Description

• Cervical dysplasia: precancerous epithelial changes in the transformation zone of the uterine cervix and endocervical canal associated with persistent infection of high-risk human papillomavirus (HPV) types; potential precursor to invasive disease
• Cervical intraepithelial neoplasia or CIN encompasses a range of histologic findings. Biopsy material is typically obtained from colposcopy after an abnormal Pap smear result.
  • CIN I: mild dysplasia; low-grade lesion; cellular changes are limited to the lower 1/3 of the squamous epithelium.
  • CIN II: moderate dysplasia; high-grade lesion; cellular changes are limited to the lower 2/3 of the squamous epithelium.
  • CIN III or carcinoma in situ: severe dysplasia; high-grade lesion; cellular changes involve the full thickness of the squamous epithelium.
• System(s) affected: reproductive

Pediatric Considerations
Fewer than 0.1% of cervical cancers occur before age 21 years. Screening any asymptomatic individual with a cervix age <21 years is not recommended (1),(2).Geriatric Considerations

• Screening any immunocompetent individual with a cervix and age >65 years who has had adequate prior screening and no history of CIN II+ in the last 25 years is not recommended (3).
• Screening should continue beyond age 65 years per 2019 ASCCP Risk-Based Management Consensus Guidelines if there is risk for invasive disease (3),(4).

Pregnancy Considerations

• CIN diagnosed during pregnancy is most often stable or regresses postpartum, with regression rates reported between 39% and 69% in various cohorts (5).
• Colposcopy without endocervical sampling is recommended to exclude the presence of invasive cancer in high-risk individuals.
• Management is conservative, with treatment deferred until postpartum unless there is suspicion of invasive disease (6).

Epidemiology

Incidence of CIN III peaks between ages 25 and 29 years; invasive disease peaks 15 years later. Cervical cancer most commonly occurs in those aged 35 to 44 years. >15% of cervical cancer cases occur in those >65 years of age (occurs in those who did not get regular screening). Each year in the United States 14,000 new cases of cervical cancer are diagnosed, approximately 100,000 people are treated for cervical dysplasia, and 4,000 die of cervical cancer (3),(6).

Etiology and Pathophysiology

Transient HPV infection among sexually active individuals is very common.

• High-risk HPV types: 16, 18, 45, 31, 33, 35, 39, 51, 52, 56, 58, 59, and 68 together account for >95% of cervical cancer cases, although 16 and 18 account for 70% of cases (3) types for cervical cancer.
• Most HPV infections are transient, becoming undetectable within 1 to 2 years. Persistent infections are what place women at significant risk for developing precancerous lesions. Compared to younger women, women age >30 years are less likely to clear a new HPV infection.
• Low-risk types: HPV viral types 6, 11, 42, 43, and 44 are considered common low-risk types and may cause genital warts. HPV 6 and 11 (cause 90% of benign anogenital warts) can lead to low-grade squamous intraepithelial lesion (LSIL) and CIN I.

Risk Factors

• HIV infection and other immunosuppressive conditions
• In utero exposure to diethylstilbestrol
• Multiple sexual partners and partners with multiple partners
• Early age at first intercourse
• Lack of access to screening
• History of abnormal Pap smears, HPV infection, CIN, STI or a combination of these
• Increased risk associated with low socioeconomic status, tobacco use, high parity, oral contraceptive use (6)

General Prevention

Immunization: Immunization decreases high-risk HPV infections, CIN II/III cervical pathology, and invasive cervical cancer. Per the Advisory Committee on Immunization Practices (ACIP), offer HPV vaccine to adolescents 11 to 12 years of age and can start vaccination as early as 9 years old. Gardasil 9: The U.S. Food and Drug Administration (FDA) approved in October 2018 for use in females and males ages 9 to 26 years and via shared clinical decision for ages 27 to 45 years; 88% effective preventing dysplasia due to HPV types 16 and 18 (75% of cervical cancer), types 6 and 11 (anogenital warts), and protection against five additional HPV types, which cause approximately 25% of CIN II+ lesions. Current studies show maximum benefit from vaccination when administered before 14 years of age, prior to first sexual intercourse, and shared decision-making is recommended for vaccination of individuals ages 27 to 45 years because vaccination in this age group is not expected to be effective nor cost-effective of cancer prevention on a population level (3).

• Vaccine schedule: Only 2 doses are required when the first dose is given before 15 years of age, 6 to 12 months apart. 3 doses are recommended at interval of 0, 2, and 6 months when the first dose is given at ≥15 years of age.
• Immunocompromising conditions: 3 doses needed
• Safe sex practices: condom use; advise smoking cessation.
• Screening
  • Pap smear has been the main screening test for cervical cellular pathology, with or without cotesting for HPV.
  • Screening recommendations by age and source with follow-up for abnormal results: See algorithms “Cervical Cancer Screening (Pap): Normal and Abnormal in Women Ages 21–24 Years,” “Cervical Cancer Screening (Pap): Normal and Abnormal in Nonpregnant Women Ages 25–29 Years and Older,” “Cervical Cancer Screening (Pap): Normal and Abnormal in Average-risk, Nonpregnant Women Ages 30–65 Years” (1),(3) (USPSTF/ASCCP/ACOG).
  • Frequency of screening recommendation for average risk: USPSTF/ASCCP/ACOG generally agree by age and screen, but several guidelines are under revision in 2025. In general:
    • <21 years: Do not screen.
    • 21 to 29 years: Screen with cytology alone every 3 years American Cancer Society (ACS) primary HPV testing every 5 years starting at age 25 is preferred.
    • 30 to 65 years: “primary” HPV testing alone (with an FDA-approved assay for this purpose), HPV testing with cytology (cotesting) every 5 years or cytology alone every 3 years (3),(6)
    • >65 years who have had adequate prior screening, immunocompetent and average risk: Do not screen (1),(3).
  • 2020 ACS guidelines: recommends beginning screening at the age of 25 years and prefers primary HPV testing alone (2) if available; ages 21 to 24 years: no screening (3)
• Special circumstances: patients after hysterectomy with removal of the cervix and with no history of CIN II+ in past 25 years: Do not screen (1),(3).
• HIV-positive patients: Centers for Disease Control and Prevention (CDC) recommends to initiate screening with a Pap test within 1 year of sexual debut but no later than age 21, or at the time of HIV diagnosis if not previously screened; ages 21 to 29 years: screen annually until three consecutive negative test results, then every 3 years; age ≥30 years for life: annual Pap testing with HPV cotesting (preferred); if both cytology and HPV are negative, screening can be every 3 years.

History

Usually asymptomatic until there is invasive disease

Physical Exam

Exam with or with speculum occasionally may reveal external HPV lesions. Examine for exophytic or ulcerative cervical lesions, with or without bleeding.

Differential Diagnosis

Acute or chronic cervicitis secondary to infectious or noninfectious causes (e.g., peri- or postmenopause); cervical glandular hyperplasia; uterine malignancy

Diagnostic Tests & Interpretation

• ThinPrep is a liquid-based cytology method favored over conventional collection by reducing obscuring factors such as blood, inflammation, and poor fixation.
• Sample both the ectocervix and endocervix with cytobrush and spatula.
• Cervicovaginal primary HPV testing alone is >95% sensitive for detecting precancer, although sensitivity of cytology alone is 50–70%. In 2025, the only HPV tests approved by the FDA for primary HPV testing in cervical cancer screening are the Cobas HPV test (Roche Molecular Diagnostics) and the Onclarity HPV test (Becton Dickinson). These tests have a sensitivity for high-grade cervical abnormalities of 95–99%. The sensitivity and specificity of assays approved for HPV cotesting (HPV and cytology testing together) demonstrate a similar or slightly lower sensitivity, but specificity for high-grade lesions is lower than with primary HPV assays, resulting in somewhat more false positives.
• Cytology: Bethesda 2014 system (cytologic grading) of epithelial cell abnormalities: Report specimen Adequacy and general categorization; adequacy (amount of cellular material), presence or absence of endocervical cells, and specimen type (conventional or liquid based); categorization negative for intraepithelial lesion or malignancy (NILM) versus epithelial cell abnormality:
  • Squamous cell abnormalities:
    • Atypical squamous cells (ASCs) (of undetermined significance [ASC-US]; ASCs cannot exclude high-grade squamous intraepithelial lesion or HSIL [ASC-H])
    • Low-grade squamous intraepithelial lesion (LSIL): encompasses HPV/mild dysplasia/CIN I
• HSIL: encompasses moderate/severe dysplasia, carcinoma in situ, CIN II and CIN III
• Glandular cell abnormalities:
  • Atypical glandular cells (AGCs): favor neoplasia, or not otherwise specified
  • AGCs: AIS adenocarcinoma in situ (AIS), adenocarcinoma

General Measures

Office evaluation and observation; promote smoking cessation; promote safe sex ectocervix practices; promote immunization.

Medication

Infective/reactive Pap smear: Treat organism/condition found on Pap smear results. Condyloma acuminatum treatment options: See chapter “Condylomata Acuminata.”

Surgery/Other Procedures

• Expedited treatment that bypasses colposcopy biopsy is recommended for nonpregnant patients ≥25 years of age with immediate CIN III+ risk of >60% and is acceptable for immediate CIN III+ risk between 25% and 60%, although stressing the importance of shared decision-making (4).
• Observation is preferred to treatment for CIN I (4). Colposcopy can be deferred for certain patients and repeat HPV testing or cotesting in 1 year is recommended if immediate CIN III+ risk is low (<4%).
• Excisional treatment (e.g., loop electroexcision, LEEP) is preferred to ablative treatment for histologic HSIL (CIN 2 or CIN 3). For AIS, excision is recommended (4).
• If cervical malignancy, see “Cervical Malignancy.”

Follow-up Recommendations

After successful treatment (excision or ablation) and initial posttreatment management, individuals should reenter screening with HPV testing or cotesting at 3-year intervals for at least 25 years (4).

Patient Education

HPV vaccination, smoking cessation, protected intercourse, regular screening with Pap smear per guidelines

Prognosis

• Progression of CIN to invasive cervical cancer is slow, and the likelihood of regression is high: Up to 43% of CIN II and 32% of CIN III lesions may regress. CIN III has a 30% probability of becoming invasive cancer over a 30-year period, although only about 1% if treated. Lesions discovered early are amenable to treatment with excellent results and few recurrences.
• The 5-year survival rate for cervical cancer patients is 66.3%. The 5-year relative survival rate for patients diagnosed with localized disease is 91.9%.

Complications

Aggressive cervical surgery may be associated with cervical stenosis, cervical incompetence (leading to preterm labor), and scarring affecting cervical dilatation in labor.

Additional Reading

American Society for Colposcopy and Cervical Pathology. ASCCP diagnostic and management guidelines. https://www.asccp.org/management–guidelines. Accessed September 8, 2025.

See Also

• Cervical Malignancy; Condylomata Acuminata; Trichomoniasis; Vulvovaginitis, Prepubescent
• Algorithms: Cervical Cancer Screening (Pap): Normal and Abnormal in Nonpregnant Women Ages 25–29 Years and Older; Cervical Cancer Screening (Pap): Normal and Abnormal in Women Ages 21–24 Years; Cervical Cancer Screening (Pap): Normal and Abnormal in Average-risk, Nonpregnant Women Ages 30–65 Years

ICD-10

• R87.619 Unspecified abnormal cytological findings in specimens from cervix uteri
• N87.9 Dysplasia of cervix uteri, unspecified
• N87.1 Moderate cervical dysplasia
• N87.0 Mild cervical dysplasia
• D06.9 Carcinoma in situ of cervix, unspecified

SNOMED

• 439888000 abnormal cervical Papanicolaou smear (finding)
• 73391008 dysplasia of cervix (disorder)
• 285836003 Cervical intraepithelial neoplasia grade 1 (disorder)
• 285838002 Cervical intraepithelial neoplasia grade 2 (disorder)
• 92564006 Carcinoma in situ of uterine cervix (disorder)