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Archives of Gynecology and Obstetrics

, Volume 299, Issue 1, pp 141–149 | Cite as

Human papillomavirus DNA, HPV L1 capsid protein and p16INK4a protein as markers to predict cervical lesion progression

  • Huiyan Hu
  • Jingjing Zhao
  • Wen Yu
  • Junwei Zhao
  • Zhewei Wang
  • Lin Jin
  • Yunyun Yu
  • Lingfei Han
  • Lu Wang
  • Huiting ZhuEmail author
  • Fang LiEmail author
General Gynecology
  • 112 Downloads

Abstract

Objectives

Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments.

Methods

1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16.

Results

HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p < 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value < 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value < 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(−) p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value < 0.005). Furthermore, patients with L1(−) p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(−) p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(−) p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value < 0.005) (Table 6).

Conclusion

With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination.

Keywords

HPV DNA HPV L1 capsid protein p16 LSIL HSIL 

Abbreviations

CIN

Cervical intraepithelial neoplasia

CC

Chronic cervicitis

LSIL

Low-grade squamous intraepithelial lesion

HSIL

High-grade squamous intraepithelial lesion

SCC

Squamous cell carcinoma

HPV

Human papilloma virus

IHC

Immunohistochemistry

Notes

Acknowledgements

This work was supported by Shanghai Science and Technology Committee Foundation (Grant no. 15411967700, 16411950200), National Natural Science Foundation of China (Grant no. 81771529), and Shanghai Natural Science Foundation (Grant no. 15ZR1433300).

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gynaecology, Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghaiChina
  2. 2.Clinical Pathology, Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghaiChina

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