Cervical cancer screening trials and observational studies have demonstrated that HPV testing provides high negative predictive value, which allows safely extending screening intervals for HPV-negative women. The challenge lies in discriminating between transient HPV infections and prevalent precancers in HPV-positive women. An implementation study was conducted at Kaiser Permanente Northern California (KPNC) to evaluate two candidate triage strategies, p16/Ki-67 dual stain and HPV16/18 genotyping.
Over 13,000 HPV-positive women who participated in cervical cancer screening at KPNC were enrolled from 2015 to 2016. All women were tested for HPV using the hybrid capture 2 assay and had Pap results based on Surepath liquid based cytology. p16/Ki-67 dual stain was performed on residual Surepath specimens using the CINtec PLUS assay. HPV16/18 genotyping was based on the cobas assay. All testing was implemented and conducted at KPNC. Baseline results for 7,124 women are reported. Since HPV-positive, cytology-negative women have a repeat co-test after 12 months before referral to colposcopy, detection of CIN3 is currently only evaluated for dual stain and HPV16/18 as repeat cotest results are not yet available.
Among all 7,124 HPV-positive women, 4,107 (57.7%) were cytology-positive (ASC-US or higher), 3056 (42.9%) were dual stain positive, and 1406 (19.7%) were positive for HPV16 or HPV18. Among all 3,017 HPV-positive, cytology-negative women, 911 (30.2%) were dual stain positive, and 508 (16.8%) were positive for HPV16 or HPV18. Of 315 CIN3 detected so far, 280 (88.9%) were dual stain positive and 176 (55.9%) were positive for HPV16 or HPV18. Additional disease ascertainment, especially among HPV-positive, cytology-negative women, is still ongoing.
At KPNC, primary HPV screening and dual stain triage of HPV-positives would reduce colposcopy referral compared to HPV-cytology co-testing while achieving high sensitivity. While HPV16/18 testing would reduce colposcopy referral in comparison to dual stain testing, almost half of the prevalent CIN3s would be missed. Additional follow-up is required to evaluate the programmatic performance of both approaches, assessing disease detection and number of colposcopies combining baseline and 1-year repeat co-tests.