Should I refer a patient with a positive high‑risk HPV (genotypes 16 and 18) test to gynecology for colposcopic evaluation?

HPV 16/18 Positive: Immediate Colposcopy Referral Required

Yes, refer your patient immediately to gynecology for colposcopy, regardless of cytology results, because HPV genotypes 16 and 18 carry a 17-21% 10-year cumulative risk of CIN 3+ and are responsible for the majority of cervical cancers. 1

Why Immediate Referral is Mandatory

• The CDC explicitly recommends colposcopy in all cases of HPV 16 or 18 positive results, even if cytology is normal, due to the high association with cancer 1
• Women with HPV 16 or 18 have a 17-21% 10-year cumulative risk of CIN 3+, which far exceeds the 8-10% threshold that triggers immediate colposcopic referral 1
• This risk is dramatically higher than the 1.5-3% risk seen with other high-risk HPV types, making the conservative "wait 12 months" approach inappropriate for HPV 16/18 1

Colposcopy Protocol Specifics

• For HPV 18 specifically, endocervical sampling is strongly recommended at the time of colposcopy because HPV 18 is more strongly associated with adenocarcinoma, which can be missed without endocervical evaluation 1
• If cytology shows HSIL in addition to HPV 16 positivity, expedited treatment should be considered rather than just diagnostic colposcopy 1
• The colposcopic examination should include endocervical sampling to rule out adenocarcinoma, particularly given HPV 18's association with this difficult-to-detect cancer 1

Evidence Supporting Immediate Referral

• Recent data from 2020 showed that immediate HPV 16/18/45 genotyping with early colposcopic referral led to diagnosis of three low-stage cervical adenocarcinomas that would have been missed with delayed follow-up 2
• Among HPV 16/18/45-positive patients with negative cytology, 11.5% had CIN2+ lesions on biopsy, compared to only 3.6% in those negative for these genotypes 2
• A 2021 study found that 6.5% of women with non-16/18 high-risk HPV and negative cytology had CIN 2+ lesions, and one patient with HPV 39 had invasive cervical cancer, supporting the even higher risk with HPV 16/18 3

Critical Distinction from Other HPV Types

• Do not confuse management of HPV 16/18 with other high-risk HPV types - the latter can be managed with repeat co-testing at 12 months, but HPV 16/18 requires immediate action 1
• Approximately 60% of non-16/18 high-risk HPV infections clear spontaneously within 12 months, but HPV 16/18 infections are more persistent and carry substantially higher cancer risk 1
• The 2012 ACS/ASCCP guidelines explicitly endorse immediate colposcopy for HPV 16/18 positive results as the standard of care 1

Post-Colposcopy Management

• If CIN 2+ is detected, treatment options include ablative or excisional procedures 1
• After treatment for high-grade precancer, surveillance must continue for at least 25 years with HPV testing or co-testing at 6,18, and 30 months initially, then at 3-year intervals 1
• If colposcopy is negative but HPV 16/18 remains positive, closer follow-up is warranted compared to other HPV types 1

Common Pitfall to Avoid

• Never delay colposcopy to "repeat testing in 12 months" for HPV 16/18 positive patients - this is the management for other high-risk HPV types only, and applying it to HPV 16/18 can result in missed cancers and progression of high-grade lesions 1, 2