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HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study

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Abstract

Background

In cervical cancer screening programs, women with abnormal cytology are referred for colposcopy for histological evaluation. We examined whether a human papillomavirus (HPV) genotyping assay could be used to identify women who do not need immediate colposcopy and biopsy because of low risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+).

Methods

We prospectively evaluated test performance for 2 carcinogenic HPV genotypes (HPV16/18), for 8 types (HPV16/18/31/33/35/45/52/58), and for 13 types (HPV16/18/31/33/35/45/51/52/56/58/59/68) for prediction of histological CIN3+ results among 427 screen-positive women referred for colposcopy. The study subjects consisted of 214 women with low-grade squamous intraepithelial lesion (LSIL), 184 with high-grade squamous intraepithelial lesion (HSIL), and 29 with atypical squamous cells, cannot exclude HSIL (ASC-H).

Results

Among women with LSIL cytology, HPV16/18 positivity was 29.4 % and increased to 58.9 % for 8 types and to 74.8 % for 13 types (P < 0.001). The risk of CIN3+ biopsy results was still 7.9 % for women testing negative for HPV16/18, but decreased to 0.0 % for those testing negative for at least eight types of HPV (HPV16/18/31/33/35/45/52/58). Although HPV genotyping results enabled additional risk stratification among women with HSIL/ASC-H cytology, the risk of histological CIN3+ diagnosis among women testing negative for eight types or more was still sufficiently high (>35 %) to warrant immediate colposcopy referral.

Conclusions

Of women with LSIL cytology, those testing negative for at least eight of the highest-risk types of HPV (HPV16/18/31/33/35/45/52/58) may not need immediate colposcopy and biopsy. This would reduce the number of colposcopy referrals by approximately 40 %. However, the HPV genotyping assay is not likely to alter the clinical management of women with HSIL/ASC-H.

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References

  1. Massad LS, Einstein MH, Huh WK et al (2013) 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 121:829–846

    Article  PubMed  Google Scholar 

  2. NHS (2010) NHSCSP Publication No.20. Colposcopy and programme management: guidelines for the NHS cervical screening programme, 2nd edn. http://www.cancerscreening.nhs.uk/cervical/publications/nhscsp20.pdf. Accessed 6 Nov 2014

  3. Takeda T, Wong TF, Adachi T et al (2012) Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition. J Obstet Gynaecol Res 38:615–631

    Article  PubMed  Google Scholar 

  4. ASCUS-LSIL Traige Study (ALTS) Group (2003) A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 188:1393–1400

    Article  Google Scholar 

  5. Cuzick J, Thomas Cox J, Zhang G et al (2013) Human papillomavirus testing for triage of women with low-grade squamous intraepithelial lesions. Int J Cancer 132:959–966

    Article  CAS  PubMed  Google Scholar 

  6. Castle PE, Stoler MH, Wright TC Jr et al (2011) Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol 12:880–890

    Article  PubMed  Google Scholar 

  7. Castle PE, Cox JT, Schiffman M et al (2008) Factors influencing histologic confirmation of high-grade squamous intraepithelial lesion cytology. Obstet Gynecol 112:637–645

    Article  PubMed Central  PubMed  Google Scholar 

  8. Sherman ME, Castle PE, Solomon D (2006) Cervical cytology of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes. Cancer 108:298–305

    Article  PubMed  Google Scholar 

  9. Schiffman M, Castle PE, Jeronimo J et al (2007) Human papillomavirus and cervical cancer. Lancet 370:890–907

    Article  CAS  PubMed  Google Scholar 

  10. Muñoz N, Bosch FX, de Sanjosé S et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527

    Article  PubMed  Google Scholar 

  11. Clifford GM, Smith JS, Aguado T et al (2003) Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer 89:101–105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Onuki M, Matsumoto K, Satoh T et al (2009) Human papillomavirus infections among Japanese women: age-related prevalence and type-specific risk for cervical cancer. Cancer Sci 100:1312–1316

    Article  CAS  PubMed  Google Scholar 

  13. Matsumoto K, Oki A, Furuta R et al (2011) Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study. Int J Cancer 128:2898–2910

    Article  CAS  PubMed  Google Scholar 

  14. Nakamura Y, Matsumoto K, Satoh T et al (2014) Optimizing biopsy procedures during colposcopy for women with abnormal cervical cancer screening results: a multicenter prospective study. Int J Clin Oncol (in press)

  15. Gage JC, Hanson VW, Abbey K et al (2006) Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol 108:264–272

    Article  PubMed  Google Scholar 

  16. Satoh T, Matsumoto K, Fujii T et al (2013) Rapid genotyping of carcinogenic human papillomavirus by loop-mediated isothermal amplification using a new automated DNA test (Clinichip HPV™). J Virol Methods 188:83–93

    Article  CAS  PubMed  Google Scholar 

  17. Castle PE, Schiffman M, Wheeler CM et al (2009) Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 113:18–25

    Article  PubMed Central  PubMed  Google Scholar 

  18. Castle PE, Cox JT, Jeronimo J et al (2008) An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS). Obstet Gynecol 111:847–856

    Article  PubMed  Google Scholar 

  19. Brotherton JM, Fridman M, May CL et al (2011) Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 377:2085–2092

    Article  PubMed  Google Scholar 

  20. Markowitz LE, Hariri S, Lin C et al (2013) Reduction in human papillomavirus (HPV) prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010. J Infect Dis 208:385–393

    Article  CAS  PubMed  Google Scholar 

  21. Kavanagh K, Pollock KG, Potts A et al (2014) Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types. Br J Cancer 110:2804–2811

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Matsumoto K, Yaegashi N, Iwata T et al (2014) Monitoring the impact of a national HPV vaccination program in Japan (MINT Study): rationale, design and methods. Jpn J Clin Oncol 44:1000–1003

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Chizuko Fukui and Yoko Kuno, for technical assistance, Kokoro Hirai and Chieko Abe, for assistance with data collection, many other researchers who facilitated this study, and all the women who participated as study subjects. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan (grants #25462585 and #24791682) and the Ibaraki Clinical and Epidemiological Cancer Research Project. The supporting organizations were not involved in the design and implementation of the study, in collection, management, analysis, and interpretation of the data, or in preparation, review, or approval of the manuscript.

Conflict of Interest

KM has received lecture fees from Sekisui Medical Co., Ltd, Hologic Japan, Inc., Japan Vaccine Co., Ltd, GlaxoSmithKline K.K., and MSD K.K., and advisory fees from Hologic Japan, Inc. HY has received lecture and advisory fees from Japan Vaccine Co., Ltd, GlaxoSmithKline K.K., and MSD K.K.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan

    Yuko Nakamura, Koji Matsumoto, Toyomi Satoh, Akinori Oki, Hiroyuki Ochi & Hiroyuki Yoshikawa

  2. Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan

    Yuko Nakamura, Yukio Morishita & Masayuki Noguchi

  3. Department of Gynecology, Tsukuba Medical Center Hospital, Tsukuba, 305-8558, Japan

    Ken Nishide & Akiko Nozue

  4. Department of Obstetrics and Gynecology, Tsuchiura Kyodo General Hospital, Tsuchiura, 300-0053, Japan

    Koji Shimabukuro & Seiichi Endo

  5. Department of Gynecology, Ibaraki Prefectural Central Hospital, Kasama, 309-1793, Japan

    Kimihiro Nagai & Akinori Oki

Authors
  1. Yuko Nakamura
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  2. Koji Matsumoto
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  3. Toyomi Satoh
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  4. Ken Nishide
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  5. Akiko Nozue
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  6. Koji Shimabukuro
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  7. Seiichi Endo
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  8. Kimihiro Nagai
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  9. Akinori Oki
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  10. Hiroyuki Ochi
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  11. Yukio Morishita
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  12. Masayuki Noguchi
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  13. Hiroyuki Yoshikawa
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Corresponding author

Correspondence to Koji Matsumoto.

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Nakamura, Y., Matsumoto, K., Satoh, T. et al. HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study. Int J Clin Oncol 20, 974–981 (2015). https://doi.org/10.1007/s10147-015-0789-4

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  • DOI: https://doi.org/10.1007/s10147-015-0789-4

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