For a sexually active adult (any gender) with a positive high‑risk HPV DNA test for types 18 and 45, what are the recommended next steps in evaluation and management?

Management of HPV 18/45 Infection

For any sexually active adult testing positive for HPV types 18 or 45, immediate colposcopy with endocervical sampling is mandatory regardless of cytology results, due to the exceptionally high risk of adenocarcinoma associated with these specific genotypes. 1, 2

Immediate Management Algorithm

Step 1: Colposcopy with Endocervical Sampling

• Proceed directly to colposcopy for HPV 18 or 45 positivity, even when cytology is completely normal, because these types carry a 14% risk of CIN 3+ lesions and are strongly associated with cervical adenocarcinoma 2, 3
• Perform endocervical curettage at the time of colposcopy specifically because HPV 18 and 45 have a predilection for glandular cells in the endocervical canal, where adenocarcinoma develops 1, 2
• During colposcopy, examine the entire cervix with acetic acid and Lugol's iodine, obtaining biopsies of any suspicious areas 2
• HPV types 16,18, and 45 together account for 94% of all cervical carcinomas, with HPV 18 and 45 particularly linked to adenocarcinoma 4, 3

Step 2: Risk Stratification Based on Findings

If colposcopy and biopsy are negative (no CIN detected):

• Repeat HPV testing or co-testing (HPV plus cytology) at 12 months 1, 2
• HPV testing or co-testing is strongly preferred over cytology alone for follow-up because negative HPV testing is less likely to miss disease 1, 2
• If HPV remains positive at 12 months, repeat colposcopy 1
• If both HPV and cytology are negative at 12 months, return to routine screening 1

If CIN 2 or higher is detected:

• Proceed with ablative or excisional treatment procedures 1, 2
• After treatment for high-grade precancer, surveillance must continue for at least 25 years 1, 2
• Initial post-treatment testing includes HPV test or co-test at 6,18, and 30 months 1, 2
• Long-term surveillance includes testing at 3-year intervals if using HPV testing or co-testing, or annual testing if using cytology alone 1

Special Considerations for HPV 18/45

Why These Types Require Aggressive Management

• Women with HPV 18 have approximately 14% risk of CIN 3+ lesions, compared to only 3% for other non-16/18 high-risk HPV types 2
• HPV 16 carries a 17-21% 10-year cumulative risk of CIN 3+, while non-16/18 types carry only 1.5-3% risk 1
• Among HPV-positive individuals, 99% of prevalent adenocarcinoma and 96% of adenocarcinoma in situ are linked to HPV types 16,18, or 45 3
• The concurrent detection of HPV 16/18/45 with atypical glandular cells (AGC) cytology predicts a 12% absolute risk of adenocarcinoma/AIS with an odds ratio of 1341 compared to other high-risk HPV types 3

Gender-Specific Considerations

• For individuals with a cervix (cisgender women, transgender men, non-binary individuals), follow the colposcopy pathway outlined above 1, 2
• For individuals without a cervix but with potential HPV exposure sites (anal canal, oropharynx), HPV 18/45 positivity warrants evaluation by appropriate specialists, though specific screening protocols for these sites are less well-established 5

Critical Pitfalls to Avoid

• Do not delay colposcopy for HPV 18 or 45 positive results by scheduling repeat testing at 12 months; this conservative approach is only appropriate for non-16/18/45 high-risk HPV types 1, 2
• Do not omit endocervical sampling during colposcopy, as HPV 18 and 45 have specific tropism for glandular cells that may be missed by ectocervical biopsy alone 1, 2
• Do not rely on cytology alone for follow-up after negative colposcopy; HPV testing or co-testing is mandatory because negative HPV testing provides superior reassurance 1, 2
• Do not perform treatment based on HPV result alone without histologic confirmation of disease through biopsy 1

Vaccination Considerations

• HPV vaccination is recommended for catch-up through age 26 years for all persons 6
• For adults aged 27-45 years, shared clinical decision-making is recommended regarding potential HPV vaccination, recognizing that some persons not adequately vaccinated might be at risk for new HPV infection 6
• Current 9-valent HPV vaccine (Gardasil 9) protects against HPV types 16,18,31,33,45,52, and 58, as well as types 6 and 11 that cause genital warts 6
• Vaccination does not modify screening intervals or methods for those already infected 7
• HPV testing should not be used to determine vaccination eligibility 7