Management of Normal Cervical Cytology with Negative HPV mRNA E6/E7 and Negative STI Testing

Return to routine age-appropriate cervical cancer screening based on the patient's age and screening history. 1

Immediate Management

No further testing or intervention is required at this time. 1 The combination of negative cytology and negative HPV testing provides the highest level of reassurance against current or near-term cervical disease.
Negative Chlamydia trachomatis and Neisseria gonorrhoeae results require no treatment. 2 While co-infections with these organisms can increase risk of cervical abnormalities when HR-HPV is present, their absence alongside negative HPV testing eliminates this concern.

Resume routine screening in 5 years with co-testing (cytology plus HPV testing). 1 This is the preferred screening interval when both cytology and HPV testing are negative, as endorsed by ACS, ASCCP, and ASCP guidelines.
Alternatively, screening with cytology alone every 3 years is acceptable if co-testing is not available or preferred. 1 However, co-testing every 5 years remains the preferred strategy for this age group.

Resume routine screening in 3 years with cytology alone. 1 Co-testing is not recommended for women in this age group, even if HPV testing was performed.
HPV testing should not have been performed as part of routine screening in this age group. 1 If it was done and is negative, simply follow cytology-based screening recommendations.

Screening may be discontinued if the patient has had adequate prior screening with normal results. 1 Adequate prior screening typically means three consecutive negative cytology results or two consecutive negative co-test results within the past 10 years, with the most recent test within 5 years.

The negative predictive value of combined negative cytology and negative HPV testing approaches 99-100% for ruling out CIN 2+. 3 This provides exceptional reassurance that no clinically significant cervical disease is present.
Women with both negative cytology and negative HPV testing have substantially decreased risk of high-grade lesions compared to those with negative cytology alone. 1 The dual negative result is more reassuring than either test alone.

Women who have been vaccinated against HPV must follow the same screening recommendations as unvaccinated women. 1 Vaccination does not alter screening intervals or methods.
HPV testing should not be used to determine vaccination eligibility or effectiveness. 1

These standard screening intervals do NOT apply to immunocompromised women (including HIV-positive patients), women with history of cervical cancer, or those exposed to diethylstilbestrol in utero. 1 These populations require more frequent screening with individualized protocols.

Do not perform annual screening. 1 Annual screening is not recommended for any age group and leads to unnecessary procedures without improving outcomes.
Do not use HPV testing as a stand-alone screening test. 1 When HPV testing is performed, it should be combined with cytology (co-testing) in women aged 30-65 years.
Do not screen women younger than 21 years. 1 Cervical cancer is extremely rare in this age group, and screening causes more harm than benefit due to overtreatment of transient HPV infections.
Do not assume that negative results eliminate the need for future screening. 1 Even with negative results, women must continue age-appropriate screening at recommended intervals, as new HPV infections can occur.

Document the screening results and the recommended return interval clearly in the medical record. 1 This ensures continuity of care and appropriate recall.
Counsel patients that negative results are reassuring but do not eliminate the need for future screening. 1 Emphasize the importance of adhering to recommended screening intervals.
Inform patients that new HPV infections can occur at any time through sexual activity. 1 This reinforces the need for continued screening despite current negative results.