Local immunity and the uterine cervix: implications for cancer-associated viruses

Studies of cervical secretions as well as cells composing the endocervix have provided evidence for a functional and potentially important immunological system in the mucosa of that organ. The availability of the tools of cell biology as well as three agents that may be used as probes to infect cervical mucosa experimentally has made possible a detailed approach to define the structural and functional characteristics of local cervical immunity. A long-term goal of these studies is to determine how the cervical immune response may be regulated to reduce local viral replication and virus-associated diseases. With Langerhans cells for antigen presentation, cervical immune responses generally remain detectable for more than 30 days, are predominantly of the IgA isotype, can be influenced by estrogen or progesterone, and are best elicited by local rather than systemic exposure to antigen. Cervical immune responses to the human papillomaviruses (HPV) are of particular importance in this regard because this virus is associated with cervical neoplasia. While responses in serum to HPV-16 proteins L1, E4, and E7 has been found in up to 78% of persons with HPV-associated cervical neoplasms, data showing that a local response of comparable frequency consistently occurs have yet to be confirmed. The current status of local HPV-16-specific immunoglobulin as a potentially useful indicator of HPV-16-related infection or pre-cancer is controversial, and is confounded by several potentially important factors, including patient age, estrogen/progesterone level, smoking status, and sample admixture with serum immunoglobulin.