Gothwal Meenakshi, Nalwa Aasma, Singh Pratibha, Yadav Garima, Bhati Meenal, Samriya Nitesh
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (AIIMS), Jodhpur, Jodhpur, Rajasthan 342005 India.
Department of Pathology, AIIMS Jodhpur, Jodhpur, Rajasthan 342005 India.
J Obstet Gynaecol India. 2021 Feb;71(1):72-77. doi: 10.1007/s13224-020-01380-y. Epub 2020 Nov 18.
Cervical cancer is the most common cancer in India. Screening for cervical cancer helps in marked reduction of invasive cervical cancers. The low sensitivity of Papanicolaou cytology (Pap smear) and high-risk human papillomavirus (HR-HPV) in excluding high-grade intraepithelial lesion (ASC-H) leads to unnecessary referrals to colposcopy-guided biopsy. The combined cervical cytology screening and HR-HPV have its own limitations and still need further standardization. Using additional biomarkers like staining with p16 and Ki-67 might help in triaging abnormal pap smear.
A prospective, cross-sectional study was performed over a period of 16 months in the Department of Obstetrics and Gynaecology, in collaboration with Department of Pathology. Study was conducted to know the efficacy of immunostaining with p16/Ki-67 in predicting the presence of significant lesion in cases of mild cytological atypia. PAP smears (conventional and LBC) along with P16, Ki-67 and available biopsies were correlated.
Liquid-based cytology (LBC) was done in 2134 cases, out of which 46 cases showed abnormal cytological findings such as [22 atypical squamous cells of undetermined significance (ASCUS), 3 low-grade squamous intraepithelial lesion (LSIL), 8 atypical squamous cells cannot exclude high-grade lesion (ASC-H), 6 high-grade squamous intraepithelial lesion (HSIL), 5 squamous cell carcinoma (SCC), 2 adenocarcinoma, 1 atypical glandular cells of undetermined significance (AGUS)]. Immunostaining with p16 and Ki-67 was performed on 38 cases of abnormal cytological smears. Out of 38 abnormal cytology cases, 28 cases had shown co-staining for both p16 and Ki-67, suggestive of true HPV infection of the cells. Of the 38 cases, 07/14 ASCUS, 06/06 HSIL, 07/08 ASC-H, 05/05 squamous cell carcinoma and 02/02 adenocarcinoma also showed dual positivity for p16 and Ki-67. One case of AGUS was diagnosed, but the smear was unsatisfactory for immunocytochemical evaluation and excluded from the study. Three cases of LSIL were also diagnosed on cytological evaluation, and 1 of them however showed positivity for p16 and Ki-67 on immunocytochemistry (ICC). In the ASC-US group, the sensitivity and specificity of the immunostaining in diagnosing CIN2 + lesions were 87.51%, and in LSIL group, the sensitivity and specificity of the immunostaining in diagnosing CIN2 + lesions were 100%. p16/Ki-67 positivity also increased with cytological severity which in turn corresponded with histological findings: it reached from 50% in ASC-US to 100% in both HSIL and SCC categories.
This immunostaining with p16 and Ki67 can be a useful method in the triaging of the ASC-US and the LSIL group as considering the high sensitivity and specificity values.
宫颈癌是印度最常见的癌症。宫颈癌筛查有助于显著降低浸润性宫颈癌的发病率。巴氏细胞学检查（巴氏涂片）和高危型人乳头瘤病毒（HR-HPV）在排除高级别上皮内病变（ASC-H）方面敏感性较低，导致不必要的阴道镜引导下活检转诊。联合宫颈细胞学筛查和HR-HPV有其自身的局限性，仍需进一步标准化。使用诸如p16和Ki-67染色等额外的生物标志物可能有助于对异常巴氏涂片进行分流。
在妇产科与病理科合作开展了一项为期16个月的前瞻性横断面研究。进行该研究以了解p16/Ki-67免疫染色在预测轻度细胞学非典型病例中显著病变存在情况的有效性。将传统巴氏涂片和液基薄层细胞学（LBC）涂片与P16、Ki-67及可用活检结果进行关联分析。
共对2134例进行了液基细胞学检查，其中46例显示异常细胞学结果，如[22例意义不明确的非典型鳞状细胞（ASCUS）、3例低级别鳞状上皮内病变（LSIL）、8例非典型鳞状细胞不能排除高级别病变（ASC-H）、6例高级别鳞状上皮内病变（HSIL）、5例鳞状细胞癌（SCC）、2例腺癌、1例意义不明确的非典型腺细胞（AGUS）]。对38例异常细胞学涂片进行了p16和Ki-67免疫染色。在38例异常细胞学病例中，28例p16和Ki-67均呈共染色，提示细胞存在真正的HPV感染。在38例病例中，07/14 ASCUS、06/06 HSIL及07/08 ASC-H、05/05鳞状细胞癌和02/02腺癌p16和Ki-67也呈双阳性。诊断出1例AGUS，但涂片不适合免疫细胞化学评估，被排除在研究之外。细胞学评估诊断出3例LSIL，其中1例免疫细胞化学（ICC）显示p16和Ki-67阳性。在ASC-US组中，免疫染色诊断CIN2+病变的敏感性和特异性分别为87.51%，在LSIL组中，免疫染色诊断CIN2+病变的敏感性和特异性均为100%。p16/Ki-67阳性也随细胞学严重程度增加，这反过来与组织学结果相对应：从ASC-US中的50%升至HSIL和SCC类别中的100%。
考虑到高敏感性和特异性值，p16和Ki67免疫染色可作为ASC-US和LSIL组分流的有用方法。
