Cervical Cancer Screening

Aka: Cervical Cancer Screening, Pap Smear Intervals, ASCCP Calculated Risk Based Protocol, Primary Cervical HPV Testing Protocol

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II. Precautions

  1. Up to 15-20% of U.S. Cervical Cancer is due to adenocarcinoma (not associated with HPV infection in 25% of cases)
  2. Up to 25% of U.S. women eligible for screening are underscreened
    1. Nearly 50% of new Cervical Cancer cases occur in women with inadequate screening
    2. Associated with Health Care Disparities (socioeconomic, ethnicity, Disability)

III. Protocol: ASCCP Calculated Risk Based Protocol

  1. Background
    1. Asymptomatic patients are stratified to testing based on risk of CIN 3 or worse (e.g. in situ, invasive Cervical Cancer)
    2. Specific risk based approach is preferred over less nuanced approach described below
  2. Risk Calculator Tools
    1. ASCCP Web Application (free with email registration)
      1. https://app.asccp.org/
    2. ASCCP Mobile Application
      1. https://www.asccp.org/mobile-app
  3. Immediate CIN 3 or greater (CIN 3+) Risk < 4%
    1. Five year CIN 3+ Risk <0.15%
      1. HPV-based testing 5 years
    2. Five year CIN 3+ Risk 0.15 to 0.54%
      1. HPV-based testing 3 years
    3. Five year CIN 3+ Risk <0.54%
      1. HPV-based testing 1 years
  4. Immediate CIN 3 or greater (CIN 3+) Risk >= 4%
    1. Immediate CIN 3+ Risk 4 to 24%
      1. Colposcopy
    2. Immediate CIN 3+ Risk 25 to 59%
      1. Expedited treatment or Colposcopy
    3. Immediate CIN 3+ Risk >60%
      1. Expedited treatment
  5. References
    1. Cheung (2020) J Low Genit Tract Dis 24(2): 90-101 [PubMed]
    2. Perkins (2020) J Low Genit Tract Dis 24(2): 102-31 [PubMed]
    3. Egeman (2020) J Low Genit Tract Dis 24(2): 132-43 [PubMed]

IV. Management: Extremely Low Risk Patients - Pap Smear not necessary

  1. Age under 21 years old
  2. Hysterectomy for benign disease (see below)
    1. Recent studies suggest no further Pap Smears needed
  3. Age >65
    1. Primary HPV Testing (or cotesting with Pap Smear) negative at age 60 and 65 years OR
    2. Three normal consecutive Pap Smears and no abnormal Pap Smears in the last 10 years (ACS)
      1. No CIN2 or greater in last 20 years

V. Management: Average Risk Patients

  1. Criteria: Average Risk
    1. Cervical Cancer Screening starts at age 21 years regardless of sexual activity
    2. Cervical Cancer Screening is not needed in very low risk patients (see above)
    3. High risk patients require more specific screening (see below)
  2. Protocol (varies by ACS, ACOG and USPHS)
    1. Initial screening age 21 to 30 years old
      1. Thin Prep Pap Smear cytology without HPV Testing
        1. Recommended every 3 years for age <30 years by USPTF
        2. No screening recommended for age <30 years by ACS
      2. Do not test HPV with Pap Smear for those under age 25 years (high transient HPV Prevalence)
        1. Those age 25-30 years may benefit from HPV Testing every 3 years
    2. Age 30 to 65 years old (with intact Uterus and Cervix)
      1. Preferred protocol (as of 2019)
        1. Primary HPV Testing without cytology OR with reflex cytology (see below)
      2. Alternative protocols
        1. Cotesting with Cytology and HPV Testing every 5 years OR
        2. Cytology alone every 3 years
    3. Age over 65 years old
      1. No screening needed if adequate negative Pap Smear history

VI. Management: Primary Cervical HPV Testing Protocol

  1. Indications
    1. Preferred for screening age 30 to 65 years at average risk of Cervical Cancer
  2. Protocol (USPTF, ACS)
    1. Recommended every 5 years if clinician collected sample
    2. Recommended every 3 years for self collected sample
  3. Self collection may be performed by patient as of 2024
    1. FDA approved self collection in health care setting in 2024
    2. Evidence for self collection in the home setting is favorable as of 2026
      1. Teal Wand home self collection was FDA approved in 2025
      2. Crane (2025) J Low Genit Tract Dis 29(1): 1-5 [PubMed]
  4. Reflex cytology (if high risk HPV detected) may be ordered on a HPV sample
    1. Higher Test Sensitivity for invasive cancer, than for Pap Smear reflex to HPV
    2. Wang (2024) Lancet Public Health 9(11): e886-95 [PubMed]
  5. Approach to HPV positive testing
    1. If HPV Genotype 16 or 18 positive
      1. Reflex to Colposcopy
    2. If HPV positive untyped or with high risk Genotype (31, 33, 35, 39, 45, 51, 52, 56, 58, 66, 68)
      1. Option 1: Reflex to cytology (ordered on HPV Test to auto-reflex)
        1. If ASCUS or greater, then reflex to Colposcopy
        2. If negative cytology, follow-up 12 months
      2. Option 2: Dual Staining for dysplasia markers (p16 and Ki-67)
        1. If positive marker stains, then reflex to Colposcopy
        2. If negative cytology, follow-up 12 months
    3. If Genotype 11 or 12 positive (or pooled, non-typed HPV positive), reflex to Cervical Cytology
      1. Obtain Colposcopy if abnormal Cervical Cytology (ASCUS or more)
  6. Efficacy
    1. Test Sensitivity 90% for cervical precancer (contrast with 50-70% for Pap Smear)
  7. References
    1. Perkins (2020) J Low Genit Tract Dis 24(2): 102-31 [PubMed]

VII. Management: High Risk Patients

  1. Protocol
    1. Start screening immunosuppressed patients within one year of onset sexual activity
    2. Specific protocols exist for history Cervical Dysplasia or cancer, high risk HPV findings
  2. High risk criteria
    1. Significant Cervical Dysplasia (CIN2, CIN3, CIS) or Cervical Cancer history
    2. In Utero Diethylstilbestrol Exposure
    3. Immunocompromised patients
    4. HIV positive
  3. Other higher risk criteria that may prompt closer monitoring
    1. Sexual activity onset before age 20 years
      1. Screen and prevent Sexually Transmitted Diseases
    2. Patients with three or more lifetime sexual partners
    3. History of HPV or other Sexually Transmitted Disease
    4. Tobacco Abuse

VIII. Management: After Hysterectomy with Cervix removed

  1. Total Hysterectomy without uterine or Cervical Cancer
    1. No further Cervical Cancer Screening
  2. Total Hysterectomy related to cancer history
    1. Continue screening for 20 years
    2. Obtain vaginal cytology every 3 years (or cotesting with HPV every 5 years)

IX. Efficacy: Pap Smear Screening for Cervical Cancer

  1. USPSTF Strength of Recommendation: A
  2. Original slide testing had issue of False NegativePap Smears
    1. Importance
      1. Accounts for 30% of U.S. Cervical Cancer cases/years
      2. Accounts for 3,700 Cervical Cancer cases/year
    2. Causes
      1. Incomplete transformation zone sampling
      2. Poorly prepared slide (e.g. drying artifact)
      3. Cytotechnologist failure to detect abnormality
        1. Now limited to 100 slides per day for review
        2. Now 10% of "normal" slides re-screened
  3. Adjunctive methods to decrease False Negative Rate
    1. General
      1. Adjuncts identify more LGSIL lesions, but may lead to over-testing
    2. Liquid-Based/Thin-Layer Preparation
      1. Improves cell sample and fixation
      2. Commercial Tests
        1. Thin Prep
        2. AutoCyte Prep (TriPath)
    3. Computer-Assisted Screening
      1. AutoPap: Scores slide on likeliood of abnormality
      2. AutoCyte: Presents cell images to cytopathologist
    4. HPV Testing
      1. See HPV Test
      2. Not recommended outside age of 25 to 65 years old, or if Immunocompromised
  4. References
    1. Nuovo (2001) Am Fam Physician 64:780-6 [PubMed]

X. Resources

  1. ASCCP Risk Tools
    1. https://www.asccp.org/mobile-app

XI. References

  1. (2002) JAMA 287:2120 [PubMed]
  2. (2002) CA Cancer J Clin 52:342-62 [PubMed]
  3. (1995) Int J Gynaecol Obstet 49:210-11 [PubMed]
  4. Burness (2020) Am Fam Physician 102(1): 39-48 [PubMed]
  5. Rerucha (2018) Am Fam Physician 97(7): 441-8 [PubMed]
  6. Sawaya (2015) Ann Intern Med 162(12):851-9 +PMID: 25928075 [PubMed]
  7. Smith (2000) CA Cancer J Clin 50:34-49 [PubMed]
  8. Wiser (2026) Am Fam Physician 113(2): 137-44 [PubMed]
  9. Zoorob (2001) Am Fam Physician 63(6):1101-12 [PubMed]
  10. Woolf (1996) USPSTF Clinical Preventive Services, p.105
  11. (1997) ACOG Opinion, no. 185

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