Induction of an inflammatory response in the cervix following infection with human papillomavirus (HPV) might lead to an increased risk of cervical cancer — this is the conclusion of a new study by Mary Carrington and colleagues.

Natural killer (NK) cells are an important component of the innate immune response to viruses and tumours, and their activation depends on the balance of signals from inhibitory and activating receptors, such as the killer-cell immunoglobulin-like receptors (KIRs). KIRs engage specific HLA class I proteins at the surface of target cells, and the numerous possible KIR and HLA haplotypes mean that there is huge scope for variation in HLA–KIR interactions. Carrington et al. show that certain combinations of HLA class I and KIR alleles are associated with a higher risk of developing cervical cancer.

The authors examined the frequencies of HLA class I alleles among women with and without cervical cancer. They found that some HLA allelic groups that are known to encode high-affinity ligands for inhibitory KIRs — HLA-Cw group 2 and HLA-Bw4 alleles — are associated with reduced risk of the disease. They also found that some activating KIRs — such as KIR3DS1 — are expressed at a higher frequency in individuals who have cervical cancer than in those who do not. Furthermore, when the authors examined the effects of carrying KIR3DS1 together with HLA-Cw group 2 and HLA-Bw4 alleles, they found a gradient of susceptibility to cervical cancer.

Carrington and colleagues point out that lesions in women with oncogenic HPV infections are often associated with concomitant inflammation of the cervix, and they suggest that NK-cell activation might promote the development of cancer by contributing to local inflammation. However, although inflammation has been associated with several other cancers, further studies are needed to clarify the relationship between inflammation, transformation and the role of NK cells.