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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, 6–12 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

  1. 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.
  2. Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: USPSTF recommendation statement. JAMA. 2018;320(7):674-686.
  3. 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.
  4. 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. ```