TY - JOUR
T1 - Clinical utility of p16/Ki67 dual-stain cytology for detection of cervical intraepithelial neoplasia grade two or worse in women with a transformation zone type
T2 - 3: A cross-sectional study
AU - Gustafson, Line Winther
AU - Nielsen, Mette Tranberg
AU - Christensen, Pia
AU - Brøndum, Rikke
AU - Wentzensen, Nicolas
AU - Clarke, Megan
AU - Andersen, Berit
AU - Kjeld Petersen, Lone
AU - Bor, Isil Pinar
AU - Hammer, Anne
PY - 2023/1
Y1 - 2023/1
N2 - Objective: To evaluate the clinical utility of p16/Ki67 dual-stain (DS) compared with cytology for detecting cervical intraepithelial lesion grade two or worse (CIN2+) in women with a transformation zone type 3 (TZ3). Design: Cross-sectional study. Setting: Colposcopy clinics in Central Denmark Region. Population: Women aged 45 years or older referred for colposcopy because of an abnormal screening test. Methods: All women had a cervical sample collected for cytology and DS testing and underwent large-loop excision of the transformation zone (LLETZ). Main outcome measure: Sensitivity, specificity and negative (NPV) and positive (PPV) predictive values of DS for CIN2+ detection were compared to those of cytology. Results: Of 166 women eligible, 93 (56.0%) were included in the final analysis. Median age was 68 years (interquartile range [IQR] 63.4–70.5 years). Most women were postmenopausal (95.7%) and referred based on a positive human papillomavirus screening test (86.0%). Fifty-two women (55.9%) were DS-positive, 29 (55.8%) of whom had CIN2+ detected. Twenty-seven (29.0%) women had atypical squamous cells of undetermined significance or worse (ASC-US+), and CIN2+ was detected in 21 women (77.8%). DS had a higher sensitivity (96.7% versus 70.0% p = 0.021) and NPV (97.6% versus 86.4%, p = 0.018) compared with cytology for CIN2+ detection. In contrast, the specificity (63.5% versus 90.5% p < 0.001) and PPV (55.8% versus 77.8%, p = 0.001) were lower for DS compared with cytology. Conclusions: Dual stain may be a valuable risk marker to guide clinical management of women with a TZ3. The superior NPV of DS suggests that a diagnostic excision may safely be avoided in DS-negative women.
AB - Objective: To evaluate the clinical utility of p16/Ki67 dual-stain (DS) compared with cytology for detecting cervical intraepithelial lesion grade two or worse (CIN2+) in women with a transformation zone type 3 (TZ3). Design: Cross-sectional study. Setting: Colposcopy clinics in Central Denmark Region. Population: Women aged 45 years or older referred for colposcopy because of an abnormal screening test. Methods: All women had a cervical sample collected for cytology and DS testing and underwent large-loop excision of the transformation zone (LLETZ). Main outcome measure: Sensitivity, specificity and negative (NPV) and positive (PPV) predictive values of DS for CIN2+ detection were compared to those of cytology. Results: Of 166 women eligible, 93 (56.0%) were included in the final analysis. Median age was 68 years (interquartile range [IQR] 63.4–70.5 years). Most women were postmenopausal (95.7%) and referred based on a positive human papillomavirus screening test (86.0%). Fifty-two women (55.9%) were DS-positive, 29 (55.8%) of whom had CIN2+ detected. Twenty-seven (29.0%) women had atypical squamous cells of undetermined significance or worse (ASC-US+), and CIN2+ was detected in 21 women (77.8%). DS had a higher sensitivity (96.7% versus 70.0% p = 0.021) and NPV (97.6% versus 86.4%, p = 0.018) compared with cytology for CIN2+ detection. In contrast, the specificity (63.5% versus 90.5% p < 0.001) and PPV (55.8% versus 77.8%, p = 0.001) were lower for DS compared with cytology. Conclusions: Dual stain may be a valuable risk marker to guide clinical management of women with a TZ3. The superior NPV of DS suggests that a diagnostic excision may safely be avoided in DS-negative women.
KW - cervical intraepithelial neoplasia
KW - colposcopy
KW - human papillomavirus
KW - large-loop excision of the transformation zone
KW - liquid-based cytology
KW - p16/Ki67 dual-stain cytology
KW - postmenopausal
KW - transformation zone type 3
KW - Uterine Cervical Neoplasms
KW - Colposcopy
KW - Cross-Sectional Studies
KW - Coloring Agents
KW - Humans
KW - Middle Aged
KW - Vaginal Smears
KW - Papillomavirus Infections
KW - Uterine Cervical Dysplasia/pathology
KW - Female
KW - Papillomaviridae
KW - Aged
KW - Cyclin-Dependent Kinase Inhibitor p16/analysis
KW - Ki-67 Antigen/analysis
U2 - 10.1111/1471-0528.17248
DO - 10.1111/1471-0528.17248
M3 - Journal article
C2 - 35686564
SN - 1470-0328
VL - 130
SP - 202
EP - 209
JO - B J O G
JF - B J O G
IS - 2
ER -