High-risk human papillomavirus DNA test and p16INK4a in the triage of LSIL: A prospective diagnostic study

Abstract Objective. The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16 INK4a immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16 INK4a in the triage of a population of HR-HPV positive LSIL. Methods. We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16 INK4a immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+. Results. A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16 INK4a had significantly higher specificity of 89% ( p =0.0000) but low sensitivity of 42%. The role of p16 INK4a immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16 INK4a triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone ( p =0.4). Conclusions. The results indicate that HR-HPV or p16 INK4a cannot be used as solitary markers for the assessment of LSIL. The addition of p16 INK4a immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL.