Adjunctive testing by cytology, p16/Ki-67 dual-stained cytology or HPV16/18 E6 oncoprotein for the management of HPV16/18 screen-positive women

Leticia Torres-Ibarra, Attila T Lorincz, Cosette M Wheeler, Jack Cuzick, Rubí Hernández-López, Donna Spiegelman, Leith León-Maldonado, Berenice Rivera-Paredez, Pablo Méndez-Hernández, Eduardo Lazcano-Ponce, Jorge Salmerón, Leticia Torres-Ibarra, Attila T Lorincz, Cosette M Wheeler, Jack Cuzick, Rubí Hernández-López, Donna Spiegelman, Leith León-Maldonado, Berenice Rivera-Paredez, Pablo Méndez-Hernández, Eduardo Lazcano-Ponce, Jorge Salmerón

Abstract

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 dual-stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18-positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P < .001), whereas E6 had a sensitivity of 37.8% and a specificity of 83.5%. No invasive cancer was missed by DS or E6, but 75% were in normal cytology. DS test was associated with nearly 75% reduction of colposcopy referrals compared with the direct referral of all HPV16/18-positive women, giving the least number of colposcopies (n = 4.3) per CIN3+ detected. We show that adjunctive testing of HPV16/18-positive women with DS may greatly reduce unnecessary colposcopy referrals within HPV-based screening employing HPV16/18 genotyping while retaining acceptable sensitivity for CIN2+ and CIN3+.

Trial registration: ClinicalTrials.gov NCT02510027.

Keywords: E6 oncoprotein; cervical cancer; cytology; human papillomavirus; p16/Ki-67.

© 2020 UICC.

References

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Source: PubMed

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