What are the next steps after an abnormal Pap (Papanicolaou) smear?

Management of Abnormal Pap Smear

The next steps after an abnormal Pap smear depend critically on the specific cytology result and patient age, with high-grade lesions (HSIL, ASC-H, AGC, AIS) requiring immediate colposcopy, while ASC-US and LSIL offer multiple management pathways including HPV testing, repeat cytology, or colposcopy based on clinical context. 1

Immediate Colposcopy Required

The following results mandate immediate referral to colposcopy with directed biopsy: 1

• High-grade squamous intraepithelial lesion (HSIL)
• Atypical squamous cells, cannot exclude HSIL (ASC-H)
• Atypical glandular cells (AGC)
• Adenocarcinoma in situ (AIS)
• Any history of previous high-grade lesions (CIN 2/3) 1

For HPV 16 or 18 positive results on primary HPV screening, colposcopy is recommended even with normal cytology, as HPV 16 carries the highest cancer risk. 1 For HPV 18 specifically, endocervical sampling should be performed at colposcopy due to its association with adenocarcinoma. 1

ASC-US Management (Age ≥21 Years)

For atypical squamous cells of undetermined significance, three evidence-based options exist: 1

1. High-risk HPV DNA testing (preferred when available)

   • If HPV positive: immediate colposcopy 1
   • If HPV negative: repeat Pap at 12 months 1

2. Repeat cytology at 6 and 12 months

   • Continue until two consecutive negative results 1
   • If any repeat shows ASC-US or worse: proceed to colposcopy 1

3. Immediate colposcopy

   • Appropriate when adherence concerns exist or patient preference after shared decision-making 1
   • High-grade histology detected in <12% of ASC-US cases 1

Important caveat: ASC-US with severe inflammation should be re-evaluated after 2-3 months, with treatment of identified infections before repeat testing. 1

LSIL Management (Age ≥21 Years)

For low-grade squamous intraepithelial lesion: 1

• Colposcopy with directed biopsy is the standard approach 1
• Alternative: Repeat cytology every 4-6 months for 2 years until three consecutive negatives, but only for carefully selected patients with reliable follow-up 1
• Research shows 13-22% of LSIL cases progress to CIN2/3 on colposcopy 2

Critical exception: Women under age 21 with ASC-US or LSIL should NOT undergo colposcopy due to high spontaneous clearance rates; repeat Pap testing at 12 and 24 months is recommended instead. 1

Primary HPV Screening Results

When HPV testing is used as primary screening: 1

• HPV 16 positive: Colposcopy regardless of cytology; consider expedited treatment for HSIL cytology 1
• HPV 18 positive: Colposcopy regardless of cytology with endocervical sampling 1
• Other high-risk HPV positive with normal cytology: Return in 1 year for repeat testing 1
• Two consecutive HPV-positive tests: Colposcopy always recommended, regardless of previous Pap results 1

Post-Treatment Surveillance

After treatment for high-grade precancer (CIN 2/3): 1

• Initial surveillance: HPV test or cotest at 6,18, and 30 months (or cytology alone at 6,12,18,24, and 30 months) 1
• Long-term surveillance: Continue for at least 25 years, even beyond age 65 1
• Testing intervals: Every 3 years with HPV/cotest, or annually with cytology alone 1
• If hysterectomy occurs during surveillance, continue vaginal screening 1

Referral and Follow-Up Systems

Critical implementation points: 1

• Clinics unable to provide colposcopy must establish referral protocols with prompt evaluation and results reporting back to referring provider 1
• Develop tracking systems to identify patients who miss appointments 1
• Document all results, referrals, and follow-up outcomes clearly in medical records 1
• Consider establishing colposcopy services in health departments where referrals are difficult 1

Common Pitfalls to Avoid

• Never use low-risk HPV testing for clinical management—it provides no benefit 1
• Negative HPV or cotest results only defer colposcopy if performed for screening purposes within 5 years, not if done for surveillance of previous abnormalities 1
• Do not discontinue screening in women with history of abnormal results, even after age 65, if 25-year surveillance period incomplete 1, 3
• Menstruation does not preclude liquid-based cytology, though conventional cytology should be postponed 1
• Research demonstrates that AGUS (atypical glandular cells) carries 25% risk of clinically significant cervical or uterine lesions and requires intensive evaluation including colposcopy with endocervical curettage and endometrial sampling 4