Iga And Cervical Cancer

Cervical carcinoma has been one of the most common causes of cancer related death in women for many years. Although the mortality rates have fallen by 50% in the last three decades in developed countries, it continues to be a major gynecologic cancer in the underdeveloped countries. There were 15,700 new cases of invasive cervical cancer and 4900 deaths in 1996 [46], Lower socioeconomic status, early age of sexual activity, multiple sexual partners and smoking are considered to be predisposing risk factors. Human papilloma virus has attracted interest as an etiological agent in precancerous lesions and invasive cancer of the cervix. More than 66 types of HPV have been isolated and many of them are associated with genital warts. Protein products of HPV-16 (E7 protein) and HPV-18 (E6 protein) have oncogenic potential and have been associated with cervical cancer [84, 85],

Mann et al. [86] examined the sera of 186 cases of invasive cervical cancer and 172 matched controls. They found a strong association of IgA and IgG antibodies to E7 peptide of HPV with invasive cervical cancer. Lehtinen et al. [87] found high serum IgA antibody levels to HPV 16 (E2 protein) in 122 women with cervical carcinoma, compared to age-matched controls. Casamassima et al. [88] determined total IgA level in cervical smears of women with cervical dysplasia and other benign lesions and controls. They found the highest IgA levels in patients with dysplasia.

The Epstein-Barr virus has also been implicated in the etiology of cervical carcinomas. Se Thoe et al. [89] found high IgA antibody levels in 83% of patients with cervical carcinoma and 75% patients with cervical intraepithelial neoplasia (CIN) and none of the controls.

Sasagawa et al. [90, 91] studied IgA and IgG antibodies against HPV-16 like particles in 104 women with various cervical diseases and age-matched controls. IgA and IgG responses were higher in women with cervical cancer.

Dillner et al. [92] conducted a seroepidemiological study in two counties of northern Sweden that were low risk for cervical cancer. They found a strong association of the antibodies with cervical cancer. Dillner et al. [93] also evaluated 94 cases of cervical cancer and 188 controls for IgA and IgG antibodies against HP-16 viral antigens and found a strong association between the antibody response and cervical cancer.

Reeves et al. [94] also found antibodies to HPV 16 proteins (peptide 245 and E7) in patients with CIN and invasive cervical cancer more frequently than in women with lesions not associated with papilloma virus.

Juranic et al. [95] evaluated patients with cervical carcinoma before and after radiotherapy. IgA and IgG levels were elevated in patients with cervical cancer before therapy and declined to near normal levels postirradiation. IgM levels were in the range of the normal controls and remained so in the post treatment period. The levels of circulating immune complexes (CIC) did not change significantly after treatment. They concluded that IgA and IgG levels and CIC's may be of diagnostic value in cervical carcinoma and may be useful for monitoring response to therapy.

These studies suggest that HPV and possibly EBV have a causative role in cervical carcinoma and that IgA levels and IgA antibody levels may be useful in the diagnosis and monitoring of this disease. IgA levels are increased in dysplasia and early neoplastic lesions of cervical cancer. The IgA responses appear to be antigen driven, specifically targeted to HPV, EBV and herpes viruses (Table 3).

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