Objective  To explore the expression of human papilloma virus (HPV) L1 protein and programmed cell death ligand-1 (PD-L1) protein in cervical precancerous lesions and cervical cancer, to analyze the correlation between HPV L1 and PD-L1 expression tests combined with colposcopy and the occurrence and development of of cervical lesions, and to determine the significance of the combined examination for auxiliary differential diagnosis.

  Methods  260 patients with high-risk HPV (HR-HPV) infection who were treated at West China Second University Hospital, Sichuan University from January, 2018 to January, 2020 were included in the study. 260 cervical cytology specimens were collected, of which 218 cervical histology specimens were collected, of which 202 cases underwent colposcopy. Among the 260 cervical cytology specimens, 40 were of cervical inflammatory cells, 40 were of low-grade squamous intraepithilia lesions (LSIL) with mild atypical hyperplasia, 80 were of high-grade squamous intraepithilia lesions (HSIL) with moderate and severe atypical hyperplasia, and 100 were of cervical carcinoma cells (CCC). Among the 218 cervical histology specimens, 15 were of chronic cervicitis tissue, 20 were of cervical intraepithelial neoplasia (CIN) 1, 32 were of CIN 2, 51 were of CIN 3, and 100 were of cervical cancer (CC). Among the 260 patients, 202 underwent colposcopy. Immunocytochemistry and immunohistochemistry were used to assess the expression of HPV L1 protein and PD-L1 protein, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess the level of PD-L1 mRNA in chronic cervicitis tissues and CC. The sensitivity, specificity, positive predictive value and negative predictive value of HPV L1 and PD-L1 tests combined with colposcopy in the detection of cervical lesions were studied.

  Results  ①In the cervical cytology group, the positive rate of HPV L1 expression was 82.50%, 57.50%, 11.25%, and 3.00% in cervical inflammatory cells, low-grade squamous intraepithilia lesions (LSIL), high-grade squamous intraepithilia lesions (HSIL) and CCC, respectively, showing decreasing levels of positive expression rate (P<0.05). In the cervical histology group, the positive rate of HPV L1 expression was 86.67%, 65.00%, 34.38%, 11.76% and 4.00% in chronic cervicitis tissues, CIN 1 group, CIN 2 group, CIN 3 group and CC group, respectively, showing decreasing levels of positive expression (P<0.05). ②In the cervical cytology group, the average positive expression scores of PD-L1 in the cervical inflammatory cells, LSIL group, HSIL group, and CCC group were 0.25±0.12, 1.05±0.67, 1.39±0.11 and 2.14±0.17, respectively, showing increasing levels of positive expression scores (P<0.05). In the cervical histology group, the average positive expression scores of PD-L1 were 0.28±0.24, 1.21±0.79, 1.56±0.26, 1.80±0.24, and 2.10±0.19 in the chronic cervicitis tissue, CIN 1 group, CIN 2 group, CIN 3 group and CC group, respectively, showing increasing levels of positive expression scores (P<0.05). The relative expression of PD-L1 mRNA in chronic cervicitis tissue and CC is 1.02±0.04 and 1.81±0.22, respectively (P<0.05). ③The sensitivity and specificity of diagnosis of cervical tissue CIN2 and abovelesions, HPV L1 detection alone was 95.8%, 47.2%, PD-L1 detection alone was 96.5%, 32.8%, colposcopy alone was 77.5%, 70.8%, HPV L1/PD-L1 tests combined detection was 92.4%, 64.5%, HPV L1/PD-L1 detection combined colposcopy was 71.6% and 89.6%, respectively. The sensitivity and specificity of the HPV L1/PD-L1 combined test for the diagnosis of CIN3 and above cervical lesions were 71.9% and 86.1%, HPV L1/PD-L1 combined with colposcopy were 50.5% and 100.0%, respectively.

  Conclusion  The specificity of HPV L1/PD-L1 detection combined with colposcopy for CIN2 and above lesions is higher than that of HPV L1 detection alone, PD-L1 detection alone and colposcopy alone. HPV L1/PD-L1 detection combined with colposcopy detection for CIN3 and above lesions has an important auxiliary diagnostic value.