Document Type

Article

Publication Date

9-2026

Identifier

DOI: 10.1038/s41416-026-03508-9; PMCID: PMC13534713

Abstract

BACKGROUND: Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluated the associations of these two contraceptive exposures with ovarian tumor immune infiltration.

METHODS: This study assessed associations of IUD and OC use with tumor immune features via multiplex immunofluorescence in 24 ovarian tumor tissue microarrays from four case-control and two cohort studies. Multivariable-adjusted beta-binomial models estimated the odds of tumor T cell positivity by contraceptive history.

RESULTS: High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3+ mean=3.4%, SD = 6.1) and each T cell subtype. Ever (vs. never) IUD use was modestly associated with increased cytotoxic T cell infiltration (CD3+CD8+ OR:1.14, 95% CI:0.99-1.32), which was stronger among those with a history of endometriosis, postmenopausal women, and smokers. Conversely, OC use ≥1 year (vs. never) was associated with lower cytotoxic T cell odds (CD3+CD8+ OR:0.89, 95% CI:0.79-1.00; p-het=0.008). Increased odds of terminal T cell exhaustion were observed for IUD use only (CD3+PD1+TIM3+ OR:1.53, 95% CI:0.99-2.36), which was stronger among those who had ever used genital powder or BMI > 25 kg/m2.

CONCLUSIONS: Pre-diagnostic contraception use may influence ovarian tumor immunity and may modulate cancer susceptibility.

Journal Title

British journal of cancer

Volume

135

Issue

6

First Page

972

Last Page

982

MeSH Keywords

Female; Humans; Intrauterine Devices; Ovarian Neoplasms; Middle Aged; Contraceptives, Oral; Case-Control Studies; Adult; Lymphocytes, Tumor-Infiltrating; T-Lymphocytes, Cytotoxic; Cohort Studies; Aged

PubMed ID

42365137

Keywords

Intrauterine Devices; Ovarian Neoplasms; Oral Contraceptives; Case-Control Studies; Tumor-Infiltrating Lymphocytes; Cytotoxic T-Lymphocytes; Cohort Studies

Comments

Grants and funding

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Publisher's Link: https://www.nature.com/articles/s41416-026-03508-9

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