Comparison of Human Papillomavirus Infection and Cervical Cytology in Women Using Copper-Containing and Levonorgestrel-Containing Intrauterine Devices

Lekovich, Jovana P.; Amrane, Selma; Pangasa, M.; Pereira, Nigel; Frey, M.K.; Varrey, Aneesha; Holcomb, Kevin

doi:10.1097/aog.0000000000000760

Cited by 22 publications

(28 citation statements)

References 25 publications

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“…Conversely, administration of agonist anti-CD40 mAb to LNG-treated mice at dpi 1 produced Chlamydia burden and pulmonary inflammation at 12 dpi that closely resembled that seen in placebo-pelleted controls. Thus, while our use of sustained-release LNG pellets in a mouse model of respiratory C. trachomatis infection may not fully recapitulate the immunomodulatory effects of LNG-IUS use in the genital tract of women, the elevated chlamydial burden we detected in LNG-treated mice at 12 dpi is entirely consistent with the delayed eradication of genital HPV observed in women using LNG-IUS12.…”

Section: Discussionmentioning

confidence: 71%

“…Among the 66 women in that study diagnosed with high-risk HPV genital infection prior to IUS insertion, 70% initiating copper-containing IUS use vs. 42% initiating LNG-IUS use cleared infection during the first year after insertion12. Such results implied LNG, and not the mere presence of an IUS, was the variable more closely associated with delayed HPV clearance.…”

Section: Discussionmentioning

confidence: 88%

“…Also underexplored are the in vivo effects of LNG on pathogen clearance. One retrospective study did observe reduced genital clearance of high-risk human papillomavirus (HPV) in women using LNG-IUS12, while Chlamydia trachomatis clearance was delayed in baboons infected subsequent to human-use LNG-IUS insertion13. Notably however, the immunomodulatory properties of LNG responsible for these experimental and clinical observations have not been defined.…”

mentioning

confidence: 99%

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Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

Calla

Miguel

Mei

et al. 2016

Sci Rep

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The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems for long-acting reversible contraception provides strong impetus to define immunomodulatory properties of this exogenous progestin. In initial in vitro studies herein, we found LNG significantly impaired activation of human dendritic cell (DCs) and their capacity to promote allogeneic T cell proliferation. In follow-up studies in a murine model of intranasal Chlamydia trachomatis infection, we analogously found that LNG treatment prior to infection dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at 2 days post infection (dpi). At 12 dpi, we also detected significantly fewer CD4+ and CD8+ T cells in the lungs of LNG-treated mice. This inhibition of DC activation and T cell expansion in LNG-treated mice also delayed chlamydial clearance and the resolution of pulmonary inflammation. Conversely, administering agonist anti-CD40 monoclonal antibody to LNG-treated mice at 1 dpi restored lung T cell numbers and chlamydial burden at 12 dpi to levels seen in infected controls. Together, these studies reveal that LNG suppresses DC activation and function, and inhibits formation of pathogen-specific T cell immunity. They also highlight the need for studies that define in vivo effects of LNG use on human host response to microbial pathogens.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

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Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

Calla

Miguel

Mei

et al. 2016

Sci Rep

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“…The studies included in the meta-analyses were mostly older studies, which suggests these women were more likely copper-IUD users. One study has suggested that the effect on hrHPV biology may be different, in which copper-IUD users were more likely to clear hrHPV infections than levonorgestrel-releasing IUD users [15]. A caseecontrol study with recent IUD use also found a trend toward a protective effect of copper-IUDs, but an increased risk of CIN2þ for levonorgestrel-releasing IUDs [12].…”

Section: Parametersmentioning

confidence: 99%

Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: a population-based study

Loopik

IntHout

Melchers

et al. 2020

European Journal of Cancer

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Objective: Hormonal contraceptive use has been associated with the development of cervical cancer, although inconsistent results are reported on the association with intrauterine device (IUD) use. The aim of this study was to evaluate the association between the type of contraceptive use and the development of cervical intraepithelial neoplasia grade III or worse Abbreviations: ASC-H, atypical squamous cells e cannot rule out high-grade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; hrHPV, high-risk human papillomavirus; HSIL, high-grade squamous intraepithelial lesion; IUD, intrauterine device; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion or malignancy; NOS, not otherwise specified; OC, oral contraceptive; PALGA, the nationwide network and registry of histo-and cytopathology in the Netherlands.

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“…Other studies have suggested that the effect of these IUDs on HPV biology may be different. 15 Our study was conducted among young women in the US, and most of the IUD use was in the late 2000s, therefore many of our IUD users were likely using LNG-releasing IUDs. Older studies, including the meta-analysis showing that IUDs are associated with decreased risk of cervical cancer, 4 likely included mostly copper IUDs.…”

Section: Commentmentioning

confidence: 99%

The effect of intrauterine devices on acquisition and clearance of human papillomavirus

Averbach

Smith‐McCune

et al. 2017

American Journal of Obstetrics and Gynecology

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Background Previous studies have shown a decrease in cervical cancer associated with intrauterine device use. It has been hypothesized that intrauterine device use may alter the natural history of human papillomavirus infections, preempting development of precancerous lesions of the cervix and cervical cancer, but the effect of intrauterine devices on the natural history of human papillomavirus infection and subsequent development of cervical cancer is poorly understood. Objective The purpose of this study was to evaluate the association between intrauterine device use and cervical high-risk human papillomavirus acquisition and clearance. Study Design This is a prospective cohort study conducted between October 2000 and June 2014 among 676 sexually active young women enrolled from family planning clinics in San Francisco, California. Data was analyzed using a Cox proportional hazards model, including time varying indicators of intrauterine device use, and adjusting for fixed and time-dependent predictor variables. Results A total of 85 women used an intrauterine device at some time during follow up. Among 14,513 study visits, women reported intrauterine device use at 505 visits. After adjusting for potential behavioral confounders, there was no association between intrauterine device use and or human papillomavirus acquisition, HR= 0.50 (95% CI 0.20–1.23) p=0.13 or clearance of human papillomavirus infection, HR=1.44 (95% CI 0.76–2.72) p=0.26. Conclusions Current intrauterine device use is not associated with acquisition or persistence of human papillomavirus infection. Intrauterine device use is safe among women with human papillomavirus infections and at risk for human papillomavirus acquisition. Intrauterine device use may play a role further downstream in the natural history of cervical cancer by inhibiting the development of precancerous lesions of the cervix in intrauterine device -infected women, or enhancing clearance of established precancerous lesions.

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Comparison of Human Papillomavirus Infection and Cervical Cytology in Women Using Copper-Containing and Levonorgestrel-Containing Intrauterine Devices

Abstract: II.

Cited by 22 publications

References 25 publications

Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection

Oral contraceptive and intrauterine device use and the risk of cervical intraepithelial neoplasia grade III or worse: a population-based study

The effect of intrauterine devices on acquisition and clearance of human papillomavirus

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