

33. Reid’s Colposcopic Index
RCI considers four characteristics of premalignant lesions:
Lesion margin
Color of acetowhitening
Vessels within the lesion
Iodine staining
Each category is assigned a value from 0-2
First three signs are evaluated after acetic acid application.
Fourth sign evaluated after application of iodine (Lugols solution)

34. 0 Points 1 Point 2 Points Margin Color Vessels Score Colpo Sign
Condyloma
Indistinct, feathered border
Jagged angular lesion
Satellite lesion (AW that extends beyond TZ)
Regular lesions with smooth, straight outlines
Sharp peripheral margins
Rolled, peeling edges
Internal borders between areas of differing appearance
Color
Shiny, snow-white
Indistinct AW, semitransparent rather than opaque
Shiny, off-white
Intermediate white
Dull, oyster gray
Vessels
Uniform, fine caliber
Randomly arranged with poorly formed patterns
Nondilated capillary loops
Absence of surface vessels following acetic acid soaking
Definite punctation or mosaicism.
Individual vessels dilated, arranged in sharply demarcated, well-defined patterns
Iodine Staining
Positive iodine uptake
Mahogany-brown color
Partial iodine uptake
Variegated, tortoise-shell appearance
Negative staining of lesion
Mustard yellow appearance
Score
0-2: HPV or CIN-I
Low grade disease
3-5: CIN- I or II
Intermediate grade dz
6-8: CIN-II or III
High grade disease

35. Colposcopy Clinical Impression
Normal
HPV Effect
CIN-I
CIN-II
CIN-III
CIS/Cancer
Based on:
Colposcopic Evaluation
Reids Colposcopic Index

38. Normal Cervix

39. Normal Cervix

40. Normal Cervix Squamous Metaplasia
Metaplasia is a normal transformation from one mature cell type (columnar) to a second mature type (squamous).
Metaplasia usuallly seen in the lower 1/3 of the EC.
Factors that cause metaplasia may include environmental conditions, mechanical irritation, chronic inflammation, pH changes or changes in sex steroid hormone balance.

41. Ectropion Eversion of the uterine cervix
Caused by columnar epithelium everting onto a portion of the cervix

42. Nabothian Cyst
Nabothian cysts form when the secretions from functional glandular epithelium become trapped below the surface of the skin.
This can occur because of:
normal deep infolding of the endocervical epithelium
when squamous exocervical epithelium covers over the mucous-producing endocervical epithelium (squamous metaplasia)
more commonly after childbirth and sometimes occurs concomitantly with cervicitis

43. Cervical Polyp Etiology is not well understood. Associated with:
inflammation of the cervix.
May result from an abnormal response to the female hormone estrogen.
Cervical polyps are relatively common, especially in women older than 20 who have had at least one child. They are rare in girls who have not started menstruating. There are two types of cervical polyps:
Ectocervical polyps develop from the outer surface layer cells of the cervix. They are more common in postmenopausal women.
Endocervical polyps develop from cervical glands inside the cervical canal. Most cervical polyps are endocervical polyps and are more common in premenopausal women.

44. Cervical Polyp
Polyps are usually cherry-red to reddish-purple or grayish-white.
Vary in size and often look like bulbs on thin stems.
Cervical polyps are usually not cancerous (benign) and can occur alone or in groups.
Most polyps are small, about 1 centimeter to 2 centimeters long.
Because rare types of cancerous conditions can look like polyps, all polyps should be removed and examined for signs of cancer.

45. HPV Natural History of HPV: Nonenveloped dsDNA virus
During intercourse, microabrasions in epithelial cells which allow HPV to invade and infect basal keratinocytes
High risk HPV integrate into host cell DNA which leads to dysregulation of cell growth.
Uncontrolled cell division leads to dysplasia
Normal transformation zone is the target of HPV
Not all HPV is destined to become dysplasia

47. Koilocytes: hyperchromatic nuclei, irregular nuclear border & sharply punched out perinuclear halos

49. HPV Lesions

50. Vaginitis

53. Trichomonas strawberry cervix

55. Acetowhite changes

58. Leukoplakia

59. Abnormal Vessels

60. Mosaicism

62. Erosion

63. Punctation

64. Cervical Cancer

65. Colposcopy Steps
Visual inspection of external genitalia, vaginal walls & cervix.
Application of Acetic Acid
Application of Lugol’s Solution
Cervical Biopsy & Endocervical Curettage
Hemostasis
Pressure
Monsel’s
Suture

66. Acetic Acid Application

67. Cervical Biopsy

68. Endocervical Curettage

69. Monsel’s Application

70. Case 0 16 yo healthy G0. Student at McCallum High School PAP: LGSIL
OCPs
What next?

71. Case 1 21 yo healthy G0. Student at UT Austin PAP: LGSIL OCPs
What next?

72. Case 1

73. Case 1: CIN-1
Reid’s Index
Colposcopy findings
Clinical Impression

74. Case 2 30 yo G0 Social Worker PAP: ASC-US (4/04) OCP
No HPV test performed d/t insufficient cellularity
OCP

75. Case 2

76. Case 2: CIN-2 Reid’s Index Colposcopy findings Clinical Impression
So What Happened?
Repeat PAP 8/04: ASCUS, HPV +
Colpo Impression: CIN-I w/HPV effect
Cx Bx: squamous metaplasia & reactive changes
Repeat PAP 2/05 : HGSIL (II-III)
Colpo Impression: CIN II w/ HPV effect.
Cx Bx: CIN I
Repeat PAP 1/06: LGSIL (“cells suspicious for HGL also present”); no HPV performed
Colpo Impression: CIN I
Cx Bx: CIN-I, “higher grade of dysplasia cannot be excluded”
LEEP Bx: HGSIL (II-III), margins clear
Follow-Up: Q6M PAP or HPV testing at 6-12 months, stop smoking. HPV neg: routine screening for 20 yrs; HPV pos: colpo w/ ECC

77. Case 3
27 yo G0
Insurance Auditor
PAP: ASC-H
Condoms

78. Case 3

79. Case 3: CIN-3 Reid’s Index Colposcopy findings Clinical Impression
So What Happened?:
Cx Bx: CIN II-III with HPV effect
LEEP Bx: Adenosquamous CIS, margins clear
Follow-Up: Q6M PAP, colpo, ECC; HPV testing at 12 months. Stop smoking, condoms
All PAP, HPV, ECC negative X2
Moved to Switzerland

80. Case 4 30 yo female G2P1011 State of Texas Auditor
Radiation exposure at Chernobyl 1986
PAP 2/01: Benign cellular changes; reactive cellular changes; satisfactory for evaluation.
PAP 4/02: HGSIL

81. Case 4

82. Case 4: CIS Reid’s Index Colposcopy findings Clinical Impression
So What Happened?:
PAP: HGSIL, severe dysplasia, CIN III
Colpo Impression: CIN-III
Cx Bx: Adenocarcinoma in situ
ECC: Adenocarinoma in situ
Referred to GYN-Onc
LEEP Bx (per GYN): Adenosquamous CIS, margins clear

83. Case 5
24 yo G0
Attorney
PAP: ASC-US
What next?

84. Case 5

85. Case 5: Normal Cervix Reid’s Index Colposcopy findings
Clinical Impression

86. Questions?

87. THANKS!! To Bryan Yeakley of Med Tech Associates of Central/South Texas for supplying the colposcopy equipment and models.

88. REFERENCES ASCCP Guidelines, 2009: HPV screening, www.asccp.org
ASCCP Guidelines,
Colposcopy Principles and Practice: An Integrated Textbook & Atlas. B. Apgar, G. Brotzman, M. Spitzer, Saunders 2002.
Screening for Cervical Cancer, U.S. Preventive Services Task Force, Release date: 1/2003.
Spitzer M, et al: Management of Histologic Abnormalities of the Cervix, AFP: Vol 73(1): , 1/1/2006.
Apgar B, et al: Management of Cervical Cytologic Abnormalities, AFP: Vol 70(10): , 11/15/2004
Brotzman GL: Evaluating the impact of HPV-related diseases. J Family Practice Special Edition: S3-9, July 2005.
Manos, et al: HPV Testing for Women with Equivocal Papanicolaou Test Findings, JAMA, 5/5/99: 281(17):
Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. NEJM, 1998; 338:
Ferris DG: Reid’s Colposcopic Index, J Fam Pract 1994; 39:65-70.
Ferris DG, et al: Colposcopic Accuracy in a Residency Training Program: Defining Competency & Proficiency, J Fam Pract 1993: 36(5):

89. Websites USPHSTF: www.ahcpr.gov/clinic/uspstf
American Society for Colposcopy & Cervical Pathology:
American Cancer Society:
American Academy of Family Physicians: