Cervical Dysplasia

Description of Medical Condition

Pre-invasive neoplastic epithelial changes in the transformation zone of the uterine cervix often associated with human papilloma virus infections

Mild dysplasia (CIN I or SIL low grade) — cellular changes are limited to the lower one-third of the squamous epithelium
Moderate dysplasia (CIN II or SIL high grade) — cellular changes are limited to the lower two-thirds of the squamous epithelium
Severe dysplasia (CIN III or SIL high grade or carcinoma in situ) — cellular changes involves the full thickness of the squamous epithelium

System(s) affected: Reproductive

Genetics: N/A

Incidence/Prevalence in USA: Difficult to assess due to wide variability in false negative Papsmear reporting and uneven distribution of qualified colposcopy practitioners. Prevalence 3,600/100,000 at age 27-28.

Predominant age: The median age for carcinoma in situ is 28 years. Earlier lesions can be expected at younger ages

Predominant sex: Female only

Medical Symptoms and Signs of Disease

Frequently none
Occasionally associated with condyloma acuminata in the vulva, vagina, or anus
Occasionally there are co-existing sexually transmitted diseases in the lower reproductive tract, e.g. chlamydia, gonorrhea

What Causes Disease?

Strong linkage with infections by human papilloma viruses types 16,18, 31, 33, and 35. Other types of the same virus have also been implicated.

Risk Factors

Multiparity and pregnancy before age 20 years
Multiple sexual partners
Early age in first sexual intercourse
Condyloma acuminatum infection elsewhere in the body
Cigarette smoking
Prostitution
Lower socioeconomic status

Diagnosis of Disease

Differential Diagnosis

Invasive carcinoma of the cervix
Condyloma acuminatum

Laboratory

Pap smear

Drugs that may alter lab results:

Surgical lubricants e.g., K-Y Jelly

Disorders that may alter lab results: N/A

Pathological Findings

Clumping of the nuclear chromatin material
Reversal of the nuclear/cytoplasmic ratio
Koilocytosis
Hyperchromasia

Special Tests

Viral DNA hybridization (Virapap) and others
Colposcopy
PAPNET system to review negative Pap smears
CYTYC 2000 thin prep Pap test (replacement of current Pap preparations)

Diagnostic Procedures

Papanicolaou smear
Colposcopy and directed cervical biopsies
Cone biopsy (by cold knife, laser, or loop excision)
Endocervical curettage
Loop electrosurgical excision procedure (LEEP)
Cervicography
Speculum examination
Use of HPV DNA typing to select certain cases with borderline abnormalities, e.g., atypical squamous cells of undetermined significance (ASCUS), for closer fol-lowup and colposcopy

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient

General Measures

Office evaluation and observation

Surgical Measures

Outpatient surgery — cryotherapy, laser ablative or excisional cone, cold knife cone, electrosurgical loop excision of transformation zone

Activity

Four weeks of pelvic rest after cone biopsy

Diet

No restriction

Patient Education

See Followup section

Medications (Drugs, Medicines)

Drug(s) of Choice

Treatment is primarily surgical
Fluorouracil (Efudex) once or twice daily as 5% vaginal cream supplemental therapy

Contraindications: Hypersensitivity to 5-fluorouracil

Precautions:

If hand is used in application of 5-fluorouracil, wash hand immediately afterwards
Avoid contact of 5-fluorouracil with eyes, nose, or mouth

Significant possible interactions: N/A

Alternative Drugs

N/A

Patient Monitoring

Repeat Pap smears every 4 months during the first year after cone excision for severe dysplasia, every 6 months thereafter. For lesser lesions, repeat Pap smear yearly. Probe endocervical canal to assure patency.

Prevention / Avoidance

Monogamy of both sexual partners
Use of condom during coitus if unable to practice monogamy
Abstain from smoking
Emphasize importance of yearly Pap smears for patients
Ability to obtain skilled colposcopy service as needed
Patient education (individually or by community services) to emphasize the need for Pap smear
Educate medical care providers to make patient referrals for the screening service unless they provide it themselves

Possible Complications

Some severe dysplasia will progress to invasive carcinoma of the cervix
Possible complications following cone biopsy of the cervix:
- Hemorrhage
- Infection
- Cervical stenosis
- Cervical incompetence
- Infertility
- Incomplete excision of dysplastic tissue
- Recurrence

Expected Course / Prognosis

Generally excellent
Persistence of dysplasia can occur due to incomplete excision
Recurrence of dysplasia can occur due to inability to eradicate the human papilloma virus in the patient’s body or prevent new infections

Miscellaneous

Associated Conditions

Condyloma acuminatum
Carcinoma of the cervix

Age-Related Factors

Pediatric: Very rare

Geriatric: Less frequent

Others: This is usually a problem for the women in the reproductive age group. The median age is 28 years for severe dysplasia. For lesser lesions, the median ages tend to be much lower.

Pregnancy

Dysplasia may progress during pregnancy
It is important to determine the severity of dysplasia and to exclude the presence of invasive carcinoma during pregnancy
Dysplasia does not require definitive treatment during pregnancy
Dysplasia by itself is not an indication for cesarean section

International Classification of Diseases

622.1 Dysplasia of cervix (uteri)

Other Notes

Squamous intraepithelial lesion (SIL) is in reference to Pap smear only

Abbreviations

CIN = cervical intraepithelial neoplasia SIL = squamous intraepithelial lesion