Biomedical subjects

J Dillner

Publications and source records attributed to J Dillner.

At least 73 records · Page 4Linked to original sources

PubMed1998

Trends in seroprevalence of human papillomavirus type 16 among pregnant women in Stockholm, Sweden, during 1969-1989.

To assess long-term trends in the prevalence of oncogenic human papillomavirus (HPV) infection, we performed a cross-sectional serosurvey of the seroprevalence of the major oncogenic HPV type, HPV16, among 3,512 pregnant women undergoing population-based serological screening at the first trimester of pregnancy in the same catchment area in Stockholm, Sweden, during 1969, 1983 or 1989. The overall HPV16 seroprevalence rates were 16% in 1969, 22% in 1983 and 21% in 1989. Seroprevalence was significantly increased, comparing both 1969 vs. 1983 (p = 0.0005) and 1969 vs. 1989 (p = 0.008). By comparison, the previously reported herpes simplex 2 (HSV-2) seroprevalence in the same women increased from 17% in 1969 to 32% in 1983 and 33% in 1989, whereas the seroprevalence rates of HSV-1 were the same (69% in 1969, 63% in 1983 and 68% in 1989). Odds ratios for HPV 16-positive women to also be HSV-2-positive were 1.8 in 1969 (p < 0.005), 1.1 in 1983 (p = NS) and 1.0 in 1989. Our results suggest that both HSV-2 and HPV16 became more generally spread in the Swedish population between 1969 and 1983 but that the spread has been stable during the 1980s.

Adult↗

PubMed1998

Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer.

Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyzed for the presence of IgG antibodies against 4 HPV types and against Chlamydia. The presence of antibodies against HPV type 18 was associated with a 2.6-fold increased risk of developing prostate cancer during follow-up (p < 0.005). HPV type 16 tended to be associated with subsequent prostate-cancer occurrence (relative risk: 2.4, p = 0.06), whereas seropositivity for HPV type 11 or type 33 or for Chlamydia was not associated with risk. The results suggest that infection with oncogenic HPV might be involved in the etiology of a minority of prostate cancers.

Adult↗

PubMed1998

A population-based study of human papillomavirus deoxyribonucleic acid testing for predicting cervical intraepithelial neoplasia.

OBJECTIVE: Our purpose was to determine the predictive values of primary or secondary screening for cervical human papillomavirus infection for cytologic detection of cervical intraepithelial neoplasia. STUDY DESIGN: Most of the 254 women referred for colposcopy in Västerbotten County in Sweden during October 1993 through December 1995 and 320 age-matched women from the general population were screened for human papillomavirus deoxyribonucleic acid by nested general-primer polymerase chain reaction. RESULTS: Ninety-six percent of women with high-grade cervical intraepithelial neoplasia had human papillomavirus, compared with 4% of women with normal findings (odds ratio 606; 95% confidence interval 137 to 5607). Thirty-seven percent of referred women and 48% of referred women >39 years old had mostly minor cytologic abnormalities with no human papillomavirus. The human papillomavirus-associated positive predictive value for cervical intraepithelial neoplasia was 76% in the colposcopy group and 11% in the general population, whereas the negative predictive value was >97% in both populations. CONCLUSION: Testing for human papillomavirus deoxyribonucleic acid seems diagnostically useful among women referred for colposcopy.

Adult↗

PubMed1998

Stability over time of serum antibody levels to human papillomavirus type 16.

The stability over time of serum IgG antibody levels to human papillomavirus type 16 (HPV-16) was determined by comparing the HPV-16 capsid antibody levels in serial serum samples of an age-stratified random subsample of 1656 primiparous mothers resident in Helsinki who were followed until their second pregnancy, on average 29.5 months later. The correlation between the first and second pregnancy HPV-16 serum antibody levels of the same woman was high, even when >4 years had elapsed between pregnancies (r = .822). Between negativity, indeterminate results, or quartiles of positivity, the predictive values for being classified in the same category on both occasions ranged between 42% and 91%. Correlation coefficients, predictive values, and kappa coefficients between serial samples all were comparable with those of repeat analyses of the same sample, indicating that HPV capsid antibody levels are generally stable during several years of follow-up.

Adolescent↗

PubMed1998

Herpes simplex virus and human papillomavirus in a population-based case-control study of cervical intraepithelial neoplasia grade II-III.

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.

Antibodies, Viral↗

PubMed1998

Immunoglobulin A, G, and M responses to L1 and L2 capsids of human papillomavirus types 6, 11, 16, 18, and 33 L1 after newly acquired infection.

OBJECTIVES: We performed a study to establish the pattern of serological reactivity for immunoglobulins (Ig), to capsids of human papilloma virus (HPV) after new HPV infection in two groups of subjects. METHODS: The pattern of serological reactivity after acquisition of infection with HPV was investigated by measuring IgA, IgM, and IgG antibodies to capsids containing L1 and L2 proteins of HPV types 6, 11, 16, 18, and 33 in longitudinal studies of groups with different patterns of sexual activity. Individuals who tested negative for HPV DNA by the polymerase chain reaction at enrolment, but who became HPV DNA positive during follow up, were examined for antibodies to HPV capsids by enzyme linked immunosorbent assay. One group consisted of 15 young girls (with eight controls who remained HPV DNA negative) who were becoming sexually active and the other comprised 12 male (with five controls) and 35 female (with seven controls) heterosexual attenders of a sexually transmitted disease clinic who had had multiple sexual partners. RESULTS: The sexually inexperienced girls showed IgA and IgG responses, but seldom an IgM response to infection with HPV types 6/11, 16, and 18. No consistent pattern of serological reactivity was apparent for the heterosexuals with multiple partners. The lack of association between current HPV DNA positivity and detectable antibodies in these individuals was possibly related to the duration of infection or to prior exposure to HPV. For the latter group serological reactivity to HPV capsids was significantly greater in women than in men (p = 0.001, p = 0.003, and p = 0.024, for IgG to HPV 6, 11, and 16, respectively). CONCLUSION: The sex difference in antibody response detected in previous studies with assays based on peptide antigens was thus corroborated in the present study with capsid based serological assays. This sex difference might reflect a difference in sexual activity and prior exposure to HPV between men and women in this particular group.

Adult↗

PubMed1998

Combined effect of smoking and human papillomavirus type 16 infection in cervical carcinogenesis.

To study the combined effect of smoking and human papillomavirus (HPV) type 16 infection in high-grade cervical intraepithelial neoplasia, we analyzed data from a Norwegian population-based case-control study including 90 patients and 216 controls, 20-44 years of age. We assessed HPV-16 status both by polymerase chain reaction detecting virus DNA and by enzyme-linked immunosorbent assay detecting antibodies against virus capsid. Smoking was associated with cervical intraepithelial neoplasia grade II-III in HPV-16-positive individuals. Using the jointly unexposed (HPV-16 DNA-negative never-smokers) as the reference group, we determined the risk of cervical intraepithelial neoplasia grade II-III in HPV-16 DNA-positive never-smokers and HPV-16 DNA-positive ever-smokers (odds ratio = 15.7; 95% confidence limits = 3.2, 76.5, and odds ratio = 65.9; 95% confidence limits = 22.3, 194.3, respectively). The estimated proportion of cases among HPV-16-positive smokers that is attributable to the interaction between the two causes is 74%, based on HPV-16 DNA positivity.

Adult↗

PubMed1997

A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway.

Infection with the human papillomavirus (HPV), notably HPV type 16, has been associated with esophageal cancer in seroepidemiological studies. To evaluate the consistency of the association, we performed a nested case-control study of HPV seropositivity and risk of esophageal cancer within a prospectively followed cohort of 300,000 Norwegian men and women who had donated blood samples to a serum bank. The data file of the serum bank was linked with the nationwide Cancer Registry of Norway to identify esophageal cancers diagnosed after donation of the serum sample. Fifty-seven cases and 171 matched controls were analyzed for antibodies to specific microorganisms, and odds ratios for developing esophageal cancer were calculated. There was an increased risk of developing esophageal cancer among HPV 16-seropositive subjects (odds ratio = 6.6; 95% confidence interval, 1.1-71) but not among Chlamydia trachomatis-seropositive subjects. Adjustment for the presence of serum cotinine, a marker of smoking habits, did not affect the estimates substantially. The seroepidemiological association between HPV 16 and esophageal cancer seems to be consistent in different countries.

Adult↗

PubMed1997

Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers.

OBJECTIVE: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. DESIGN: Data from two large serum banks to which about 700,000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. SUBJECTS: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. MAIN OUTCOME MEASURES: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. RESULTS: Subjects seropositive for human papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio infinity (3.8 to infinity)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. CONCLUSIONS: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers.

Adult↗

PubMed1997

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

Adenocarcinoma↗

PubMed1997

[Sexuality and STD infections among teenage girls. "Unprotected sex" is common in spite of sufficient knowledge about the risks].

A 2-year prospective study of sexual behaviour transmitted diseases (STDs) in 98 healthy 16-year-old schoolgirls showed human papillomavirus (HPV) infections to have spread rapidly among sexually active girls, whereas none of the virgins manifested HPV DNA in the cervix or anti-HPV 16 or anti-HPV33 antibodies in serum. A high level of knowledge of STDs and their prevention failed to induce appropriate behaviour among the sexually active.

Adolescent↗

PubMed1997

Identification of a cytotoxic T-lymphocyte epitope in the human papillomavirus type 16 E2 protein.

Persistent infection with oncogenic types of human papillomaviruses (HPV) is the major cause of cervical cancer precursor lesions. Cellular immune responses are considered important in the elimination of HPV infection, but the targets are not well defined. HPV E1 and E2 proteins form a replicative complex necessary for viral genome maintenance. To investigate whether epitopes in the E1 or E2 proteins can serve as targets for cytotoxic T-lymphocyte (CTL)-mediated killing, we identified peptides containing the human leukocyte antigen (HLA)-A*0201 binding motif in the deduced amino acid sequences of the HPV-16 E1 and E2 genes. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to elicit peptide-specific CTLs from healthy blood donors. We found one peptide from the E1 and one from the E2 protein sequence that were capable of eliciting peptide-specific CTLs. The E2-specific CTLs lysed an HPV-16-transfected cervical carcinoma cell line, but not the untransfected HPV-negative parental cell line, indicating that the identified E2 epitope can be presented to CTLs in HPV-positive epithelial cells. These findings might have potentially important implications for studies of the natural history of HPV infection in relation to cervical carcinogenesis.

Amino Acid Sequence↗

PubMed1997

A monoclonal antibody against intact human papillomavirus type 16 capsids blocks the serological reactivity of most human sera.

A type-specific and neutralizing mouse MAb (V5) against human papillomavirus (HPV) type 16 capsids was found to block the serological reactivity of human sera with the corresponding capsids. Out of 352 human serum samples tested for the presence of IgG against HPV-16, more than 75% of reactive sera were completely blocked by the V5 antibody. Type-specific MAbs against HPV-6, -18 and -33 were also found to block serological reactivity with capsids of the corresponding HPV types for the majority of reactive human sera. The results suggest that most antibodies in human sera that are reactive with intact HPV capsids recognize the same or closely related major antigenic determinant(s).

Adolescent↗

PubMed1997

Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease.

Identification of in vitro immunogenic T-cell epitopes is important for the design of immunotherapeutics targeted to specific antigenic sites. To identify candidate cytotoxic T-lymphocyte (CTL) epitopes in the protease of human immunodeficiency virus type 1 (HIV-1) strain MN, we synthesized 9-mer and 10-mer peptides containing the HLA-A*0201 binding motif. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to stimulate primary CTLs from healthy HIV-negative blood donors. Peptide-specific CTLs were obtained from five out of six donors by stimulation with a 9-mer (LVGPTPVNI) or a 10-mer (VLVGPTPVNI) peptide derived from a highly conserved amino acid stretch in the C-terminal region of the protease. Addition of peptide-specific CTLs to acutely HIV-infected lymphocytes resulted in inhibition of p24gag production. In conclusion, a highly conserved HIV protease peptide regularly elicits peptide-specific CTLs. Targeting immune responses against defined epitopes in non-variable regions may be a feasible way to minimize the risk of virus escape from immune surveillance.

Cells, Cultured↗

PubMed1997

Antibodies against human papillomavirus type 6 capsids are elevated in men with previous condylomas.

Serum samples from 47 men with current condylomas, 32 men with a history of condylomas and from 205 men with no history of genital wart disease, who were attending sexually transmitted disease (STD) clinics at two different hospitals in Stockholm, were analyzed for the presence of immunoglobulin G (IgG) and A (IgA) antibodies to capsids of human papillomavirus types 6 and 11. IgG to HPV type 6 was found among 35% of patients with a history of condylomas compared to 10% of controls (p = 0.0003), but only among 27% of patients with current condylomas. Antibodies to HPV 6 and to HPV 11 showed a very limited correlation, suggesting that the antibodies are HPV-type restricted. The results strengthen conclusions from a previous serological study indicating that IgG antibodies against HPV 6 develop late during condylomatous disease and mostly reflect previous exposure to the virus.

Antibodies, Viral↗

PubMed1997

Seropositivity against HPV 16 capsids: a better marker of past sexual behaviour than presence of HPV DNA.

OBJECTIVES: To assess if seropositivity to human papillomavirus type 16 capsids is a better marker of sexual history than the presence of HPV DNA. STUDY DESIGN: A population based age stratified random sample of 234 Norwegian women (mean age 32.8 years, range 20-44) was examined for HPV serum antibodies, cervical HPV DNA, cytology and age in relation to sexual behaviour. RESULTS: Neither age nor age at first sexual intercourse was associated with HPV 16 antibodies. Adjusted ORs for 4-5; 6-10 and > 10 versus 0-1 lifetime sexual partners, were 13.1 (95% CI 1.5-110.8), 8.2 (1.0-69.6) and 10.5 (1.2-94.0) for HPV 16 seropositivity, respectively; and 2.6 (0.2-27.8), 3.4 (0.4-31.7) and 4.1 (0.4-42.8) for HPV 16 DNA positivity, respectively. CONCLUSION: Seropositivity to HPV 16 capsids is positively associated with the number of sexual partners, suggesting that HPV 16 is predominantly sexually transmitted. The fact that serology had a stronger association with number of sexual partners than viral DNA suggests that seroreactivity is a better measure of lifetime history of HPV infection.

Adult↗

PubMed1997

Evidence for at least two distinct groups of humoral immune reactions to papillomavirus antigens in women with squamous intraepithelial lesions.

Serological markers of squamous intraepithelial lesions (SILs), the precursors of cervical cancer, have not been studied extensively. To screen for antibody responses that might be associated with SILs, we measured IgG and/or IgA to nine antigens based on papillomaviruses, the infectious cause of SIL and cervical cancer, using an ELISA format. Cases were 59 women with low grade SIL (LSIL) and 38 with high grade SIL (HSIL). Controls were 50 women chosen to minimize the possibility that they ever had SILs [individuals who had no history of SIL and repeatedly tested negative for cervical human papillomavirus (HPV) DNA], frequency age-matched to cases. The data showed that five antibodies had strong positive associations with SILs and that one was inversely related to SILs. By studying these antibodies in pairs, furthermore, we found that case-control differences were enhanced. In particular, the combination of IgG to an epitope in the E6 protein of HPV 16 (E6:10) and IgA to HPV 16 virus-like particles (VLPs) was detected in 53% of LSILs and 65% of HSILs but only 9% of controls. These same responses were both negative in just 6% of LSILs and zero HSILs, compared to 59% of controls. Notably, E6:10 IgG and HPV 16 VLP IgA were not correlated with each other, and the other antibody responses positively associated with SILs could be broken into two groups: those correlated with E610 IgG and those correlated with HPV 16 VLP IgA. Overall, the data suggest that several papillomavirus antibodies may be strongly related to SILs, and that they can be divided into at least two independent groups of humoral immune reactions.

Antibodies, Viral↗

PubMed1997

Human papillomavirus antibody responses among patients with incident cervical carcinoma.

The human papillomavirus (HPV) is recognized as a major cause of cervical cancer precursor lesions. HPV serology is a key method in the continuing elucidation of the importance of HPV exposure for cancer development and in predicting HPV-associated diseases. To extend previous HPV serological studies on cervical cancer, serum samples from a consecutive series of 216 women with incident untreated cervical carcinoma and 243 age- and sex-matched healthy blood donors were evaluated for the presence of antibodies against HPV capsids, a marker of past or present HPV exposure, as well as against several cervical cancer-associated defined HPV epitopes. Among the capsid antibody responses, HPV type 16 seropositivity had the strongest association with cervical cancer (OR 2.7, 95% CI 1.8-4.2), but HPV 18 and HPV 33 seropositivities were also significantly associated with cervical cancer (OR 1.6, 95% CI 1.1-2.5; and OR 1.5, 95% CI 1.0-2.2, respectively). The antibody responses against the defined HPV epitopes were confirmed to be associated with cervical cancer, at ORs ranging from 1.4 to 2.0. In conclusion, the study confirms that antibodies against defined HPV epitopes are associated with cervical cancer and provides evidence that seropositivities for HPV types 16, 18, and 33 are associated with cervical cancer risk.

Adult↗