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Adjunctive testing by cytology, p16/Ki‐67 dual‐stained cytology or HPV16/18 E6 oncoprotein for the management of HPV16/18 screen‐positive women
Author(s) -
TorresIbarra Leticia,
Lorincz Attila T.,
Wheeler Cosette M.,
Cuzick Jack,
HernándezLópez Rubí,
Spiegelman Donna,
LeónMaldonado Leith,
RiveraParedez Berenice,
MéndezHernández Pablo,
LazcanoPonce Eduardo,
Salmerón Jorge
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33414
Subject(s) - colposcopy , cytology , medicine , genotyping , cervical cancer , cervical intraepithelial neoplasia , triage , gynecology , cervical cancer screening , cancer , oncology , gastroenterology , obstetrics , pathology , genotype , biology , emergency medicine , biochemistry , gene
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+.