Efficiency of the immunocytochemical method for assessing p16 / Ki-67 coexpression in the diagnosis of cervical pathology

Background. Cervical intraepithelial lesion with human papillomavirus (HPV) is one of the most common HPV-associated diseases. In recent years, immunocytochemical detection of p16 / Ki-67 coexpression has been considered as an additional method for confirming precancerous and cancerous cervical lesions, with high sensitivity and specificity.

Aim. To determine the detection rate of p16 / Ki-67 coexpression depending on the degree of intraepithelial lesion, human papillomavirus genotype, viral load, and the presence of coinfection. To calculate the performance indicators of the immunocytochemical method and the polymerase chain reaction method for detecting HPV DNA for the diagnosis of severe intraepithelial lesions and cervical carcinoma (cervical intraepithelial neoplasia, CIN 2+).

Materials and methods. The study included material from 129 patients. Depending on the degree of cervical lesion, the following groups were formed: low-grade squamous intraepithelial lesion (CIN 1), high-grade squamous intraepithelial lesion (2–3), carcinoma. The comparison groups included patients without intraepithelial changes and with negative / positive results for HPV DNA. Coexpression of p16 / Ki-67 was assessed using immunocytochemistry, HPV DNA was determined by real-time polymerase chain reaction. The results were evaluated in comparison with histology. Results. The frequency of detection of positive p16 / Ki-67 immunocytochemistry depending on the degree of dysplasia and carcinoma of the cervix: CIN 1 – 26.5 % (n = 9), CIN 2 – 59.3 % (n = 16), CIN 3 – 88.2 % (n = 15), squamous cell carcinoma – 88.9 % (n = 8). Co-expression was more often detected in the presence of HPV infection of genotypes 16, 18 and 31. The median viral load was higher in the presence of double staining p16 / Ki-67 and amounted to 6.21 lg, in the absence of coexpression – 5.02 lg. No statistically significant differences were found in the frequency of detection of co-expression of p16 / Ki-67 depending on the number of HPV genotypes in the material. The efficiency indicators of the method for diagnosing CIN 2+ were: sensitivity 73.58 %, specificity 82.35 %.

Conclusion. A positive coexpression of p16 / Ki-67 is more often detected in severe intraepithelial lesions of the cervix and the presence of HPV genotypes 16, 18 and 31. Immunocytochemical method of assessing p16 / Ki-67 coexpression is more specific in the diagnosis of precancerous and cancerous diseases of the cervix compared to the detection of HPV DNA.

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