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

Abstract

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.

Mucosal Immunity in the Human Female Reproductive Tract

“…Local intravaginal immunization with proteins or biologically inert antigens required repeated and large doses (Roche and Crum, 1991;Russell, 2002). Furthermore, intravaginal immunization with C. albicans elicited a modest and strictly local antibody response (Waldman et al, 1972).…”

“…The IgA of cervical mucus is primarily S-IgA, with a small component of monomeric IgA (mIgA) (Vaerman and Férin, 1974;Roche and Crum, 1991;Kutteh and Mestecky, 1994;Kutteh et al, 1993). With respect to the distribution of IgA subclasses, the female genital tract secretions resemble the lower intestinal tract: IgA1 and IgA2 are present in approximately equal proportions (Kutteh et al, 1996).…”

Contributions in the domain of cancer research: Review¶Human papillomaviruses and their role in cervical cancer

“…Cigarette smoke by-products are present in the cervical mucus of active and passive smokers and these chemicals could increase cancer risk via their mutagenic effects on cervical cells [33]. Smoking is also thought to decrease the number of antigen-presenting Langerhans cells in the cervix, which might lessen the local immunity to HPV infection [34,35]. The possibility that progesterone and/or oestrogen from oral contraceptives might play a role in HPV-induced cervical cancer has been investigated intensively.…”