The use of biomarkers and HPV genotyping to improve diagnostic accuracy in women with a transformation zone type 3

Manley, Kristyn; Patel, Amit; Pawade, Joya; Glew, Susan; Hunt, Katherine; Villeneuve, Nichole; Mukonoweshuro, Pinias; Thompson, Samantha; Hoskins, Helen; López-Bernal, Andres; Wills, Andrew K

doi:10.1038/s41416-021-01539-y

Cited by 8 publications

(10 citation statements)

References 36 publications

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“…A recent study suggested that the use of biomarkers and HPV genotyping could improve diagnostic accuracy for women with TZ3 lesions [ 13 ]. However, these findings are based on rather limited data.…”

Section: Introductionmentioning

confidence: 99%

Improving colposcopic accuracy for cervical precancer detection: a retrospective multicenter study in China

et al. 2022

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Background Colposcopy alone can result in misidentification of high-grade squamous intraepithelial or worse lesions (HSIL +), especially for women with Type 3 transformation zone (TZ) lesions, where colposcopic assessment is particularly imprecise. This study aimed to improve HSIL + case identification by supplementing referral screening results to colposcopic findings. Methods This is an observational multicenter study of 2,417 women, referred to colposcopy after receiving cervical cancer screening results. Logistic regression analysis was conducted under uni- and multivariate models to identify factors which could be used to improve HSIL + case identification. Histological diagnosis was established as the gold standard and is used to assess accuracy, sensitivity, and specificity, as well as to incrementally improve colposcopy. Results Multivariate analysis highlighted age, TZ types, referral screening, and colposcopists’ skills as independent factors. Across this sample population, diagnostic accuracies for detecting HSIL + increased from 72.9% (95%CI 71.1–74.7%) for colposcopy alone to 82.1% (95%CI 80.6–83.6%) after supplementing colposcopy with screening results. A significant increase in colposcopic accuracy was observed across all subgroups. Although, the highest increase was observed in women with a TZ3 lesion, and for those diagnosed by junior colposcopists. Conclusion It appears possible to supplement colposcopic examinations with screening results to improve HSIL + detection, especially for women with TZ3 lesions. It may also be possible to improve junior colposcopists’ diagnoses although, further psychological research is necessary. We need to understand how levels of uncertainty influence diagnostic decisions and what the concept of “experience” actually is and what it means for colposcopic practice.

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Section: Introductionmentioning

confidence: 99%

Improving colposcopic accuracy for cervical precancer detection: a retrospective multicenter study in China

et al. 2022

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“…Packet et al reported a sensitivity and NPV for DS of 95% and 94%, respectively, in a subgroup of women with inconclusive colposcopy (due to bleeding, inflammation or incomplete visualisation of the TZ) 29 . A recent study investigated the use of DS in HPV‐positive women with low‐grade cytology and TZ3 undergoing LLETZ and reported a sensitivity of 100% and NPV of 100% of DS for CIN2+ detection, whereas the specificity and PPV were 73.8% and 76.1%, respectively 31 . These findings are in line with our results although there are important differences in the median age (68 years in our study versus 39 years in the study by Manley et al) 31 .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study investigated the use of DS in HPV‐positive women with low‐grade cytology and TZ3 undergoing LLETZ and reported a sensitivity of 100% and NPV of 100% of DS for CIN2+ detection, whereas the specificity and PPV were 73.8% and 76.1%, respectively 31 . These findings are in line with our results although there are important differences in the median age (68 years in our study versus 39 years in the study by Manley et al) 31 . To our knowledge, only one study has reported the performance of DS in postmenopausal women 32 .…”

Section: Discussionmentioning

confidence: 99%

“…A recent study 31 found DS of cervical cytology samples from HPV‐positive women with low‐grade cytology to have superior sensitivity, NPV and PPV for CIN2+ detection compared with ECC. However, as the mean age was 39 years, the value of ECC may not be fully comparable to an older postmenopausal population 31 . Another practice in the diagnostic work‐up in postmenopausal women referred because of abnormal screening results and who have a TZ3 is a diagnostic LLETZ 5–7 .…”

Section: Discussionmentioning

confidence: 99%

“…HPV DNA testing was performed using the clinically validated Cobas 4800 HPV DNA test (Roche Diagnostic) according to the manufacturer's instructions. This assay enables individual detection of HPV 16 and HPV 18, and pooled detection of 12 other high-risk HPV types (31,33,35,39,45,51,52,56,58,59, 66 and 68). 20 DS was performed using the residual SurePath cell pellet in all included women regardless of HPV result.…”

Section: Cytology Hpv and P16/ki67 Dual Stainmentioning

confidence: 99%

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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

Gustafson

Tranberg

Christensen

et al. 2022

BJOG

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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.

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Validation of an on-chip p16ink4a/Ki-67 dual immunostaining cervical cytology system using microfluidic device technology

Hashimoto,

Kumagai,

Nomura

et al. 2023

Sci Rep

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More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

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The use of biomarkers and HPV genotyping to improve diagnostic accuracy in women with a transformation zone type 3

Cited by 8 publications

References 36 publications

Improving colposcopic accuracy for cervical precancer detection: a retrospective multicenter study in China

Improving colposcopic accuracy for cervical precancer detection: a retrospective multicenter study in China

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

Validation of an on-chip p16ink4a/Ki-67 dual immunostaining cervical cytology system using microfluidic device technology

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