HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: A multicenter prospective cohort study

Koji Matsumoto, Hiroo Maeda, Akinori Oki, Naoyoshi Takatsuka, Toshiharu Yasugi, Reiko Furuta, Ranko Hirata, Akira Mitsuhashi, Takuma Fujii, Yasuo Hirai, Tsuyoshi Iwasaka, Nobuo Yaegashi, Yoh Watanabe, Yutaka Nagai, Tomoyuki Kitagawa, Hiroyuki Yoshikawa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. Methods: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. Results: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positivewomen than in DRB1*1302-negativewomen (median time, 8.9 months vs 14.2 months), although the differencewas not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. Conclusion: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume22
Issue number3
DOIs
Publication statusPublished - 01-03-2012
Externally publishedYes

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Cervical Intraepithelial Neoplasia
HLA Antigens
Cohort Studies
Alleles
Prospective Studies
Cell Biology
Papanicolaou Test
Colposcopy
Uterine Cervical Neoplasms
Biopsy
Antigens
Squamous Intraepithelial Lesions of the Cervix
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Matsumoto, Koji ; Maeda, Hiroo ; Oki, Akinori ; Takatsuka, Naoyoshi ; Yasugi, Toshiharu ; Furuta, Reiko ; Hirata, Ranko ; Mitsuhashi, Akira ; Fujii, Takuma ; Hirai, Yasuo ; Iwasaka, Tsuyoshi ; Yaegashi, Nobuo ; Watanabe, Yoh ; Nagai, Yutaka ; Kitagawa, Tomoyuki ; Yoshikawa, Hiroyuki. / HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3 : A multicenter prospective cohort study. In: International Journal of Gynecological Cancer. 2012 ; Vol. 22, No. 3. pp. 471-478.
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title = "HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: A multicenter prospective cohort study",
abstract = "Objective: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. Methods: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. Results: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positivewomen than in DRB1*1302-negativewomen (median time, 8.9 months vs 14.2 months), although the differencewas not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. Conclusion: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.",
author = "Koji Matsumoto and Hiroo Maeda and Akinori Oki and Naoyoshi Takatsuka and Toshiharu Yasugi and Reiko Furuta and Ranko Hirata and Akira Mitsuhashi and Takuma Fujii and Yasuo Hirai and Tsuyoshi Iwasaka and Nobuo Yaegashi and Yoh Watanabe and Yutaka Nagai and Tomoyuki Kitagawa and Hiroyuki Yoshikawa",
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Matsumoto, K, Maeda, H, Oki, A, Takatsuka, N, Yasugi, T, Furuta, R, Hirata, R, Mitsuhashi, A, Fujii, T, Hirai, Y, Iwasaka, T, Yaegashi, N, Watanabe, Y, Nagai, Y, Kitagawa, T & Yoshikawa, H 2012, 'HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: A multicenter prospective cohort study', International Journal of Gynecological Cancer, vol. 22, no. 3, pp. 471-478. https://doi.org/10.1097/IGC.0b013e3182439500

HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3 : A multicenter prospective cohort study. / Matsumoto, Koji; Maeda, Hiroo; Oki, Akinori; Takatsuka, Naoyoshi; Yasugi, Toshiharu; Furuta, Reiko; Hirata, Ranko; Mitsuhashi, Akira; Fujii, Takuma; Hirai, Yasuo; Iwasaka, Tsuyoshi; Yaegashi, Nobuo; Watanabe, Yoh; Nagai, Yutaka; Kitagawa, Tomoyuki; Yoshikawa, Hiroyuki.

In: International Journal of Gynecological Cancer, Vol. 22, No. 3, 01.03.2012, p. 471-478.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3

T2 - A multicenter prospective cohort study

AU - Matsumoto, Koji

AU - Maeda, Hiroo

AU - Oki, Akinori

AU - Takatsuka, Naoyoshi

AU - Yasugi, Toshiharu

AU - Furuta, Reiko

AU - Hirata, Ranko

AU - Mitsuhashi, Akira

AU - Fujii, Takuma

AU - Hirai, Yasuo

AU - Iwasaka, Tsuyoshi

AU - Yaegashi, Nobuo

AU - Watanabe, Yoh

AU - Nagai, Yutaka

AU - Kitagawa, Tomoyuki

AU - Yoshikawa, Hiroyuki

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Objective: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. Methods: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. Results: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positivewomen than in DRB1*1302-negativewomen (median time, 8.9 months vs 14.2 months), although the differencewas not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. Conclusion: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

AB - Objective: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. Methods: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. Results: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positivewomen than in DRB1*1302-negativewomen (median time, 8.9 months vs 14.2 months), although the differencewas not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. Conclusion: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

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