Cotesting vs Cytology Alone
Four RCTs (N > 130,000 women) compared screening with cytology alone vs cotesting (cytology in combination with hrHPV testing): the NTCC Phase I trial in Italy, 28,32,34 Swedescreen in Sweden, 36,37 A Randomized Trial in Screening to Improve Cytology (ARTISTIC) in the United Kingdom, 38-40 and the Population-Based Screening Study Amsterdam (POBASCAM) in the Netherlands. 41 In all 4 trials, the cumulative relative ratio of CIN 3+ detection between the 2 strategies (cotesting vs cytology alone) were not statistically significant after 2 rounds of screening. The NTCC Phase I, ARTISTIC, and POBASCAM trials reported 2 rounds of screening at 3- to 5-year intervals, whereas Swedescreen reported 1 round of screening with registry follow-up at 3 years. Two trials (Swedescreen and POBASCAM) reported no difference between screening strategies at 13 to 14 years of follow-up.
These 4 trials reported hrHPV positive rates of 7% to 22% for screening with cotesting; again, rates were highest among women younger than 30 or 35 years. Colposcopy rates were higher for screening with cotesting than for cytology alone in 2 trials (ARTISTIC and NTCC Phase I) and not reported in the other 2 trials (Swedescreen and POBASCAM). False-positive rates were higher for screening with cotesting in 3 of 4 trials (Swedescreen did not report the false-positive rate for the intervention group).
The ARTISTIC trial also surveyed a subsample of patients (N = 2508) about the psychological effects of screening. 42 It found no difference in distress or anxiety between women screened with cotesting and women screened with cytology alone. Women in the cotesting group who were notified of positive HPV results reported lower sexual satisfaction regardless of their cytology results, but there were no statistically significant differences in psychological distress or anxiety between study groups. 38 A separate cross-sectional study used a survey to evaluate the psychological effects of screening with hrHPV cotesting in women aged 20 to 64 years (N = 428) and found that women who received a positive HPV result were more distressed and had more negative feelings about their sexual partners than women who received a negative HPV result. 43
Additional Evidence From Observational Studies
In addition to RCTs, the USPSTF also reviewed evidence from an individual participant data meta-analysis that pooled patients from 4 trials (NTCC Phase I, Swedescreen, ARTISTIC, and POBASCAM), as well as a single trial of primary hrHPV testing (NTCC Phase II). The meta-analysis found a 40% lower incidence of invasive cervical cancer among patients screened with some form of hrHPV testing compared with cytology alone. 44 Biopsy rates from the individual participant data meta-analysis suggest that these higher colposcopy rates led to higher rates of biopsy with cotesting than with cytology alone. However, since the meta-analysis pooled data from trials with distinctly different screening strategies and hrHPV test types, these findings cannot be interpreted with certainty.
The trial evidence was also supplemented with results from 4 cohort studies. One study considered primary hrHPV screening, 45 2 studies considered cotesting, 46-51 and 1 reported on cotesting among underscreened women. 52 These outcomes were not notably different from the trial outcomes. A recently published report on women (N = 1,262,713) screened 1 or more times in Kaiser Permanente Northern California between 2003 and 2015, which included women aged 25 to 29 years screened with cytology and triage with hrHPV testing for atypical squamous cells of undetermined significance and women aged 30 to 77 years screened with cotesting, also suggests that women who test negative for hrHPV have very low rates of subsequent CIN 3+, regardless of cytology results. 53 It is important to note that women younger than 30 or 35 years had higher hrHPV-positive and CIN 3+ rates, facts about Bordeaux women accompanied by higher colposcopy rates.
