Diagnostic value of p16INK4A, Ki‐67, and human papillomavirus L1 capsid protein immunochemical staining on cell blocks from residual liquid‐based gynecologic cytology specimens

Abstract

BACKGROUND: This study was conducted to evaluate the reliability and role of cell block preparations in the diagnosis of neoplastic and preneoplastic lesions of the cervix and to improve the value of cell block preparations in diagnosing and predicting the prognosis of cervical lesions through immunostaining of p16INK4A (p16), Ki-67, and human papillomavirus (HPV) L1 capsid protein (HPV L1). METHODS: In total, 138 specimens were diagnosed on liquid-based cytology (LBC) and cell block preparations, and 63 specimens were subjected subsequently to tissue follow-up and immunostaining for p16, Ki-67, and HPV L1 on cell block sections. RESULTS: In 42 specimens that were diagnosed as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) on cell blocks, 38 specimens (90.5%) were confirmed by histopathologic reports, and there was slightly better than 81.6% agreement between LBC and tissue follow-up. Immunointensity and cells that were positive for p16 were enhanced according to increased pathologic grade and differed statistically between cervical intraepithelial neoplasia 1 (CIN-1) and CIN-2/CIN-3 as well as SCC. The positive rates of HPV L1 decreased gradually according to the severity of cervical neoplasia, and HPV L1/p16 expression patterns were related to the severity of cervical lesions. CONCLUSIONS: The cell block preparation technique was complementary to LBC, and the authors concluded that the application of LBC combined with cell block preparations may improve the diagnostic accuracy of cytology. Immunostaining for p16 and Ki-67 on cell block preparations can help to improve the diagnostic accuracy of HSIL and SCC. A combined expression pattern of p16 and HPV L1 may serve as a valuable index for predicting prognosis and follow-up of cervical dysplastic lesions. Cancer (Cancer Cytopathol) 2010;118:47-55.

Combination of p16INK4a/Ki67 immunocytology and hpv polymerase chain reaction for the noninvasive analysis of HPV involvement in head and neck cancer

“…21,22 However, it is still hard to distinguish between a latent HPV infection with the potential of self-limitation and a transforming infection leading to the development of cervical neoplasia. 23 Therefore, recent studies proposed simultaneous immunocytochemical detection of p16 INK4a as a biomarker associated with high-risk HPV infection and Ki67 as a marker of a high cell proliferation rate, 24 …”

Relationship of HPVL1 and p16 expression with different cervical lesions

“…Similarly, in histology only 2% of normal biopsies and 38% of CIN I showed diffuse staining for p16INK4a compared to 68% of CIN II and 82% of CIN III (Tsoumpou et al, 2009). In addition, the immunointensity and cells that were positive for p16 were enhanced according to increased pathologic grade and differed statistically between CIN-I and CIN-II/CIN-III as well as SCC (Yu et al, 2010). Our results revealed the p16 expression increased with the increase of the grade of cervical lesions.…”

“…Compared with p16 alone, the combination with L1 may be particularly useful in assessing those lesions that are still in the productive phase of carcinogenesis. Yu et al (2010) also noted HPVL1/p16 expression patterns were related to the severity of cervical lesions. Yoshida et al (2008) performed liquid-based cytology in 63 patients and found that the detection rate of P16(-)/L1(+) in LSIL, HSIL and SCC was 44, 0 and 0%, respectively, and that of P16(+)/L1(-) was 82, 88 and 100%, respectively.…”

“…In 71 ASCUS/LSIL without treatment, no L1-positive cases progressed in cytology; 18.75% of L1-negative cases progressed to ASC-H/HSIL (Xiao et al, 2010). In addition, the positive rates of HPVL1 decreased gradually according to the severity of cervical neoplasia (Yu et al, 2010).…”

Human Papillomavirus and Related Diseases - From Bench to Bedside - A Clinical Perspective

“…p16 in conjunction with Ki-67 provide high sensitivity for the detection of CIN2+ lesions (Schmidt et al, 2011;Yu et al, 2010).…”