The p16/ki-67 assay is a safe, effective and rapid approach to triage women with mild cervical lesions

Abstract

Objective The aim of this study was to evaluate the diagnostic accuracy and efficiency of p16/ki-67 dual stain in the identification of CIN2+ lesions, in Greek women with ASCUS or LSIL cytology. Methods A total of 200 women, 20 to 60 years old, were enrolled in the study. All samples were cytologically evaluated and performed for p16/ki-67 and high-risk HPV (HR-HPV) test. All patients were referred to colposcopy for biopsy and histological evaluation. Three cervical cancer (CC) screening strategies were designed and the total direct medical costs of the procedures during our clinical trial were evaluated, from a healthcare perspective. Results HPV 16 as expected was the most common HR-HPV type followed by HPV 31 and HPV 51. The risk for CIN2+ was significantly higher in HPV 16/18 positive cases. p16/ki-67 demonstrated a high sensitivity for CIN2+ identification in both ASCUS and LSIL groups (90.4% and 95%, respectively). HR-HPV test with sensitivity 52.3% and 65.5%, as well as colposcopy with sensitivity 14.3% and 36% respectively in ASCUS and LSIL group, showed inferior results compared to p16/ki-67. The specificity of p16/ki-67 for ASCUS and LSIL was 97.2% and 95.2% respectively, inferior only to colposcopy: 100% and 100%, lacking however statistical significance. HR-HPV test instead, presented the lowest specificity: 76.4% and 71.4% respectively in comparison to the other two methods. From a healthcare perspective, the costs and benefits of the tests implementation for the annual screening and triaging, in three CC screening strategies, were also calculated and discussed. Conclusions The results of the study indicate that p16/ki-67 is a safe and rapid assay that could be used to detect CIN2+ among women with mild cervical lesions, presenting both high sensitivity and specificity and could minimize the psychological and economic burden of HPV screening.

Correlation between high‐risk HPV infection and p16/Ki‐67 abnormalities in Pap samples in a South Eastern Europe cohort

“…A recent study of Beyzit et al found HPV58 to be the most abundant HPV type in their sample pool, second to HPV16 18 . Additionally, a study in a Greek female population found HPV31 to be the second most abundant HPV type, following HPV16 19 . In addition, a global geographical distribution analysis of HPV associated CC cases showed various distribution of different HPV types.…”

“…The positive expression for p16/Ki-67 has proven to be extremely important in triaging patients diagnosed with ASC-US/LSIL, or non-HPV16/18 hrHPV types. 19,22 Despite strong evidence, only 10% of patients (216 cases) had an available dual staining for p16/Ki-67, meaning that the clinician did not consider necessary and/or did not order a dual staining test.…”

Novel In Situ Hybridization Assay for Chromogenic Single-Molecule Detection of Human Papillomavirus E6/E7 mRNA

“…Because distinguishing low-grade from high-grade lesions can help avoid overtreatment, different biomarkers are being explored to better assist the grading of lesions. For example, a combination of biomarkers, such as p16 and K i -67 dual staining, could be used as an adjunctive test to improve the diagnostic accuracy of histopathology and detect CIN2+ among women with mild cervical lesions ( 18 , 19 ). Adding HPV E4 immunohistochemistry to p16 and grading the expression of these two markers helps to identify the heterogeneity of HSILs ( 20 ).…”

International experience of laboratory methods in the cervical cancer screening

“…Коэкспрессия p16 и Ki-67 в одной клетке демонстрирует дисфункцию и наблюдается только в эпителии с интраэпителиальным поражением клеток, трансформированных ВПЧ. В клетках без интраэпителиального поражения экспрессия белков p16 и Ki-67 взаимоисключающая [50].…”

“…Ряд исследований показал диагностическую эффективность теста с двойным окрашиванием p16/Ki-67 [50−52]. Двойное окрашивание p16/Ki-67, с результатами цитологии ASC-US (atypical squamous cells of undetermined significance -атипичные клетки плоского эпителия неопределенного значения) или L-SIL (low-grade squamous intraepithelial lesion -плоскоклеточное интраэпителиальное поражение низкой степени), показало аналогичную чувствительность и значительно более высокую специфичность, чем тестирование на ВПЧ при сортировке ASC-US и LSIL [50], а также у женщин с нормальным Пап-тестом, но с положительным результатом ВПЧ-тестирования [53].…”