What are the next steps for a patient with a positive HPV (Human Papillomavirus) Aptima test result, indicating the presence of high-risk HPV types?

Management of Positive HPV Aptima Test with Negative Genotyping

For a patient with positive HPV Aptima (detecting high-risk HPV mRNA) but negative for HPV 16,18, and 45 genotyping, the next step depends critically on the cytology result and patient age.

When Cytology is Normal (Negative Pap)

For Women Age 30 and Older

Repeat co-testing (HPV and cytology) in 12 months is the recommended approach 1, 2. This allows time for potential spontaneous clearance of the HPV infection while maintaining appropriate surveillance 2.

• At 12-month follow-up:

  • If both HPV and cytology are negative: return to routine screening intervals 1
  • If HPV remains positive but cytology is negative: repeat co-testing in another 12 months or proceed to colposcopy if persistence is concerning 1
  • If cytology shows ASC-US or worse: proceed directly to colposcopy 1, 2

• Do NOT extend the screening interval beyond 12 months for this initial follow-up, as appropriate surveillance is critical 1

• Immediate colposcopy is NOT indicated when cytology is normal and only non-16/18/45 high-risk types are present 1, 2

For Women Under Age 30

• Annual Pap testing is recommended, as HPV infections are highly prevalent and typically transient in this age group 2
• HPV testing is not typically used for primary screening in women under 30 2

When Cytology is Abnormal

Any abnormal cytology result (ASC-US or worse) requires immediate colposcopy 3, 2, regardless of which specific high-risk HPV types are present.

• For ASC-US with positive high-risk HPV: colposcopy is indicated 3
• For LSIL, ASC-H, or HSIL: immediate colposcopy 3
• For AGC (atypical glandular cells): follow specific AGC management protocols 3

Clinical Context and Rationale

Why This Approach Matters for Outcomes

• The Aptima HPV mRNA test detects E6/E7 oncogene expression, which indicates active viral transcription and higher specificity for clinically significant disease compared to DNA testing 4, 5
• Women with positive HPV mRNA have a 29.7% cumulative incidence of HSIL or worse, while mRNA-negative women have 0% risk 5
• Early detection through appropriate surveillance prevents progression to invasive cancer while avoiding overtreatment of transient infections 2

Important Caveats

• HPV positivity does not mean cervical cancer is present—it indicates increased surveillance is needed to prevent progression 2
• Most HPV infections clear spontaneously, which is why repeat testing rather than immediate intervention is appropriate when cytology is normal 2
• Never recommend hysterectomy or excisional procedures based solely on a positive HPV test without histologic confirmation of high-grade disease 1

Special Circumstances Requiring Modified Management

Annual screening is required regardless of HPV status for women with: 2

• History of cervical disease (CIN 2/3)
• HIV infection
• Immunosuppression
• DES exposure

If Reactive Changes or Candida Present

• Treat symptomatic infections, but this does not eliminate the need for follow-up testing 1, 6
• Reactive changes can potentially mask underlying abnormalities 6
• Repeat testing at 6-12 months after treatment allows inflammatory changes to resolve for more accurate evaluation 6

Key Pitfall to Avoid

Do not assume that negative genotyping for HPV 16/18/45 means the patient is low-risk. The Aptima test detects 14 high-risk HPV types (16,18,31,33,35,39,45,51,52,56,58,59,66,68), and other high-risk types besides 16/18/45 can cause high-grade lesions and cancer 4, 7. The positive mRNA result indicates active oncogenic viral activity requiring surveillance 4, 5.