USPSTF updated guidance on cervical cancer screening
Melnikow J, Henderson JT, Burda BU, et al. Screening for cervical cancer with high-risk human papillomavirus testing: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;320:687-705.
US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:674-686.
Past guidelines for cervical cancer screening have included testing for high-risk HPV (hrHPV) as a cotest with cytology or for triage of atypical squamous cells of undetermined significance (ASCUS) in women aged 30 to 65 years.8 The American Society for Colposcopy and Cervical Pathology and the Society of Gynecologic Oncology, with other stakeholder organizations, issued interim guidance for primary HPV testing--that is, HPV test first and, in the case of non-16/18 hrHPV types, cytology as a triage. The most recent evidence report and systematic review by Melnikow and colleagues for the USPSTF offers an in-depth analysis of risks, benefits, harms, and value of cotesting and other management strategies.9
Focus on screening effectiveness
Large trials of cotesting were conducted in women aged 25 to 65.10-13 These studies all consistently showed that primary hrHPV screening led to a statistically significant increased detection of cervical intraepithelial neoplasia (CIN) 3+ in the initial round of screening, with a relative risk of detecting CIN 3+ ranging from 1.61 to 7.46 compared with cytology alone.
Four additional studies compared cotesting with conventional cytology for the detection of CIN 3+. None of these trials demonstrated a significantly higher detection rate of CIN 3+ with cotesting compared with conventional cytology testing alone. Notably, the studies reviewed were performed in European countries that had organized screening programs in place and a nationalized health care system. Thus, these data may not be as applicable to women in the United States, particularly to women who have limited health care access.
Risks of screening
In the same studies reviewed for screening effectiveness, the investigators found that overall, screening with hrHPV primary or cotesting was associated with more false-positive results and higher colposcopy rates. Women screened with hrHPV alone had a 7.9% referral rate to colposcopy, while those screened with cytology had a 2.8% referral rate to colposcopy. Similarly, the rate of biopsy was higher in the hrHPV-only group (3.2% vs 1.3%).
Overall, while cotesting might have some improvement in performance compared with hrHPV as a single modality, there might be risks of overreferral to colposcopy and overtreatment with additional cytology over hrHPV testing alone.
This evidence review also included an analysis of more potential harms. Very limited evidence suggests that positive hrHPV test results may be associated with greater psychological harm, including decreased sexual satisfaction, increased anxiety and distress, and worse feelings about sexual partners, than abnormal cytology results. These were assessed, however, 1 to 2 weeks after the test results were provided to the patients, and long-term assessment was not done.
New recommendations from the USPSTF
Based on these data, the USPSTF issued new recommendations regarding screening (TABLE).14 For women aged 21 to 29, cytology alone should be used for screening every 3 years. Women aged 30 to 65 can be screened with cytology alone every 3 years, with hrHPV testing alone every 5 years, or with cotesting every 5 years.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Primary screening with hrHPV is more effective in diagnosing a CIN 3+ than cytology alone. Cotesting with cytology and hrHPV testing appears to have limited performance improvement, with potential harm, compared with hrHPV testing alone in diagnosing CIN 3+. The Task Force recommendation is hrHPV testing alone or cotesting every 5 years.
Primary screening with hrHPV is more effective in diagnosing a CIN 3+ than cytology alone. Cotesting with cytology and hrHPV testing appears to have limited performance improvement, with potential harm, compared with hrHPV testing alone in diagnosing CIN 3+. The Task Force recommendation is hrHPV testing alone or cotesting every 5 years.