The Diagnostic Utility of p16 Immunostaining in Differentiating Cancer and HSIL from LSIL and Benign in Cervical Cells

Abstract

Cervical liquid-based cytology plays an important role in the diagnosis of cervical squamous intraepithelial lesion (SIL). However, cytological evaluation alone has a relatively low sensitive. To overcome this problem, HPV DNA testing or HPV DNA combined with cytology has been applied. HPV DNA testing significantly improved the sensitivity, but the specificity is low, especially in cancer and high-grade SIL (HSIL) cases. The aim of this study was to evaluate the diagnostic utility of p16 overexpression in cervical cells of patients with HSIL and cancer. The expression of p16 was detected by immunostaining in liquid-based cells from cervical brushing in 278 patients which including: Cancer (n = 13), HSIL (n = 112), low-grade SIL (LSIL) (n = 45), and Benign (n = 108). The expression levels of p16 were significantly higher in the cancer and HSIL groups when compared with the LSIL and Benign groups (P < 0.01). The accurate diagnostic rates of cancer and HSIL were significantly increased by p16 immunostaining plus cytology than that by cytology alone (P < 0.01). The false negative or false positive of p16 immunostaining occurred with a unicellular pattern. With sensitivity of 96.0% and accuracy of 91.7%, the diagnostic performance of p16 immunostaining was much better than that of cytology alone with sensitivity of 36.0% and accuracy of 70.9% (P < 0.01). p16 immunostaining in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia but also help to distinguish HSIL from LSIL and the triage of transient infection.

Absence of Nuclear p16 Is a Diagnostic and Independent Prognostic Biomarker in Squamous Cell Carcinoma of the Cervix

“…We confirmed p16 overexpression in our series of 78 cervical tumors, as extensively described [3,14,16,21], since strong p16 expression is a proven useful surrogate biomarker for tumors with transcriptionally active HR-HPV [5]. Importantly, we found that p16 expression-and especially the cytoplasmic/nuclear p16 ratio-significantly distinguished HSIL from SCCC.…”

“…Our findings are therefore evidence of the usefulness of p16 as a diagnostic biomarker between HSIL and SCCC, as previously proposed [18,19]. In fact, it has facilitated inter-observer agreement and then has improved the accuracy of traditional diagnostic methods based on histological observation in lower grade lesions [4][5][6]21,30].…”

“…In spite of these well-recognized tumor-suppressor properties, p16 expression paradoxically increases with the severity of the cervical lesion [3,5,14,16], and has been then proposed as a useful marker for identifying such lesions [5,[17][18][19][20]. In fact, its ancillary use in cervical cytology has improved the accuracy of histological diagnosis [5,21], mainly in premalignant lesions [4]. However, the specificity of p16 has been insufficiently studied in SCCC [18], and its prognostic value remains controversial [3,5,14].…”

Expression of P16 biomarker in squamous cell carcinoma of uterine cervix and its association with clinico-pathological parameters: A cross-sectional study

“…In conditions of inhibition / low P16 expression, there will be high expression of cancer stem cells which results in increased ability of self-renewal of cancer stem cells 16 . The sensitivity, specificity and accuracy of P16 biomarker to diagnose SCC of cervix is 96.0%, 88.2% and 91.7%, respectively 17 .…”

Squamous Intraepithelial Cervix Lesions: Possible Early Diagnostics and Management

“…Следовательно, функциональная инактивация pRB приводит к рефлекторной активации p16, экспрессия которого в низких концентрациях наблюдается в здоровых клетках, в то время как при HSIL и РШМ наблюдается гиперэкспрессия p16. Данный феномен используется в качестве надежного индикатора персистенции высокоонкогенных типов ВПЧ [21].…”