Dual staining for p16/Ki67 is a more specific test than cytology for triage of HPV-positive women
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Globally, cervical cancer (CC) screening is moving from cytology-based to HPV screening or a combination of both (co-testing). Most HPV-positive women clear the virus and do not develop relevant disease. Additional triage approaches are needed to reduce unnecessary colposcopy referrals. The p16/Ki67 dual stain cytology test (DSCT) is one of the most promising, but it has not (yet) been included as a recommendation in European guidelines. Previous studies in Spain on this issue are lacking. We studied the performance of p16/Ki67 DSCT for the triage of HPV-positive women in Navarra to detect precursor lesions (PLs) and CC compared to cytology only. We selected 1865 HPV-positive women with p16/Ki67 DSCT results and 304 women with an available biopsy result. Sensitivity, specificity and predictive values of the p16/Ki67 DSCT to detect underlying PLs and CC compared to cytology were calculated, using the biopsy as the gold standard. Cytology and p16/Ki67 DSCT showed similar sensitivity (99.0% vs. 98.0%), but cytology had significantly lower specificity (6.9 vs. 39.1%). Of the CIN2+/HPV+ women, triage using cytology only would have resulted in 40.2% true PLs and CC, while using p16/Ki67 DSCT this was 98.0% qualifying the women for colposcopy referral. Our results show that p16/Ki67 DSCT detects more than twice as many true PLs and CC than cytology only in this population. Thus, this test can be considered as an important additional tool in HPV testing-based screening strategies, to avoid unnecessary colposcopy referrals and to reduce health care costs.
KeywordsCervical cancer Cytology Human papillomavirus (HPV) Screening Dual immunostaining
We are grateful to Elena Almudévar, Rosa Guarch and Oscar Manzanilla for their advisory and for taking the last look at the manuscript. We also thank the technicians of the Pathology Department at “Complejo Hospitalario de Navarra” for their valuable contribution to this study.
Compliance with ethical standards
This manuscript complies with local ethics guidelines.
Conflict of interest
The authors declare that they have no conflicts of interest.
F. Mallor partially supported by MTM2016-77015-R (AEI, FEDER, UE).
I. Paniello partially supported by MTM2017-83506-C2-1-P.
The other authors made no disclosures.
Ethical responsibilities of author section
ACC and SMM designed the study and contributed substantially with the acquisition and interpretation of data. MGM collected the data. PAI and MGF did the data analysis. ACC wrote the manuscript. LEM and CIA contributed substantially with the interpretation of data for the work. All authors contributed revising the work critically for important intellectual content and final approval of the version to be published.
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