ABSTRACT
BACKGROUND: Twenty percent of women referred to colposcopy have a type 3 transformation zone-where colposcopic assessment for high-grade dysplasia (CIN2+) is not possible. This study examines the effectiveness of HPV biomarkers and genotyping in combination with techniques that sample an endocervical TZ. METHODS: A prospective diagnostic accuracy study. Women booked for large-loop excision (LLETZ) with squamous dyskaryosis, high-risk HPV and a TZ3 were recruited. Immediately prior to LLETZ samples were collected for p16/Ki-67 dual-stained cytology, HPV genotyping and H&E, p16- and Ki-67-stained endocervical curettings. RESULTS: In women with low-grade screening (n = 64), 35.9% had CIN2+; dual-stained cytology had the greatest effect on the PPV of routine screening (76.1% vs 35.9%) and perfectly predicted the absence of CIN2+. In women with a high-grade screening result (n = 37); 75.6% had CIN2+ and dual-stained curettings improved the PPV (96.5 vs 75.6%). CONCLUSIONS: With high-grade screening and a TZ3, LLETZ appears safest as three quarters have CIN2+ . Women with low-grade screening and a TZ3 have a twofold increased risk of CIN2+ when compared to women where the TZ is visible. The use of dual-stained cytology may help identify those women who can be safely offered surveillance and those who require treatment.
Subject(s)
Biomarkers, Tumor/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Genotype , Ki-67 Antigen/metabolism , Papillomaviridae/genetics , Papillomavirus Infections/complications , Uterine Cervical Dysplasia/diagnosis , Adult , Colposcopy/methods , Female , Humans , Middle Aged , Neoplasm Grading , Papillomaviridae/isolation & purification , Papillomaviridae/pathogenicity , Papillomavirus Infections/genetics , Papillomavirus Infections/metabolism , Papillomavirus Infections/virology , Prospective Studies , Vaginal Smears/methods , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/virologyABSTRACT
INTRODUCTION: Twenty percent of colposcopic assessments are inadequate due to a type 3 transformation zone (TZ3). In the absence of colposcopic or histological assessment, subsequent management is guided by the referral screening test. In the UK, routine cervical screening is completed by a Cervex-Brush alone. This study examines the effectiveness of a Cytobrush in addition to a standard Cervex-Brush when used in TZ3 assessment. METHODOLOGY: An 18-month diagnostic accuracy study in a single National Health Service (NHS) Trust. Women with a TZ3 booked for large loop excision of the transformation zone (LLETZ) with a referral cytology of high-risk HPV and squamous dyskaryosis were recruited. Immediately prior to LLETZ, a Cervex-Brush plus Cytobrush liquid-based cytology sample was taken. Presence of endocervical cells was compared. Predictability of high-grade cervical intra-epithelial neoplasia (CIN2+) was by blind standardised reporting of the LLETZ histology. RESULTS: One hundred and five women were recruited from a total eligible population of 153 cases (68.8%). Endocervical cell yield was increased with the Cervex-Brush plus Cytobrush when compared to the Cervex-Brush alone (99.1% vs 79.1%, P < .001). Irrespective of cytological grade, age or parity, there was no difference in predictability of CIN2+ between sampling methods. CONCLUSIONS: When compared to Cervex-Brush sampling alone, the addition of a Cytobrush improves endocervical sampling but does not improve cytological predictability of CIN2+ in women with a TZ3. These data suggest that women who will reliably attend for cytological follow-up can be safely referred to primary care for a Cervex-Brush alone.
