A population-based seroepidemiological study of cervical cancer.

The epidemiology of cervical cancer indicates the presence of a sexually transmitted risk factor, attributable at least in part to infection with human papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of HPV and cervical cancer in the counties of Västerbotten and Norrbotten in Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of incident cervical cancer were matched against 188 age- and sex-matched controls derived from a population-based blood bank. IgG and IgA antibodies were measured against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis, cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and 2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR = 3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or bovine papillomavirus were, on their own, not significantly associated with cervical cancer, but seropositivity against multiple infections was associated with a successively increased relative risk. An increased risk was also found for IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The results indicate that several HPV antibodies are strongly associated with cervical cancer, providing further seroepidemiological support for an etiological role of HPV in cervical cancer.

[1]  M. Lehtinen,et al.  Evaluation of serum antibody response to a newly identified B-cell epitope in the minor nucleocapsid protein L2 of human papillomavirus type 16. , 1993, Clinical and diagnostic virology.

[2]  J. Dillner.  Disappearance of antibodies to HPV 16 E7 after treatment for cervical cancer , 1993, The Lancet.

[3]  J. Dillner,et al.  Antibodies against papillomavirus antigens in cervical secretions from condyloma patients , 1993, Journal of clinical microbiology.

[4]  J. Dillner,et al.  Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma , 1993, International journal of cancer.

[5]  K. Holmes,et al.  A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection , 1992, The New England journal of medicine.

[6]  K. Macrae,et al.  A colposcopic case-control study of cervical squamous intraepithelial lesions in women with anogenital warts. , 1992, Genitourinary medicine.

[7]  J. Dillner,et al.  Levels of immunoglobulin G antibodies against defined epitopes of the L1 and L2 capsid proteins of human papillomavirus type 6 are elevated in men with a history of condylomata acuminata , 1992, Journal of clinical microbiology.

[8]  M. Lehtinen,et al.  Pre‐ and posttreatment serum antibody responses to HPV 16 E2 and HSV 2 ICP8 proteins in women with cervical carcinoma , 1992, Journal of medical virology.

[9]  M. Lehtinen,et al.  Predominance of serum antibodies to synthetic peptide stemming from HPV 18 open reading frame E2 in cervical adenocarcinoma. , 1992, Journal of clinical pathology.

[10]  D. Galloway,et al.  Human antibodies recognize multiple distinct type-specific and cross-reactive regions of the minor capsid proteins of human papillomavirus types 6 and 11 , 1992, Journal of virology.

[11]  F. X. Bosch,et al.  Antibodies to HPV-16 E6 and E7 proteins as markers for HPV-16-associated invasive cervical cancer. , 1992, Virology.

[12]  M. Schiffman,et al.  Recent progress in defining the epidemiology of human papillomavirus infection and cervical neoplasia. , 1992, Journal of the National Cancer Institute.

[13]  M. Krcmar,et al.  Epitope mapping of the human papillomavirus type 16 E4 protein by means of synthetic peptides. , 1992, The Journal of general virology.

[14]  J. Dillner,et al.  Antigenic and immunogenic epitopes shared by human papillomavirus type 16 and bovine, canine, and avian papillomaviruses , 1991, Journal of virology.

[15]  W. Reeves,et al.  Evaluation of a test based on baculovirus-expressed glycoprotein G for detection of herpes simplex virus type-specific antibodies. , 1991, The Journal of infectious diseases.

[16]  H. Hausen.  Viruses in human cancers , 1991 .

[17]  Moyses Szklo,et al.  Herpes simplex virus type 2: A possible interaction with human papillomavirus types 16/18 in the development of invasive cervical cancer , 1991, International journal of cancer.

[18]  P. Sova,et al.  Mapping of serologically relevant regions of human cytomegalovirus phosphoprotein pp150 using synthetic peptides. , 1991, The Journal of general virology.

[19]  M. Campion,et al.  Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm , 1991, Journal of virology.

[20]  M. Brenes,et al.  Occurrence of IgA and IgG antibodies to select peptides representing human papillomavirus type 16 among cervical cancer cases and controls. , 1990, Cancer research.

[21]  M. Krcmar,et al.  Synthetic peptides derived from E7 region of human papillomavirus type 16 used as antigens in ELISA. , 1990, The Journal of general virology.

[22]  R. Brasseur,et al.  Identification of seroreactive regions of the human papillomavirus type 16 protein E4, E6, E7 and L1. , 1990, The Journal of general virology.

[23]  I. Hirsch,et al.  Presence of antibody reactive with synthetic peptide derived from L2 open reading frame of human papillomavirus types 6b and 11 in human sera. , 1990, Acta virologica.

[24]  D. Galloway,et al.  Evidence of prevalent genital-type human papillomavirus infections in adults and children. , 1990, The Journal of infectious diseases.

[25]  J. Dillner,et al.  Evaluation of enzyme-linked immunosorbent assays with two synthetic peptides of Epstein-Barr virus for diagnosis of infectious mononucleosis. , 1990, The Journal of infectious diseases.

[26]  J. Dillner,et al.  Mapping of linear epitopes of human papillomavirus type 16: The L1 and L2 open reading frames , 1990, International journal of cancer.

[27]  W. Rawls,et al.  Antibodies to human papillomavirus type 16 in patients with cervical neoplasia , 1990, The Lancet.

[28]  J. Dillner,et al.  Serological responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri , 1990, Journal of clinical microbiology.

[29]  R. Kimmig,et al.  Antibodies against the human papillomavirus type 16 early proteins in human sera: correlation of anti-E7 reactivity with cervical cancer. , 1989, Journal of the National Cancer Institute.

[30]  H. Adami,et al.  Natural history of cervical neoplasia: consistent results obtained by an identification technique. , 1989, British Journal of Cancer.

[31]  E. de Villiers,et al.  Multiple infections in cases of cervical cancer from a high‐incidence area in tropical Africa , 1989, International journal of cancer.

[32]  J. Dillner,et al.  A synthetic peptide defines a serologic IgA response to a human papillomavirus-encoded nuclear antigen expressed in virus-carrying cervical neoplasia. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Monini,et al.  Search for human papillomavirus, herpes simplex virus and c‐myc oncogene in human genital tumors , 1989, International journal of cancer.

[34]  D. Galloway,et al.  Human antibodies react with an epitope of the human papillomavirus type 6b L1 open reading frame which is distinct from the type-common epitope , 1989, Journal of virology.

[35]  W. Haenszel,et al.  Cigarette smoking and invasive cervical cancer. , 1986, JAMA.

[36]  J. Dillner,et al.  Antibodies against a synthetic peptide identify the Epstein-Barr virus-determined nuclear antigen. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[37]  P. Baird.  SEROLOGICAL EVIDENCE FOR THE ASSOCIATION OF PAPILLOMAVIRUS AND CERVICAL NEOPLASIA , 1983, The Lancet.

[38]  I. Julander,et al.  Enzyme-linked immunosorbent assay for antibodies against teichoic acid in patients with staphylococcal infections , 1983, Journal of clinical microbiology.

[39]  H. Hausen.  HUMAN GENITAL CANCER: SYNERGISM BETWEEN TWO VIRUS INFECTIONS OR SYNERGISM BETWEEN A VIRUS INFECTION AND INITIATING EVENTS? , 1982, The Lancet.

[40]  J. Melnick,et al.  Measurement of antibodies to herpesvirus types 1 and 2 in human sera. , 1970, Journal of immunology.

[41]  W. Drew,et al.  Cytomegalovirus as a Sexually Transmitted Disease , 1993 .

[42]  H. Pfister.  Human papillomaviruses and genital cancer. , 1987, Advances in cancer research.

[43]  M. Lehtinen,et al.  Immunoblotting and enzyme-linked immunosorbent assay analysis of serological responses in patients infected with herpes simplex virus types 1 and 2. , 1985, Intervirology.