HPV virus description
Human papillomavirus (HPV) is non-enveloped double stranded DNA virus and it is found in 99.7% of patients with cervical cancer (1). Nowadays, more than 170 types of HPVs are identified and HPV types are subdivided into cervical cancer causing high-risk types (16, 18, 31, 45, 52, 58) and wart causing low-risk types (6, 11) (2, 3). When the infections with high-risk HPVs persist for a long time, invasive cervical cancer may be developed from cervical intraepithelial neoplasia (CIN) I, II and III which termed as pre-cancerous stages (4-6).
HPV contains two late proteins (L1, L2) and six early proteins (E1, E2, E4, E5, E6, E7) (7). As the major capsid protein, L1 represents about 90% of total HPV protein and is mainly involved in virus-host cell interaction (8). E6 and E7, oncoproteins of HPV, are involved in cell cycle controlling and DNA repairing via interacting with p53 and pRb cellular proteins, and play major role in induction and maintenance of malignant cellular transformation. When HPV infects basal layer of the cervix, its DNA can integrate into the host gene during the carcinogenesis, and results in continuous expression of viral proteins (9). Therefore, these viral proteins can stimulate the immune system to produce serum antibodies against them. Antibodies against HPV L1 are considered to be critical markers of cumulative exposure to the virus and it was found to be an independent prognostic factor for overall survival in patients with cervical cancer (10, 11). Antibodies against to E6 or E7 proteins of HPV16/HPV18 are regarded as potential markers for discriminating cervical cancer group from normal cytology. Therefore, levels of serum antibodies against HPV viral proteins have been provided as important clues for understanding the natural history of infection and also have been considered to be critical factors to estimate the risk of pathogenesis of cervical cancer.
Sero-epidemiological studies have been progressing over the past 10 years, but there are some limitations in these serological assays as follows. The levels of HPV specific antibody were conducted mostly in normal and cancer groups in the previous studies, thus those in CIN stages during the cancer development have not been evaluated concretely. Another limitation is difficult to prepare HPV viral proteins to detect varied types of serum antibodies because the diverse types of HPV and viral proteins. Therefore, only two or three types of antigen-specific HPV antibodies have been evaluated in the previous studies.
