Abnormal Pap Smear Results: Significance and Management
ASC-US (Atypical Squamous Cells of Undetermined Significance)
Reflex HPV DNA testing is the preferred management strategy for ASC-US, with immediate colposcopy for HPV-positive patients and repeat co-testing in 1 year for HPV-negative patients. 1, 2
Clinical Significance
- ASC-US represents approximately 4% of all cervical cytology smears and carries a 9.7% risk of underlying high-grade cervical disease (CIN 2 or worse) 1, 2
- Despite the benign-sounding name, more than 40% of high-grade lesions (CIN II/III or cancer) can be discovered within atypical cytology categories 3
Management Algorithm
- HPV-positive ASC-US: Proceed directly to colposcopy, as this carries an 18% 5-year risk of histologic HSIL and cancer 1, 2
- HPV-negative ASC-US: Repeat co-testing (Pap plus HPV) in 1 year; if both remain negative, return to routine age-appropriate screening 1, 2
- Reflex HPV testing identifies 92.4% of women with CIN III while reducing unnecessary colposcopy referrals to 55.6% compared to 67.1% with repeat cytology alone 2
Critical Pitfalls
- Never delay follow-up beyond 180 days, as delays are associated with increased risk of progression and delayed cancer diagnosis 2
- Do not exit screening at age 65 with a recent ASC-US result, even if HPV-negative, as this is insufficient for safe screening cessation 4
LSIL (Low-Grade Squamous Intraepithelial Lesion)
All women with LSIL should be referred for colposcopy, as 80-85% are high-risk HPV positive. 3
Clinical Significance
- LSIL is almost synonymous with HPV infection, with the vast majority testing positive for high-risk HPV types 3
- LSIL represents a lower cancer risk than higher-grade lesions but still requires evaluation to exclude concurrent high-grade disease 3
Management Algorithm
- Immediate colposcopy with directed biopsy is recommended for all women with LSIL 3
- If colposcopy shows only CIN 1 and original cytology was LSIL (not HSIL), follow-up with cytology at 6 and 12 months or HPV DNA testing at 12 months is acceptable 3
- If CIN 1 persists for at least 2 years, continued observation or treatment are both options 3
ASC-H (Atypical Squamous Cells – Cannot Exclude HSIL)
Women with ASC-H require immediate colposcopy regardless of HPV status, as 40-48% have high-grade squamous intraepithelial lesions on biopsy. 2, 5
Clinical Significance
- ASC-H is an uncommon interpretation (less common than ASC-US) but carries significantly higher risk 5
- The positive predictive value for CIN 2 or worse ranges from 27.2% to 40.5%, with most lesions being CIN 3 5
- Oncogenic HPV DNA is detected in 69.8-85.6% of ASC-H cases 5
Management Algorithm
- Never use HPV testing to triage ASC-H – these patients require immediate colposcopy with directed biopsy 2
- The high positive predictive value for high-grade lesions justifies immediate colposcopic evaluation without preliminary HPV testing 5
HSIL (High-Grade Squamous Intraepithelial Lesion)
HSIL management is the least controversial: immediate referral for colposcopy with directed biopsy and generally treatment. 3
Clinical Significance
- CIN 3 (the histologic correlate of HSIL) is considered a true cancer precursor, with approximately 12% progressing to invasive cancer if untreated 3
- About 33% of CIN 3 lesions regress spontaneously, while the remainder persist as CIN 3 3
Management Algorithm
- For women with CIN 2,3 and satisfactory colposcopy, ablation or diagnostic excision is acceptable 3
- Observation is unacceptable for non-pregnant, non-adolescent women with CIN 2,3 3
- If colposcopy is unsatisfactory or if CIN 2,3 recurs, diagnostic excision is mandatory 3
Post-Treatment Surveillance
- HPV testing has the highest negative predictive value (98%) for detecting residual or recurrent disease after treatment, superior to negative resection margins (91%) or cervical cytology alone (93%) 3
- Women who remain HPV-positive after treatment for CIN 2,3 are at significantly increased risk of recurrent or residual CIN 3
AGC (Atypical Glandular Cells)
All women with AGC require immediate colposcopy with endocervical sampling and HPV DNA testing, as up to 38% have significant squamous or glandular lesions. 3
Clinical Significance
- AGC represents only 0.2% of cytologic smears but carries disproportionately high risk 3
- Although benign lesions are most common, CIN is the most frequent pathology, especially in women younger than 35 years 3
- HPV positivity in AGC has a high positive predictive value, with 20% of women having CIN 3 or cancer on biopsy 3
Management Algorithm
- Initial evaluation includes: colposcopy with endocervical sampling AND HPV DNA testing for all AGC subcategories 3
- Endometrial sampling is also required for women 35 years and older, or younger women with risk factors for endometrial cancer 3
- Reflex HPV testing or repeat cytology alone is unacceptable as initial triage for AGC-NOS, AGC-favor neoplasia, or AIS 3
Follow-Up After Initial Negative Evaluation
- If HPV-positive: repeat cytology and HPV testing at 6 months 3
- If HPV-negative: repeat cytology and HPV testing at 12 months 3
- If both HPV and cytology are negative on re-evaluation, annual cytologic testing may resume 3
- If AGC-favor neoplasia or AIS: excisional procedure may be required despite initial negative testing 3
Carcinoma
Any cytology showing invasive carcinoma requires immediate referral to gynecologic oncology for comprehensive evaluation and staging. 3
Clinical Significance
- Invasive carcinoma on cytology represents the highest-risk category and requires urgent subspecialty management 3
- Mean age of patients with invasive carcinoma is approximately 57 years 6
Special Population Considerations
HIV-Infected Women
- All HIV-infected women with ASC-US or ASC-H should undergo immediate colposcopy, regardless of HPV status 2
- HIV-infected women have 10-11 times higher rates of abnormal cervical cytology and 60% progression to SIL compared to 25% in HIV-negative women 4, 2
- More frequent screening is required: twice during the first year after HIV diagnosis, then annually if normal 2
Women Aged 21-24 Years
- Conservative management is recommended due to high rates of HPV infection and spontaneous regression in this age group 3, 2
- Co-testing is not recommended for screening in women aged 21-29 years 3
Pregnant Women
- Colposcopic biopsy should be performed only for lesions suspicious for cancer or CIN 2/3 3, 2
- Avoid unnecessary biopsies of low-grade appearing lesions during pregnancy 2