1. HPV and Cervical Cancer Screening
Peter Valenzuela, MD, MBA, FAAFP
Assistant Dean for Clinical Affairs
Assistant Professor/Dept. of Family Medicine

2. Objectives Discuss key aspects of HPV including:
Types
Transmission
Course
Detection
Vaccine
Describe cervical cancer screening guidelines
Provide an introduction to colposcopy using cervical images

3. Background
Human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S.
Over half of sexually active men and women are infected with HPV at some point in their lives
6.2 million people in the U.S. become infected annually

4. Economic Impact
Approximately $3.5 billion spent on cervical HPV-related disease in the U.S. annually
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5. Types There are over 100 different types of HPV
Over 40 types infect mucosal surfaces of the ano-genital area
High risk (cancer-associated)-16,18,31,33,35,39,45,51,52,56,58,59,68,82
Low risk (non-oncogenic)- 6,11,40,42,43,44,54,61,72,73,81

6. Types High Risk Low Risk
HPV 16 most common (found in almost half of all cervical CA)
HPV 18 accounts for 10%-12% of cervical CA
Low Risk
HPV 6 & 11 most commonly found in genital warts

7. Transmission
Usually transmitted through direct skin-to-skin
Can occur from mother to baby in delivery
Detected on inanimate objects, but transmission via this route is unknown
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8. Risk Factors for HPV Infection
Young age (less than 25 years old)
Increasing number of sex partners
Early age at first intercourse (16 years old or younger)
Male partner has (or has had) multiple sex partners

9. Course Typical duration of new infection is 8 months
70% of women become HPV negative within 1 year
91% become HPV negative within 2 years
10% of women infected with HPV will develop persistent HPV infections
Even the majority of infections with high-risk HPV types generally clear within 2 years, failing to persist or progress to cervical cancer. This suggests that HPV infection alone is not sufficient for cervical cancer; rather, an interaction between high-risk HPV types and other host or environmental cofactors (e.g. smoking, oral contraceptive use) appears to play a role in disease progression
The peak prevalence of CIN 1 occurs at approximately 28 years of age, CIN 2/3 at 42 years of age, and cervical cancer at approximately 50 years of age. This suggests that there may be a sequenced evolution of stages for cervical cancer over time, beginning with infection with high-risk HPV types, viral persistence, and progression from CIN 1 through CIN 3, ultimately to invasive cervical cancer [Baseman & Koutsky, 2005]. However, some studies contradict the hypothesis that stages of HPV-related disease are sequential; for example, development of CIN 2/3 may occur in the absence of known previous CIN 1 [Schiffman, 2003].
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10. Detection HPV DNA test (Hybrid Capture II)
Can be analyzed from the residual fluid of a liquid-based cytology specimen
Detects high risk HPV types, but does not identify individual type
Indications for use
Routine adjunct to Pap in women 30 and over
Management of ASCUS

11. Prevention of HPV Quadrivalent HPV vaccine (Gardasil)
Protects against HPV 6,11,16,18
3 IM injections over six-month period ($360 for series)
Indicated in females 9-26 years old
Ideally before onset of sexual activity

12. Cervical Cancer Screening
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13. Cervical Dysplasia Classification
Bethesda System- developed by the CDC and NIH to standardize method
CIN Grading System
BETHESDA
CIN GRADING
ASCUS
Atypia
LGSIL
CIN I
HGSIL
CIN II
HGSIL Carcinoma In Situ
CIN III
Staging
Since the Pap smear was introduced in 1943, a number of methods have been developed to classify the results. The two methods commonly used today are the Bethesda System and the CIN Grading System.
The Bethesda System was developed by the CDC and NIH in order to have a comprehensive and standardized method of classifying Pap smear results. It uses the term squamous intraepithelial lesion (SIL) to describe abnormal changes in the cells on the surface of the cervix. Squamous refers to thin, flat cells that lie on the outer surface of the cervix. An intraepithelial lesion occurs when normal cells on the cervical surface are replaced by a layer of abnormal cells, and these changes are classified as high grade or low grade.
Bethesda System
ASCUS (atypical squamous cells of undetermined significance) - Borderline, some abnormal cells
LGSIL (low-grade squamous intraepithelial lesions) - Mild dysplasia and cellular changes associated with HPV
HGSIL (high-grade squamous intraepithelial lesions)- Moderate to severe dysplasia, precancerous lesions, and carcinoma in-situ (preinvasive cancer that involves only the surface cells)
Squamous cell carcinoma Cervical intraepithelial neoplasia (CIN) refers to new abnormal cell growth. Intraepithelial refers to the surface layers of the cells. The CIN System grades the degree of cell abnormality numerically, CIN I is the lowest and CIN III is the highest.
CIN Grading System Atypia - correlates with ASCUS CIN I - mild dysplasia and correlates with LGSIL CIN II - moderate dysplasia and correlates with HGSIL CIN III - severe dysplasia and correlates with HGSIL Carcinoma in-situ Cervical cancer

14. Management of an Abnormal Pap
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15. Management of an Abnormal Pap
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16. Colposcopy
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Indications:
Grossly visible or palpable abnormality of the cervix
Abnormal cervical cytology
Positive screening test for cervical neoplasia such as spectroscopy, cervicography, speculoscopy
Cervical cytology unsatisfactory due to unexplained inflammation
History of in-utero diethylstilbestrol (DES) exposure
Unexplained cervico-vaginal discharge
Unexplained abnormal lower genital tract bleeding
History of lower genital tract neoplasia (cervical, vaginal, vulvar)
Post-treatment surveillance
ASCCP

17. Colposcopy Ectopy Nabothian Cyst
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Ectopy-Most pronounced in adolescence and the first pregnancy when squamous metaplasia is most active.
It is also common with the use of oral contraceptives. It is an entirely normal finding, and does not warrant any kind of diagnostic or therapeutic response
Nabothian cysts: Single or multiple, the translucent cysts appear yellow and can be as large as several centimeters. Formation occurs secondary to blockage of mucin secreting endocervical crypts by overlying metaplastic squamous epithelium. Nabothian cysts are always located within the transformation zone. Prominent large vessels are often noted overlying the attenuated epithelial surface of the cyst. On close inspection, the vessels arborize normally and are not atypical (disorganized) in appearance. Nabothian cysts are normal. They do not require any treatment.

18. Colposcopy Leukoplakia
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Keratosis or leukoplakia: Lesions that appear white on visual inspection of the cervix prior to the application of acetic acid are termed keratosis or leukoplakia. Microscopy of these lesions reveals a thick hyperkeratotic or parakeratotic surface. Located within or outside of the transformation zone, keratotic lesions are raised and bright white. Leukoplakia is a nonspecific finding and may arise secondary to trauma such as with diaghram or pessary use, human papilloma virus infection or even invasive keratinizing squamous carcinoma. Biopsy is necessary to establish the exact diagnosis.
Coarse” vascular patterns (punctation, mosaicism, or both) characterized by:
Larger and varied caliber of vessels
Larger and variable intercapillary distances
“Umbilicated” mosaic patterns, with punctation in the middle of the “tiles” suggests CIN 3 / carcinoma-in-situ.
Vascular patterns can be striking and visible even at lower magnification
Vascular patterns change as acetic acid effects develop, then fade: keep watching!
Prominent and dilated vessels may blunt acetowhite change; Don’t miss the HSIL or invasive cancer because the examining eye is drawn to acetowhite change and away from the less-white HSIL or cancer!

19. Colposcopy Punctation
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Punctation- stippled appearance of capillaries appear as fine-to-coarse red spots after acetic acid

20. Colposcopy Mosaicism CIN I
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Mosaicism-linear, tile-like patterns, abnormal change made of small blood vessel appearing in linear form.

21. Colposcopy CIN II CIN III
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22. Colposcopy Strawberry Cervix
Common indicator of cervicitis
Trichomoniasis is usually the culprit
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Always keep in mind that cervicitis may make Pap interpretation more difficult and less accurate, and make colposcopic assessment more difficult. Cervicitis secondary to trichomoniasis results in coalescent erythematous patches giving a reverse punctation also called a “strawberry cervix”. The mucopurulent cervicitis of chlamydia and gonorrhea is associated with prominent vascularity and hypertrophy of the cervical ectropion. Many authorities recommend diagnostic tests and any indicated treatment before biopsy when any cervicitis (STD) or severe vaginitis is strongly suspected.

23. Summary Discuss key aspects of HPV including:
Types
Transmission
Course
Detection
Vaccine
Describe cervical cancer screening guidelines
Provide an introduction to colposcopy using cervical images

24. References
Centers for Disease control and Prevention
American Society for Colposcopy and Cervical Pathology
American College of Obstetricians and Gynecologists

25. References
Pfenninger and Fowler’s Procedures for Primary Care, 2nd Ed. 2003
Colposcopy and Treatment of Cervical Intraepithelial Neoplasia: A Beginner’s Mannual. Edited by Edited by J.W. Sellors and R. Sankaranarayanan
HPV Disease
Women’s Health Channel