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 3: A cross‐sectional study

Abstract

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.

Beyond P16/Ki67 dual‐stain cytology: Exploring alternative biomarkers for diagnosing cervical cancer and its precursors

“…Dear Dr. Papageorghiou, With interest, we read the letter to the editor entitled: 'Beyond P16/Ki67 dual-stain cytology: exploring alternative biomarkers for diagnosing cervical cancer and its precursors' by Shah Hussain and colleagues. 1 We thank the authors for their interest in our article.…”

“…Beyond P16/Ki67 dual-stain cytology: Exploring alternative biomarkers for diagnosing cervical cancer and its precursors Dear Dr. Papageorghiou, We read with interest the article '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 3: a cross-sectional study' by Gustafson et al 1 We appreciate the authors' emphasis on the clinical utility of p16/Ki67 dual-stain cytology and would like to offer some addition war insights.…”

Authors' reply

“…In our article '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 3: a cross-sectional study', 2 we found that, compared with cytology, the p16/Ki67 dual stain had superior sensitivity and negative predictive value for detecting cervical intraepithelial neoplasia grade two or worse (CIN2+) in women with a transformation zone type 3 (TZ3) at colposcopy. We demonstrated that p16/Ki67 dual stain could be a valuable risk marker to guide clinical management in a group of women with abnormal screening results where colposcopy is very challenging.…”

“…Line Winther Gustafson 1,2 Mette Tranberg 1 Pia Nørgaard Christensen 3 Rikke Brøndum 3 Nicolas Wentzensen 4 Megan A. Clarke 4 Berit Andersen 1,5 Lone Kjeld Petersen 6,7 Pinar Bor 5,8 Anne Hammer 5,9…”

HPV Testing and its Role in Cervical Cancer Screening

“…Clinical guidelines for use of dual stain in cervical cancer screening programs are currently in development. Several studies have demonstrated that p16 and p16/Ki-67 dual stain cytology have shown greater accuracy for the detection of cervical precancers compared with cervical cytology, [140][141][142][143][144][145][146] with evidence suggesting that a negative dual stain result provides longer reassurance against the risk of cervical precancer than negative cytology. 147 It has been demonstrated that the dual stain assay can be implemented with little training and that it is highly reproducible; 145,148,149 however, like cytology, dual stain testing requires specialized infrastructure and expertise for the interpretation of stained slides.…”