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HR-HPV viral load quality detection provide more accurate prediction for residual lesions after treatment: a prospective cohort study in patients with high-grade squamous lesions or worse

Medical Oncology volume 37, Article number: 37 (2020) Cite this article

Abstract

The relationship between high-risk-human-papillomavirus (HR-HPV) viral loads and residual/recurrence lesion is uncertain. This study aimed to evaluate the clinical value of HR-HPV viral loads to predict the residual/recurrence lesions among women with high-grade squamous lesions or worse (≥ HSIL) after surgery. Finally, 301 women who underwent primary screening of cervical cancer using polymerase-chain-reaction-(PCR)-reverse-dot-blot-(RDB) human papillomavirus (HPV) genotyping and cytology assays were enrolled. They received surgery and took HR-HPV viral loads with a BioPerfectus Multiplex Real-Time PCR assay. Colposcopy biopsies were performed in patients with HPV-16/18(+) and/or TCT ≥ ASCUS with HR-HPV(+). The risk of HR-HPV viral loads and potentials factors for residual/recurrence lesions were analyzed and the optimal cut-off values of HR-HPV viral loads were calculated. The significant differences were found in residual/recurrence lesions among patients with different ages, margin status, cytology and HR-HPV at 6 months (all P < 0.05). Interestingly, HPV viral loads were observed significant differences in the group of residual lesions, not recurrence group. Furthermore, except for HPV-31/33, the viral loads of HP-16/52/58 were significant differences in residual lesions. The cut-off level of HR-HPV viral loads was 5.22 copies/10,000 cells, providing viable triage for the risk of residual lesions. Compared with different follow-up methods, the HR-HPV viral loads ≥ 5.22copies/10,000 cells (HR 3.39, 95% CI 1.57–7.35) had a higher risk for developing residual lesions. HR-HPV viral loads can be a reliable predictor of residual lesions. Furthermore, women with viral loads ≥ 5.22 copies/10,000 cells may have higher risk for residual disease and should be give a more aggressive treatment and follow-up strategy.

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References

  1. Globocan. Cervical Cancer estimated incidence, mortality and prevalence worldwide in 2012. Available from: https://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp.

  2. Torre LA, Bray F, Siegel RL, et al. (2012) Global cancer statistics. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chen W, Zheng R, Baade PD, et al. (2015) Cancer statistics in China. CA Cancer J Clin. 2016;66(2):115–32.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Massad LS, Einstein MH, Huh WK, et al. 2012 ASCCP Consensus Guidelines Conference 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829–46.

    Article  PubMed  Google Scholar 

  5. Soutter WP, Sasieni P, Panoskaltsis T. Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia. Int J Cancer. 2006;118(8):2048–55.

    CAS  Article  PubMed  Google Scholar 

  6. Cairns M, Tidy J, Cruickshank ME. Management of microinvasive cervical cancer: a British Society for Colposcopy and Cervical Pathology audit. J Low Genit Tract Dis. 2012;16(4):403–8.

    Article  PubMed  Google Scholar 

  7. Colposcopy and Programme Management: addendum to NHSCSP Publication No 20 exceptions applicable in NHS Scotland (2013). 2nd ed: NHS Scotland.

  8. Tidy J. NHSCSP Colposcopy and Programme Management. 3rd ed. London: Public Health England; 2016.

    Google Scholar 

  9. Origoni M, Cristoforoni P, Costa S, et al. HPV-DNA testing for cervical cancer precursors: from evidence to clinical practice. Ecancermedicalscience. 2012;6:258.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sehnal B, Cibula D, Slama J. Factors influencing decisions about surgical treatment of cervical precancerous lesions. Expert Rev Anticancer Ther. 2014;14(4):441–51.

    CAS  Article  PubMed  Google Scholar 

  11. Segondy M, Ngou J, Kelly H, et al. Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV. J Clin Virol. 2018;99–100:79–83.

    Article  CAS  PubMed  Google Scholar 

  12. Wu Z, Qin Y, Yu L, et al. Association between human papillomavirus (HPV) 16, HPV18, and other HR-HPV viral load and the histological classification of cervical lesions: Results from a large-scale cross-sectional study. J Med Virol. 2017;89(3):535–41.

    CAS  Article  PubMed  Google Scholar 

  13. Sundstrom K, Ploner A, Dahlstrom LA, et al. Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(1):150–8.

    Article  CAS  PubMed  Google Scholar 

  14. Xi LF, Koutsky LA, Castle PE, et al. Human papillomavirus type 18 DNA load and 2-year cumulative diagnoses of cervical intraepithelial neoplasia grades 2–3. J Natl Cancer Inst. 2009;101(3):153–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Constandinou-Williams C, Collins SI, Roberts S, et al. Is human papillomavirus viral load a clinically useful predictive marker? A longitudinal study. Cancer Epidemiol Biomarkers Prev. 2010;19(3):832–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Dong B, Sun P, Ruan G, et al. Type-specific high-risk human papillomavirus viral load as a viable triage indicator for high-grade squamous intraepithelial lesion: a nested case- control study. Cancer Manag Res. 2018;10:4839–51.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Arbyn M, Redman CWE, Verdoodt F, et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol. 2017;18(12):1665–799.

    Article  PubMed  Google Scholar 

  18. Kim YT, Lee JM, Hur SY, et al. Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia. Int J Cancer. 2010;126(8):1903–9.

    CAS  Article  PubMed  Google Scholar 

  19. Song SH, Lee JK, Oh MJ, et al. Persistent HPV infection after conization in patients with negative margins. Gynecol Oncol. 2006;101(3):418–22.

    Article  PubMed  Google Scholar 

  20. Verma I, Jain V, Kaur T. Application of bethesda system for cervical cytology in unhealthy cervix. J Clin Diagn Res. 2014;8(9):26–30.

    Google Scholar 

  21. Sun P, Song Y, Ruan G, et al. Clinical validation of the PCR-reverse dot blot human papillomavirus genotyping test in cervical lesions from Chinese women in the Fujian province: a hospital-based population study. J Gynecol Oncol. 2017;28(5):e50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Reich O, Regauer S, Marth C, et al. Precancerous lesions of the cervix, vulva and vagina according to the 2014 WHO classification of tumors of the female genital tract. Geburtshilfe Frauenheilkd. 2015;75(10):1018–20.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Paraskevaidis E, Kalantaridou SN, Paschopoulos M, et al. Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia. Eur J Gynaecol Oncol. 2003;24(6):541–3.

    CAS  PubMed  Google Scholar 

  24. Sherman ME, Wang SS, Tarone R, et al. Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias. Cancer Epidemiol Biomarkers Prev. 2003;12(4):372–9.

    PubMed  Google Scholar 

  25. McCredie MR, Sharples KJ, Paul C, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008;9(5):425–34.

    Article  PubMed  Google Scholar 

  26. Miller AB. Evaluation of the impact of screening for cancer of the cervix. IARC Sci Publ. 1986;76:149–60.

    Google Scholar 

  27. Kocken M, Berkhof J, van Kemenade FJ, et al. Long-term CIN3+ risk in women with abnormal cytology; role of hrHPV testing. Br J Cancer. 2012;106(5):817–25.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. van Hamont D, van Ham MA, Struik-van der Zanden PH, et al. Long-term follow-up after large-loop excision of the transformation zone: evaluation of 22 years treatment of high-grade cervical intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16(2):615–9.

    Article  PubMed  Google Scholar 

  29. Park JY, et al. Risk factors predicting residual disease in subsequent hysterectomy following conization for cervical intraepithelial neoplasia (CIN) III and microinvasive cervical cancer. Gynecol Oncol. 2007;107(1):39–44.

    Article  PubMed  Google Scholar 

  30. Tainio K, Athanasiou A, Tikkinen KAO, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018;360:k499.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kang WD, Kim SM. Human papillomavirus genotyping as a reliable prognostic marker of recurrence after loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia (CIN2-3) especially in postmenopausal women. Menopause. 2016;23(1):81–6.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Mrs Fen Lin, Ms. Yuqin Gao, Ms. Huifang Lei and Ms. Yao Tong for her excellent assistance in this work and the Fujian Province Cervical Lesions Screening Cohorts Investigators for their planning and conducting the trial and for providing the biological specimens and data to the present study. Above all, they are grateful to the patients who made this study possible.

Funding

This work was supported by grants from the Fujian Provincial Natural Science Foundation of China (Grant No. 2017J01232), and the Fujian Provincial Maternity and Children’s Hospital Technology Innovation Project (Grant No. YCXM-19–01).

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Author notes

  1. Lihua Chen, Binhua Dong, and Pengming Sun have contributed equally to this work.

Affiliations

  1. Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China

    Binhua Dong, Xiaodan Mao, Wenyu Lin, Guanyu Ruan, Yafang Kang & Pengming Sun

  2. Department of Gynecology, Fujian Provincial Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China

    Lihua Chen, Qiaoyu Zhang & Pengming Sun

Authors
  1. Lihua Chen
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  2. Binhua Dong
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  3. Qiaoyu Zhang
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  4. Xiaodan Mao
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  5. Wenyu Lin
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  6. Guanyu Ruan
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  7. Yafang Kang
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  8. Pengming Sun
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Contributions

PM Sun, LH Chen: conceptualization, LH Chen, BH Dong: methodology, LH Chen, BH Dong: software, PM Sun, BH Dong: formal analysis, LH Chen, XD Mao, QY Zhang, YQ Gao, WY Lin: investigation, LH Chen, BH Dong, BH Dong, XD Mao, QY Zhang: data curation, LH Chen: writing—original draft, PM Sun: writing—review & editing, PM Sun: funding acquisition.

Corresponding author

Correspondence to Pengming Sun.

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The study was approved by the Hospital Ethics Committee (FMCH2017J01232).

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Chen, L., Dong, B., Zhang, Q. et al. HR-HPV viral load quality detection provide more accurate prediction for residual lesions after treatment: a prospective cohort study in patients with high-grade squamous lesions or worse. Med Oncol 37, 37 (2020). https://doi.org/10.1007/s12032-020-01363-z

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  • DOI: https://doi.org/10.1007/s12032-020-01363-z

Keywords

  • Human papillomavirus
  • Viral loads
  • Cervical intraepithelial neoplasia grade 2 or worse
  • Follow-up
  • Residual or recurrence lesions