1. Cervical Disease and Neoplasms
Maria Horvat, MD, FACOG

2. Cervical Disease – Risk factors
HPV
Smoking – 2 fold increase
Young age at 1st coitus
Multiple sexual partners
A partner with multiple sexual partners
High parity
Lower socioeconomic status
Young age at 1st pregnancy

3. HPV in the United States

4. Cervical Disease HPV associated with 99.7% of all cervical cancer
HPV types associated with higher oncogenic risk:
16, 18
31, 33, 35 45
51, 56

5. HPV – high risk types

6. HPV Obligatory intra-nuclear virus Most remit spontaneously
5% of infected women have persistent infection

7. PAP test
Only a screening test
Goal:
To prevent cervical cancer

8. Histology of (SIL) squamous intraepithelial lesions.
Grade 1 = CIN 1; Grade 2 = CIN 2; Grade 3 = CIN 3

9. Cervical Neoplasia

10. Potential Co-Factors in Cervical Carcinogenesis
Other infectious agents
Herpes
Chlamydia
HIV and other immunosuppression
Diet
Smoking
Hormonal contraceptives
Weak immunomodulatory effect
Eversion of columnar epithelium
Decrease in blood folate levels
Progesterone effect on HPV

11. Management of Adolescent Women (<18 yrs) with histological diagnosis of CIN – Grade 1
< 18 yrs old with CIN 1
Repeat Cytology at 12 mos
< HSIL > HSIL
Negative > ASC Colposcopy
Routine Screening

12. Management of Adolescent women (<18 yrs) with histological diagnosis of CIN – grade 2,3
<18 yrs old with CIN 2,3
Either treatment or observation is acceptable, provided colposcopy is satisfactory.
When CIN 2 is specified, observation is preferred. When CIN 3 is specified, or colposcopy is unsatisfactory, treatment is recommended.
Observation OR Treatment
With colposcopy and cytology with excision or
at 6 mos intervals for 24 mos ablation of T-zone
2x negative cytology colposcopy worsens or
And normal colpo High-grade cytology or
colpo. Persists for 1 yr.
Routine Screening Repeat Biopsy CIN 3, or CIN 2 that persists
Recommended for 24 mos since initial dx

13. Coloposcopic Examination
Management of Women with Atypical Squamous Cells: Cannot exclude high grade SIL (ASC – H)
>20 yrs old with ASC-H
Coloposcopic Examination

14. >20 yrs old with ASC-US
Management of Women with Atypical Squamous cells of undetermined significance - ASC-US
>20 yrs old with ASC-US
Repeat Cytology HPV DNA testing
@ 4-6 mos
Negative >ASC Positive Negative
(for high risk type)
Repeat
@ 4-6 mos Colposcopy Repeat cytol.
@ 12 mos

15. Naming

16. Cervical Intraepithelial Neoplasia
Biopsy Result
Regress
Persist
Progress to CIS
Progress to invasion
CIN 1
57%
32%
11% 1%
CIN 2
43%
35%
22% 5%
CIN 3
<56%
-----
>12%

17. Acetowhite Epithelium
Colposcopic Grading
Low Grade
High Grade
Acetowhite Epithelium
Shiny or snow white, semitransparent
Dull, oyster white
Surface
Flat
Flat or irregular contour
Demarcation
Diffuse, irregular, flocculated, feathered
Internal demarcation line absent
Sharp, straight line
Internal demarcation line may be present
Vessels
Fine, with regular shapes, uniform caliber, normal aborization pattern
Punctation or mosaicism associated with coarse, dilated vessels with increased intercapillary distance; bizarre vessels without aborization, commas, hockey sticks, corkscrews, sharp bends
Iodine
Yellow, or variegated brown
Mustard yellow, yellow or iodine negative

18. Summary for the non-gynecologist
ASCUS
Negative HPV type Positive
Repeat Pap Refer for
in 6 mos coloposcopy

19. CIN 1 – mild dysplasia < 18 yrs old >18 yrs old
Repeat Pap Colposcopy

20. CIN 2,3
Colposcopy

21. Confirmed CIN 2,3 Excision
(adolescents may perform colposcopy q 6 mos up to 24 mos)

22. Interventional Techniques - Excisional
Conization
Cone of tissue is excised for further examination and/or to remove a lesion
Tissue is usually stained with iodine to demarcate the area of resection
Cold knife
Laser
LEEP
Loop electrosurgical excision procedure
May be complicated by burn artifacts
Ablative
Cryotherapy
Use of a probe containing carbon dioxide or nitrous oxide to freeze the entire transformation zone and area or the lesion
Laser vaporization therapy

23. Atypical Glandular Cells
AGUS
Colposcopy
ECC
Endometrial Sample, women >35 yrs

24. What is colposcopy?

25. Cervical Cancer – staging review
Stage 0: CIS, CIN grade III
Stage 1: carcinoma strictly confined to the cervix
Stage 2: cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina
Stage 3: carcinoma has extended to the pelvic wall. On rectal exam there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower 1/3 of the vagina. All cases with hydronephrosis or non-functioning kidney unless known to be due to other causes.
Stage 4: Carcinoma has extended beyond the true pelvis, or has involved the mucosa of the bladder or rectum.

26. Cervical Cancer Staging
Stage 0: The cancer cells are very superficial (only affecting the surface) are found only in the layer of cells lining the cervix, and they have not grown into (invaded) deeper tissues of the cervix. This stage is also called carcinoma in situ (CIS) or cervical intraepithelial neoplasis (CIN) grade III.

27. Cervical Cancer Staging
Stage I: In this stage the cancer has invaded the cervix, but it has not spread anywhere else.
Stage IA: This is the earliest form of stage I. There is a very small amount of cancer, and it can be seen only under a microscope.
Stage IA1: The area of invasion is less than 3 mm (about 1/8-inch) deep and less than 7 mm (about 1/4-inch) wide.
Stage IA2: The area of invasion is between 3 mm and 5 mm (about 1/5-inch) deep and less than 7 mm (about 1/4-inch) wide.
Stage IB: This stage includes Stage I cancers that can be seen without a microscope. This stage also includes cancers that can only be seen with a microscope if they have spread deeper than 5 mm (about 1/5 inch) into connective tissue of the cervix or are wider than 7 mm.
Stage IB1: The cancer can be seen but it is not larger than 4 cm (about 1 3/5 inches).
Stage IB2: The cancer can be seen and is larger than 4 cm

28. Cervical Cancer Staging
Stage II: In this stage, the cancer has grown beyond the cervix and uterus, but hasn't spread to the walls of the pelvis or the lower part of the vagina.
Stage IIA: The cancer has not spread into the tissues next to the cervix (called the parametria). The cancer may have grown into the upper part of the vagina.
Stage IIB: The cancer has spread into the tissues next to the cervix

29. Cervical Cancer Staging
Stage III: The cancer has spread to the lower part of the vagina or the pelvic wall. The cancer may be blocking the ureters (tubes that carry urine from the kidneys to the bladder).
Stage IIIA: The cancer has spread to the lower third of the vagina but not to the pelvic wall.
Stage IIIB: The cancer has grown into the pelvic wall. If the tumor has blocked the ureters (a condition called hydronephrosis) it is also a stage IIIB.

30. Cervical Cancer Staging
Stage IV: This is the most advanced stage of cervical cancer. The cancer has spread to nearby organs or other parts of the body.
Stage IVA: The cancer has spread to the bladder or rectum, which are organs close to the cervix.
Stage IVB: The cancer has spread to distant organs beyond the pelvic area, such as the lungs.

31. Question #1.
What if HGSIL pap and normal colposcopy?

32. Answer #1.
LEEP or cone biopsy.

33. Question #2.
Biopsy on face cervix is normal and ECC is positive, what is the next step?

34. Answer #2.
LEEP or cone biopsy.

35. There is hope!
Gardisil immunization guards against types 6, 11, 16, and 18.
Administer at 0, 2, and 6 months for females 9 years or older.

36. HPV Vaccine Trials

37. Phase 2 Trial of Quadrivalent HPV Vaccine: Conclusions
The vaccine was highly effective in reducing incidence of persistent HPV infection
Efficacy with regard to clinical disease associated with HPV types 6,11,16,18, was 100%
The vaccine was highly immunogenic, inducing high antibody titers to each HPV type
The vaccine was generally well tolerated

38. Do condoms help prevent?
YES!
60% decrease in transmission
Does not eliminate risk.

39. Pap smear schedules:
Many different recommendations
ACOG
APGO
ACS

40. Pap smear recommendations
1st pap by age 21 or within 3 years of 1st coitus
Annually until the age of 30
Pap with HPV at age 30, then can perform every few years.

41. Pap smear recommendations:
Post Menopausal
Some guidelines: No Pap
ACOG: q 3-5 years
Hysterectomized female:
If hysterectomy for benign reasons, then pap q 3-5 years
Yearly if:
Cervix present
History of abnormal paps
History of gyne cancer
History of DES exposure
History of cervical cancer
Smoking (increases chance of vaginal cancer)

42. References
APGO Educational Series on Women’s Health Issues: Advances in the Screening, Diagnosis, and Treatment of Cervical Disease
Review in Obstetrics and Gynecology, Vol. 1 No
American Society for Colposcopy and Cervical Pathology
Crosstalk; Preventing Cervical Cancer and Other Human Papillomavirus-related diseases