Human papillomavirus (HPV) DNA testing is globally recommended in primary cervical cancer screening. Effective triaging of HPV-positive women plays a crucial role for detection cancer precursors. p16/Ki67 has been studied for distinguishing of high-grade cervical intraepithelial lesion (HSIL) risk by co-expression of anti-proliferative/proliferative markers. We investigated a diagnostic value of p16/Ki67 as the second-step in HPV-based screening.
From 8824 cervical cancer screening tests (including 1718 cotesting, 345 LBC with reflex HPV and 372 p16/Ki67 tests), a group of 189 cases was selected based on 4 end-points: positive high-risk HPV status, LBC and double immunocytochemical p16/Ki67 test (DS) in automated preparation systems and performed colposcopy with biopsy as follow-up.
Total number of histologic HSIL/DS positivity was 33/30 - for positive 16 or 18 types HPV (16/18HPV+) 21/20 and for positive non-16 or non-18 types (n16/n18HPV+) 12/10, for histologic LSIL was 70/23 - for 16/18HPV+ 28/12 and for n16/n18HPV+ 42/11, and for negative was 84/16 – for 16/18HPV+ 37/10 and for n16/n18HPV+ 47/6. Sensitivity/specificity/PPV/NPV of DS for hHSIL were 91/74/42/97 respectively. In retrospective analysis, total number of biopsies needed in p16/Ki67-based triage was 71 comparing to 180 in LBC-based triage.
p16/Ki67 can be a clinically important diagnostic test for detecting hHSIL in HPV-positive women that may reduce number of performed invasive procedures and increase patients comfort. In consequence, incorporating of p16/Ki67 test clinical algorithms could reduce total costs of secondary cervical cancer prevention.