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Intrauterine Devices Lower Cervical Cancer Risk

  • Authors: News Author: Nick Mulcahy
    CME Author: Désirée Lie, MD, MSEd
  • CME/CE Released: 9/15/2011
  • Valid for credit through: 9/15/2012, 11:59 PM EST
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Target Audience and Goal Statement

This article is intended for primary care clinicians, gynecologists, and other specialists who care for women who use intrauterine devices.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Describe the effect of intrauterine device use on the risk for cervical cancer.
  2. Describe the effect of intrauterine device use on the risk for human papillomavirus infection.


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  • Nick Mulcahy

    Nick Mulcahy is a senior journalist for Medscape Hematology-Oncology. Before joining Medscape, Nick was a freelance medical news writer for 15 years, working for companies such as the International Medical News Group, MedPage Today, HealthDay, McMahon Publishing, and Advanstar. He is also the former managing editor of He can be contacted at [email protected].


    Disclosure: Nick Mulcahy has disclosed no relevant financial information.


  • Brande Nicole Martin

    CME Clinical Editor, Medscape, LLC


    Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.

CME Author(s)

  • Désirée Lie, MD, MSEd

    Clinical Professor; Director of Research and Faculty Development, Department of Family Medicine, University of California, Irvine at Orange


    Disclosure: Désirée Lie, MD, MSEd, has disclosed the following relevant financial relationship:
    Served as a nonproduct speaker for: "Topics in Health" for Merck Speaker Services

CME Reviewer(s)

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

Nurse Planner

  • Laurie E. Scudder, DNP, NP

    Nurse Planner, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC


    Disclosure: Laurie E. Scudder, DNP, NP, has disclosed no relevant financial relationships.

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Intrauterine Devices Lower Cervical Cancer Risk

Authors: News Author: Nick Mulcahy CME Author: Désirée Lie, MD, MSEdFaculty and Disclosures

CME/CE Released: 9/15/2011

Valid for credit through: 9/15/2012, 11:59 PM EST


Clinical Context

According to the current study by Castellsagué and colleagues, epidemiologic studies have consistently shown that the use of intrauterine devices (IUDs) reduces the risk for endometrial cancer, but the effect of IUD use on cervical cancer risk is not known. Because human papillomavirus (HPV) is now established as the cause of cervical cancer, HPV infection should be considered when the risk for cervical cancer with IUD use is examined.

This is a pooled analysis from 2 large studies consisting of 10 case-control studies done in 8 countries, and 16 studies of HPV prevalence from 16 countries. The goal of the analysis was to examine the risks for cervical cancer and HPV infection with IUD use.

Study Synopsis and Perspective

Women with a history of using IUDs have a reduced risk — by almost half — of developing cervical cancer, compared with women who never used the birth control devices, according to a new pooled analysis from European researchers.

Epidemiologic studies have consistently shown that IUD use reduces the risk for endometrial cancer, but the device's effect on the risk for cervical cancer has not been determined, say the researchers, led by Xavier Castellsagué, MD, from theInstitut Català d'Oncologia in Catalonia, Spain.

Previous studies have reported "inconsistent results" in cervical cancer, and none accounted for either HPV status or Pap screening history, they write in a paper published online September 13 in the Lancet Oncology.

IUD use has been suspected of causing cervical cancer since its clinical introduction in the 1930s, add the authors.

The epidemiologic study of nearly 20,000 women found that women who used IUDs had a 45% reduced risk for cervical cancer, compared with never users.

Specifically, the researchers found a "strong" inverse association between ever-use of IUDs and cervical cancer (odds ratio [OR], 0.55; < .0001) after adjustment for "relevant covariates." Those variables include the number of previous Pap tests that a woman has undergone.

A protective association was also noted for the 2 major cervical cancer histologic types — squamous cell carcinoma (OR, 0.56; P < .0001) and adenocarcinoma or adenosquamous carcinoma (OR 0.46; P = .035). However, there was no protective association among HPV-positive women (OR, 0.68; P =.11).

Thus, IUD use did not protect women against HPV infection, but did protect against the development of cervical cancer.

The researchers summarized what all these associations mean.

"The associations found in our study strongly suggest that IUD use does not modify the likelihood of prevalent HPV infection, but might affect the likelihood of HPV progression to cervical cancer," they write.

The results are "surprising" and should provide "restored confidence in the safety of IUDs," writes Karl Ulrich Petry, MD, from the Klinikum Wolfsburg in Germany, in an editorial that accompanies the study. The study "provides high-level evidence to contradict a widespread assumption that IUD use increases the risk of cervical cancer," he writes.

How IUDs Might Prevent Cervical Cancer

The mechanism of action by which IUDs protects against cervical cancer is not known, but the authors offer several explanations.

"One of the mechanisms by which IUDs might exert this protective effect is through the induction of a reactive, chronic, low-grade, sterile inflammatory response in the endometrium, endocervical canal, and cervix that could modify, via changes in the local mucosal immune status, the course of HPV infections," write the authors.

Another possible explanation accommodates an interesting finding in the study.

The investigators found that there was no difference in the protective effect by years of IUD use. Short-term users and those with use as long as 9 years were found to be protected, according to the odds ratio estimates.

"It can be postulated that the local trauma to the cervical tissue associated with insertion or removal of the device induces local small foci of chronic inflammation and a long-lasting immune response similar to that noted in patients after colposcopically guided punch biopsies," write the authors.

A theory that incorporates the concept of local trauma and subsequent immune response also appeals to Dr. Petry, the editorialist.

"I postulate that the tissue trauma associated with loop insertion induces a cellular immune response that might finally clear persistent HPV infections and preinvasive lesions," he writes.

The study's findings challenge some key elements of the "current model of the natural history of cervical cancer," adds Dr. Petry.

If prospective trials confirm the protective role of cervical trauma via the IUD loop insertion, then the medical world would "need to accept," he says, "that most studies of the natural course of cervical lesions in fact describe an artificial course, manipulated by biopsies cervical brushes, loop insertion, and other procedures."

The implications are profound, he suggests.

"It is very likely that we underestimated the true risk of progression of HPV infections and associated lesions, based on studies that relied on biopsy-proven diagnoses."

All of this means that "today's standard information for patients — that less than 1% of HPV infections progress to cancer" — does not reflect the true natural history that exists outside of clinical interventions, such as biopsies, Dr. Petry says. "The 6.5% lifetime risk for cervical cancer observed in remote areas without screening probably mirrors the true natural risk," he adds.

What About Screening Bias?

The study consisted of a pooled analysis of individual data from 2 large studies by the International Agency for Research on Cancer and Institut Català d'Oncologia research program on HPV and cervical cancer.

One study included data from 10 case–control studies of cervical cancer conducted in 8 countries; the other included data from 16 HPV prevalence surveys of women from the general population in 14 countries. There were 2205 women with cervical cancer and 2214 matched control women without cervical cancer from the case–control studies, and 15,272 healthy women from the HPV surveys.

"An important challenge" in interpreting the results can be found in the possible effect of a screening bias, say the authors. The insertion, follow-up, and removal of IUDs often involves "several visits to the gynecologist, providing many opportunities for these women to be directly diagnosed or screened for cervical cancer, through visual identification or repeated cervical cytology."

This is important because "the reduced risk of cervical cancer seen in IUD users might not be due to the biological effect of the device, but rather to the higher likelihood of more intensive cervical screening or diagnosis in these women compared with non-users," the authors point out.

But the investigators accounted for that possibility. "We estimated associations by specific strata of number of previous Pap smears women had until 12 months before diagnosis or study entry," they write. They did not find that more visits resulted in a significantly different likelihood of cervical cancer. "History of previous Pap smears did not significantly affect the observed inverse association between IUD use and risk of cervical cancer," they conclude.

Furthermore, the study population is an argument against the potential for screening bias, they say. "Since most of the populations included in these analyses are from developing areas of the world, where screening is opportunistic and has little effect in preventing cervical cancer, it is unlikely that screening bias would explain the observed inverse association."

Funding for this study came from the Instituto de Salud Carlos III; Agència de Gestió d'Ajuts Universitaris i Recerca; Marató TV3 Foundation; Bill & Melinda Gates Foundation; International Agency for Research on Cancer; European Community; Fondo de Investigaciones Sanitarias, Spain; Preventiefonds, the Netherlands; Programa Interministerial de Investigación y Desarrollo, Spain; Conselho Nacional de Desenvolvimiento Cientifico e Tecnologico, Brazil; and Department of Reproductive Health & Research, World Health Organization. The authors have disclosed no relevant financial relationships.

Lancet Oncol. Published online September 13, 2011. Abstract, Editorial

Related Link
The Association of Reproductive Health Professionals provides a downloadable patient education brochure, available in both English and Spanish, entitled A Woman's Guide to Understanding IUDs.

Study Highlights

  • The women in this study were recruited from 2 large series: one on HPV prevalence and the other, a case-control series on HPV and cervical cancer.
  • The population-based HPV prevalence surveys were conducted in 15 areas spanning 4 continents between 1993 and 2007.
  • Random age-stratified samples were surveyed in 5-year age groups, with participation ranging from 48% in Thailand to 96% in Colombia.
  • Women were interviewed face to face by trained interviewers using a standardized questionnaire.
  • Participants underwent a pelvic examination that included collection of cervical specimens for cytologic and HPV testing.
  • HPV testing was performed by use of polymerase chain reaction.
  • The case-control series was conducted between 1985 and 1997, in 11 countries with differing prevalence of cervical cancer.
  • Case patients were women with confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
  • Control participants were hospital-based or clinic-based patients matched by 5-year age groups to the case patients.
  • All women underwent a pelvic examination and 2 cervical scrapes for cytologic and HPV testing.
  • HPV testing was performed by use of polymerase chain reaction.
  • Logistic regression was used to assess the association between IUD use and HPV and cervical cancer.
  • In the HPV prevalence surveys, 13,179 women who tested negative for HPV and 2093 women who tested positive were included in the final pooled analysis.
  • Women who tested positive for HPV were younger, had a lower educational level, fewer pregnancies, fewer Papanicolaou tests, more sexual partners, more smoking, and earlier age of sexual debut.
  • Overall, 4.7% of women had an abnormal cytology result, ranging from 0.7% in Vietnam to 13.1% in Mongolia.
  • The case-control study had 2905 case patients and 2906 control participants from 11 studies.
  • 2205 case patients with cervical cancer and 2214 control women with information on IUD use were included in the final analysis.
  • Women with cervical cancer were more likely to be single, divorced, or widowed, to have a lower educational level, have more pregnancies, have a higher number of lifetime sexual partners, have fewer Papanicolaou tests, and have a younger age of sexual debut.
  • In both the prevalence and case-control studies, there was no association between IUD use and HPV infection among women.
  • The number of years of IUD use was also not associated with the risk for HPV infection.
  • The combined prevalence of IUD use from the prevalence and case-control studies was 13.0% among women with cervical cancer and 22.5% among control women.
  • There was an inverse association between IUD use and the risk for cervical cancer in all regions except Morocco.
  • After adjustment for covariates, there was a strong, significant inverse association between IUD use and cervical cancer (OR, 0.55; < .0001), which was seen for both histologic types of cervical cancer (squamous cell carcinoma and adenocarcinoma).
  • Compared with never-users of IUDs, the risk for cervical cancer was reduced by half in the first year of IUD use and was maintained with longer duration of IUD use.
  • The ORs by age groups ranged from 0.16 for ages 18 to 24 years and 0.51 for ages 25 to 42 years.
  • The OR was similar for HPV-negative and HPV-positive women.
  • The inverse association was also seen for both ever-users and never-users of oral contraceptives and among both users and nonusers of condoms.
  • The authors concluded that although HPV infection rates were not affected by the IUD, the risk for cervical cancer was reduced.
  • The authors postulated that the IUD may exert a chronic inflammatory response in the cervix that protects against the progression of HPV infection to cervical cancer.

Clinical Implications

  • IUD use is associated with a reduced risk for cervical cancer.
  • IUD use is not associated with a reduced or increased risk for HPV infection among women.

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