Abnormal Pap and Cervical Dysplasia
BASICS
Description
- Cervical dysplasia: premalignant cervical disease also called cervical intraepithelial neoplasia (CIN); precancerous epithelial changes in the transformation zone of the cervix.
- Almost always associated with human papillomavirus (HPV) infections.
- CIN grading:
- CIN I: mild dysplasia, low-grade lesion, cellular changes limited to lower 1/3 of squamous epithelium.
- CIN II: moderate dysplasia, high-grade lesion, changes limited to lower 2/3 of squamous epithelium.
- CIN III (carcinoma in situ): severe dysplasia, high-grade lesion, full thickness involvement.
Systems Affected
- Reproductive system
Pediatric Considerations
- Cervical cancer before age 20 is rare (0.1%).
- Screening <21 years does not reduce cancer incidence or mortality compared to starting at 21.
Geriatric Considerations
- Stop screening >65 years if adequate prior screening and no CIN II+ in last 20 years.
- Adequate screening defined as:
- 3 consecutive negative cytology-only results or
- 2 consecutive negative HPV tests or
- Negative cotesting (cytology + HPV) within 10 years before stopping (most recent test within 5 years).
- Continue screening for β₯25 years post management of high-grade lesions even if past 65.
Pregnancy Considerations
- Lesions may progress during pregnancy but often regress postpartum.
- Colposcopy only to exclude invasive cancer in high-risk cases.
- Treatment contraindicated unless invasive cancer is suspected.
EPIDEMIOLOGY
- Cervical cancer is 4th most common cancer in women worldwide.
- In the US, incidence dropped to 20th in cancer deaths (2021).
- CIN III incidence peaks: 25-29 years.
- Invasive disease peaks: 15 years later.
- Most common in ages 35-44 years.
-
15% of cases occur in those >65 years (often due to lack of screening).
Incidence
- 2021 projection: 14,480 new cases; 4,290 deaths in US.
- Cervical cancer incidence has decreased >50% in last 40 years due to screening.
Prevalence
- High-grade dysplasia prevalence reduced significantly in HPV-immunized populations.
ETIOLOGY AND PATHOPHYSIOLOGY
- HPV is common; most sexually active people will get at least one type.
- High-risk HPV types: 16, 18, 31, 33, 35, 45, 52, 58.
- Types 16 and 18 cause ~70% of cervical cancers.
- Most HPV infections are transient; persistence leads to precancer risk.
- Women >30 years less likely to clear HPV.
- Low-risk HPV types: 6, 11, 42, 43, 44 cause genital warts and LSIL/CIN I.
RISK FACTORS
- HIV and immunosuppression
- In utero exposure to diethylstilbestrol
- Cigarette smoking
- Multiple sexual partners
- Associations: low socioeconomic status, high parity, oral contraceptives, poor nutrition
GENERAL PREVENTION
- Immunization:
- HPV vaccine decreases high-risk HPV infections and CIN2/3 pathology.
- Recommended for adolescents 11-12 years; can start as early as 9 years.
- Gardasil 9 FDA-approved for ages 9-26; shared decision-making for 27-45.
- Vaccine schedule:
- <15 years at first dose: 2 doses, 6β12 months apart.
- β₯15 years at first dose: 3 doses at 0, 2, and 6 months.
- Immunocompromised: 3 doses required.
- Safe sex and smoking cessation advised.
Screening Recommendations
| Age Group | Screening Method | Frequency | Notes |
|---|---|---|---|
| <21 years | No screening | β | USPSTF/ASCCP/ACOG recommendation |
| 21-29 years | Cytology only | Every 3 years | |
| β₯25 years | Primary HPV testing (preferred) or cytology | HPV every 5 years or cytology every 3 years | HPV assay must be FDA-approved for primary screening |
| 30-65 years | Primary HPV testing or cotesting (HPV + cytology) | Every 5 years | Cytology every 3 years acceptable if HPV testing unavailable |
| >65 years | Stop if adequate prior screening | β | Not high risk |
- Patients with hysterectomy and no history of CIN II+ should not be screened.
- HIV+ individuals: screen annually until 3 normal results, then every 3 years.
DIAGNOSIS
History
- Usually asymptomatic until invasive disease.
Physical Exam
- Pelvic exam may reveal external HPV lesions.
- Look for exophytic or ulcerative cervical lesions Β± bleeding.
Differential Diagnosis
- Acute/chronic cervicitis
- Cervical glandular hyperplasia
- Uterine malignancy
DIAGNOSTIC TESTS & INTERPRETATION
- No major difference in detecting cervical precursors between conventional and liquid-based cytology.
- Use cytobrush and extended tip spatula for adequate ecto- and endocervical sampling.
- Cotesting (HPV + cytology) sensitivity ~100%, specificity ~92.5%.
- High-risk HPV testing alone preferred for β₯25 years old.
- Cytology alone acceptable when HPV testing unavailable.
Bethesda 2014 Classification (Cytology)
- Squamous cell abnormalities:
- ASC-US: atypical squamous cells of undetermined significance
- ASC-H: cannot exclude high-grade lesion
- LSIL: mild dysplasia (CIN I)
- HSIL: moderate/severe dysplasia (CIN II/III, CIS)
- Glandular abnormalities:
- AGC: atypical glandular cells favor neoplasia
- AIS: adenocarcinoma in situ
- Adenocarcinoma
Clinical Action (ASCCP 2019 Guidelines)
- <25 years with ASC-US: HPV testing preferred.
- HPV positive: clinical action based on CIN 3+ risk.
- HPV negative: repeat cotesting at 3 years.
- ASC-H: colposcopy required.
- LSIL: colposcopy or repeat cotesting depending on HPV status.
- HSIL, CIN 2/3, AGC: colposcopy and/or treatment based on risk.
Test Interpretation
- Atypical squamous or columnar cells, koilocytosis hallmark of HPV infection.
TREATMENT
- Use ASCCP smartphone app for evidence-based algorithms (https://www.asccp.org/mobile-app).
General Measures
- Office evaluation, smoking cessation, safe sex, immunization.
Medical
- Treat infections/reactive Pap findings per organism.
- Condyloma acuminatum treatment per relevant guidelines.
Surgical/Procedural
- Expedited treatment recommended for nonpregnant patients β₯25 years with >60% immediate CIN 3+ risk.
- Observation preferred for CIN I.
- Excisional treatment preferred over ablative for HSIL and AIS.
- See "Cervical Malignancy" for cancer management.
ONGOING CARE
Follow-Up
- After treatment for HSIL, CIN II/III, or AIS, screen with HPV or cotesting every 3 years for at least 25 years.
PATIENT EDUCATION
- HPV vaccination, smoking cessation, protected intercourse, regular Pap screening.
PROGNOSIS
- CIN progression slow; regression common.
- Up to 43% CIN II and 32% CIN III regress.
- CIN III has ~30% risk of invasive cancer over 30 years; ~1% if treated.
- Early detected lesions have excellent treatment outcomes.
- 5-year survival for localized cervical cancer ~91.9%; overall 66.3%.
COMPLICATIONS
- Cervical stenosis
- Cervical incompetence β preterm labor
- Scarring affecting cervical dilation during labor
REFERENCES
- Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2020;24(2):102-131.
- Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: USPSTF recommendation statement. JAMA. 2018;320(7):674-686.
- Fontham ETH, Wolf AMD, Church TR, et al. Cervical cancer screening for average-risk individuals: 2020 ACS guideline update. CA Cancer J Clin. 2020;70(5):321-346.
- Massad LS, Einstein MH, Huh WK, et al. 2012 Updated consensus guidelines for management of abnormal cervical cancer screening tests. J Low Genit Tract Dis. 2013;17(5 Suppl 1):S1-S27.
Additional Reading
- ASCCP guidelines: https://www.asccp.org/management-guidelines
See Also
- Cervical Malignancy
- Condylomata Acuminata
- Trichomoniasis
- Vulvovaginitis, Prepubescent
Algorithms
- Pap, Normal and Abnormal in Nonpregnant Women Ages 25 Years and Older
- Pap, Normal and Abnormal in Women Ages 21-24 Years
Codes
| Code | Description |
|---|---|
| R87.619 | Unspecified abnormal cytological findings, cervix uteri |
| N87.9 | Dysplasia of cervix uteri, unspecified |
| N87.1 | Moderate cervical dysplasia |
Clinical Pearls
- HPV vaccine should be offered prior to sexual debut for maximum efficacy.
- Follow recognized screening guidelines to avoid over screening harms.
- HPV-only screening is more sensitive than cytology alone but assay availability may vary. ```