Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study

International Journal of Clinical Oncology volume 17, pages233–239(2012)Cite this article

Abstract

Objective

To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy.

Methods

In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy.

Results

In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73).

Conclusion

In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.

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Acknowledgments

The authors thank Dr. Tadahito Kanda (Center for Pathogen Genomics, National Institute of Infectious Diseases, Tokyo, Japan) for his comments on the study design and the manuscript; Mr. Masafumi Tsuzuku (Department of Cytopathology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Japan) for his cytologic review; many other researchers who facilitated this study; and all the women who participated in the study. This work was supported by a grant from the Ministry of Education, Science, Sports and Culture of Japan (grant # 12218102).

Conflict of interest

We declare that we have no conflict of interest relevant to this article. The supporting organization played no role in the design and implementation of the study; the collection, management, analysis, and interpretation of the data; and the preparation, review, or approval of the manuscript.

Author information

Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, 305-8575, Japan

    Koji Matsumoto, Akinori Oki & Hiroyuki Yoshikawa

  2. Departments of Gynecology and Cytopathology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo, 135-8550, Japan

    Yasuo Hirai

  3. Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo, 135-8550, Japan

    Reiko Furuta & Tomoyuki Kitagawa

  4. Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan

    Naoyoshi Takatsuka

  5. Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, 113-8655, Japan

    Toshiharu Yasugi & Kei Kawana

  6. Department of Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical University, Saitama, 350-8550, Japan

    Hiroo Maeda

  7. Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan

    Akira Mitsuhashi

  8. Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, 160-8582, Japan

    Takuma Fujii

  9. Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga, 849-8501, Japan

    Tsuyoshi Iwasaka

  10. Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, 980-8574, Japan

    Nobuo Yaegashi

  11. Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka, 589-8511, Japan

    Yoh Watanabe

  12. Department of Obstetrics and Gynecology, Faculty of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan

    Yutaka Nagai

Authors
  1. Koji Matsumoto
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  2. Yasuo Hirai
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  3. Reiko Furuta
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  4. Naoyoshi Takatsuka
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  9. Takuma Fujii
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  10. Kei Kawana
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  11. Tsuyoshi Iwasaka
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  12. Nobuo Yaegashi
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  13. Yoh Watanabe
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  14. Yutaka Nagai
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  15. Tomoyuki Kitagawa
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  16. Hiroyuki Yoshikawa
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For Japan HPV and Cervical Cancer (JHACC) Study Group

Corresponding author

Correspondence to Koji Matsumoto.

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Cite this article

Matsumoto, K., Hirai, Y., Furuta, R. et al. Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study. Int J Clin Oncol 17, 233–239 (2012). https://doi.org/10.1007/s10147-011-0280-9

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Keywords

  • Low-grade squamous intraepithelial lesion
  • Colposcopy
  • Human papillomavirus
  • Cervical intraepithelial neoplasia