What are the management and follow-up recommendations for a patient with negative cytology (cell study), no visible transformation zone, and a negative Human Papillomavirus (HPV) test?

From the Guidelines

For a patient with negative cytology, no visible transformation zone, and a negative HPV test, routine screening can be resumed with follow-up in 3-5 years depending on age. This recommendation is based on the latest guidelines, including those from the 2021 sexually transmitted infections treatment guidelines 1, which emphasize risk-based management for abnormal cervical cancer screening tests. The key factors guiding this decision are the negative cytology and negative HPV test results, which together indicate a very low risk for cervical cancer or precancerous lesions.

The absence of a visible transformation zone, while it may complicate colposcopic evaluation, does not change the management approach when both cytology and HPV testing are negative. According to the guidelines, the focus is on the risk level for CIN 3, rather than the specific test results, allowing for personalized management recommendations 1.

For patients under 30, follow-up in 3 years with cytology alone is typically recommended, while for those 30 and older, co-testing or primary HPV testing in 5 years is appropriate, as outlined in the risk-based management consensus guidelines 1. This approach strikes a balance between the need for ongoing surveillance and the avoidance of unnecessary procedures in a patient with a very low risk of developing cervical cancer in the near term.

Key points to consider in management include:

• Negative cytology and HPV test results indicate low risk.
• The absence of a visible transformation zone does not alter management in this context.
• Follow-up intervals are based on age and prior test results.
• The risk-based management approach allows for personalized recommendations.
• Guidelines recommend against immediate interventions or additional testing for patients with negative cytology and HPV test results 1.

From the Research

Management and Follow-up Recommendations

• For a patient with negative cytology, no visible transformation zone, and a negative Human Papillomavirus (HPV) test, the management and follow-up recommendations can be based on existing guidelines and studies 2, 3, 4, 5, 6.
• A study published in 2002 found that the absence of a transformation zone component in a screening ThinPrep Papanicolaou test was not associated with missed high-grade lesions, and therefore, repeat screening of reproductive-aged women with negative liquid-based tests and no cytologic evidence of a transformation zone component is not recommended 4.
• Another study published in 2020 estimated the 5-year risks of cervical precancer after one, two, and three negative cotests among women aged 55-64 years undergoing routine cotesting, and found that these risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s) 2.
• A 2019 study compared HPV testing with routine cytology in cervical screening and found that a longer screening interval after a negative HPV test than after a negative cytology test is justified, and that about three-quarters of women with HPV infection and normal cytology clear their infections within about 3 years 3.

Screening Intervals and Triage Policy

• The choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening 2.
• A study published in 2019 suggested that a more sensitive HPV test is needed to detect occult CIN3 at high risk of progression to cancer, but this would substantially increase the overall HPV detection rate 3.
• HPV assays that identify HPV types 31,33,45,52, and 58 in addition to 16 and 18 could be useful in triage as well as in primary HPV testing 3.
• Post-colposcopy HPV mRNA testing was found to be as sensitive but more specific than post-colposcopy cytology, and could justify treatment in women above 40 years 6.

Patient Management

• Patients and providers may be reassured with negative HPV testing, but long-term management of positive HPV testing (especially in conjunction with negative cytology) is unclear 5.
• Women with negative cervical biopsy require follow-up before resumption of routine screening, and post-colposcopy HPV mRNA testing could be used in this setting 6.