Intrauterine devices (IUDs) may offer protection against cervical cancer, suggests a Spanish study published in Lancet Oncology.

IUD use has been shown to reduce the risk of endometrial cancer, but little is known about the association with cervical cancer and HPV infection.

In the current study, Xavier Castellsagué and colleagues, from the L'Hospitalet de Llobregat (Barcelona, Spain), undertook a pooled analysis of 26 epidemiological studies involving almost 20,000 women to explore potential associations taking into account cervical HPV status and Pap screening history. One study by the International Agency for Research on Cancer included data from 10 case-control studies of cervical cancer undertaken in eight countries; and the other by the Institut Català included data from 16 HPV prevalence surveys of women from the general population in 14 countries. Information on IUD use was obtained by personal interview and HPV DNA was tested through PCR-based assays.

The results showed a strong inverse association between ever use of IUDs and cervical cancer (OR O.55, 95% CI 0.42-0.70; p<0.0001). A protective association for IUD was also noted for squamous-cell carcinoma (OR 0.56, 0.43-0.72; p<0.0001), adenocarcinoma and adenosquamous carcinoma (0.46, 0.22-0.97; p=0.035), but not among HPV positive women.

"We found a strong and consistent inverse association between IUD use and cervical cancer risk; women who reported previous IUD use had half the risk of developing cervical cancer compared with women with no history of IUD use," write the authors.

The associations found in the study, they add, strongly suggest that while IUD use does not modify the likelihood of prevalent HPV infection, it may affect the likelihood of HPV progression to cervical cancer. Speculating on the possible mechanisms, the authors suggest that IUDs may exert the protective effect through the induction of a reactive, chronic, low-grade, sterile inflammatory response in the endometrium that could modify the local mucosal immune status and the course of HPV infections.

Alternative theories, they put forward, include release of progesterone into the uterus affecting the natural history of HPV infection, or local trauma associated with insertion of the device inducing a small foci of chronic inflammation and a long lasting immune response.

In an accompanying commentary Karl Ulrich Petry, a colposcopist from Klinikum Wolfsburg (Wolfsburg, Germany) said: "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 went on to add that if large, prospective trials confirm a protective role of cervical trauma, we will need to appreciate that studies describing the natural course of cervical lesions have in fact been describing an n artificial course manipulated by biopsies, cervical brushes, loop insertion and other procedures.

Reference

X Castellsagué, M Diaz, S Vaccarella et al. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: a pooled analysis of 26 epidemiological studies. Lancet Oncology. DOI:10.1016/S1470-2045(11)70223-6

K Ulrich Petry. Loops in the natural history of cervical cancer. Lancet Oncology. Doi: 10.1016/S1470-2045(11)70255-8.