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J Dillner

Publications and source records attributed to J Dillner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Immunity to oncogenic human papillomaviruses.

UNLABELLED: The establishment of human papillomavirus (HPV) infection as a major cause of several human cancer forms, notably cervical cancer, has spurred development of prophylactic and/or therapeutic HPV vaccines for prevention of cervical neoplasia. Knowledge of the immunity to HPV forms the basis for such endeavors. METHOD: A literature review of humoral and cellular immunity to HPV. The overview on human leukocyte antigen (HLA) and cervical cancer was expanded to a formal metaanalysis, where relevant articles were located by Medline search and citation analysis and graded by preassigned quality criteria on study design. RESULTS: The antibody response to the HPV particle is dominated by a neutralizing antibody response to a typespecific, conformationally dependent immunodominant epitope. Vaccines based on viral particles lacking the viral genome (virus-like particles, VLPs) have been highly successful in preventing and treating HPV infection in several animal model systems. In humans, the serum antibody response to VLPs is stable over time, also after the HPV infection has been cleared, resulting in HPV serology being used as a marker of cumulative HPV exposure in spite of the fact that a significant proportion of HPV-exposed subjects fail to seroconvert. More than 90% of HPV infections will clear spontaneously. The factors that determine whether an HPV infection is cleared or persists and increases the risk for cancer are not known, but cellular immunity is implicated. Several HLA class II haplotypes are associated with cervical cancer: DQw3 increases and DR13 decreases the risk for cervical cancer in general (odds ratios (OR) and 95% confidence intervals (CI): 1.25(1.15-1.37) and 0.69 (0.56-0.85), respectively); DR15 increases the risk for HPV16-carrying cancer (OR: 1.47; CI: 1.20-1.81); and DR7 may be either protective or increase the risk. Most cervical cancers have downregulated the expression of at least one HLA class I antigen, whereas class II expression is increased in infected epithelium. A Th2 cytokine profile is associated with progression to cervical cancer. HPV-antigen-specific proliferative responses have been detected in many studies, although it is not entirely clear whether these responses are HPV type specific or may be cross-reactive between HPV types. Specific cytotoxic T lymphocyte (CTL) responses were originally reported in only a minority of infected subjects, typically cancer patients, but with advancing technology, specific CTLs can be stimulated from about half of the women with HPV-carrying disease. In animal model systems, CTL responses can mediate clearance. CONCLUSION: The antibody response to HPV is a mediator of type-specific protective immunity, which forms the basis for prophylactic vaccine candidates. The cellular immunity to HPV is implicated as an important factor in cervical carcinogenesis, but the main targets and types of responses that mediate HPV clearance are not established.

Antibodies, Viral↗
PubMed2001

Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer.

Human papillomaviruses type 16 and 18 are the major cause of cervical cancer. However, genetic factors contribute to the propensity of persistent HPV infection and cervical carcinoma. Allelic variants of the human leukocyte genes have shown to be associated with cervical neoplasia. The strongest associations have been found with the genes in the HLA class II region. The aim of this study was to analyze the association of two non-HLA class II markers with invasive cervical cancer. Microsatellite polymorphism of the TNFA gene located in the class III region and a short tandem repeat polymorphism of the MICA gene located in the centromeric end of the HLA class I region were analyzed. Eighty-five patients and 120 matched control individuals from a population-based cohort from Northern Sweden participated in this nested case-control study. MICA was not associated with cervical carcinoma. TNFa-11 frequency was increased in the HPV18 DNA positive patients (OR = 2.84, p = 0.0481, CI = 1.04-7.78, pc = NS). TNFa-11 was not associated with susceptibility to HPV16 infection, but it increased the risk for cervical cancer with the HLA DQ6 (DQA 1*0102-DQB 1*0602) haplotype. Our findings indicate that the association of TNFA with cervical cancer is different with CIN. The extended HLA DQ6-TNFa-11 haplotype is increasing the risk for development of cervical cancer significantly (OR = 3.08, p = 0.0104, CI = 1.30-7.31).

Adult↗
PubMed2001

Human papillomavirus infection, risk for subsequent development of cervical neoplasia and associated population attributable fraction.

BACKGROUND: Human papillomavirus (HPV) is the major cause of cervical neoplasia but estimates of the population attributable fraction (PAR%), of HPV vary. PAR% has not been derived from longitudinal studies although assessment of HPV exposure prior to the neoplasia diagnosis should increase validity of such estimates. AIMS: Systematic review and meta-analysis of longitudinal studies on HPV associated relative risk (RR) for and PAR% of HPV16 in cervical neoplasia. METHODS: Pertinent data from longitudinal studies was made available through Medline and substituted by various hand searches. HPV associated weighted mean RR, with 95% confidence interval (CI) of cervical neoplasia, and the PAR% of HPV16 in cervical carcinoma were estimated both for unselected and low HPV prevalence populations. RESULTS: HPV associated RR of cervical carcinoma in PCR-based studies was 17 (95% CI 8.2-33). HPV16 associated RRs in seroepidemiological studies were 3.3 (95% CI 2.2-4.9) for the unselected population, HPV16 seroprevalence 11.0%, and 12.5 (95% CI 5.5-29) for a population with low HPV16 seroprevalence of 5.3%. Corresponding PAR% estimates of HPV16 were 27 and 44%, respectively. CONCLUSION: Protective vaccination against HPV16 infection would prevent up to 44% of cervical carcinoma.

Case-Control Studies↗
PubMed2001

Primary screening for human papillomavirus infection.

As human papillomavirus infection is now known to be a necessary risk factor for at least 95% of cervical cancers, the medical community has a responsibility to assess and evaluate how this knowledge should best be used for the prevention of cervical cancer. Organized screening strategies combining cytological screening with human papillomavirus testing in older age groups could theoretically be more sensitive than current screening programmes in reducing the incidence of cervical cancer. If it is possible safely to extend the screening interval in human papillomavirus-negative women, such programmes could also both be more effective and more cost-efficient. Although some modelling studies have indicated that this could indeed be the case, evidence from clinical trials evaluating the long-term protective effect of primary human papillomavirus screening is still lacking. The key issues on the research agenda for primary human papillomavirus screening are reviewed.

Female↗
PubMed2001

Poor antibody response against human papillomavirus in adult-onset laryngeal papillomatosis.

To investigate whether adult-onset laryngeal papillomatosis induces serum antibodies to the human papillomavirus (HPV), 60 patients underwent a clinical examination, and HPV DNA from their laryngeal biopsy was assayed by PCR and HPV serology with virus-like particles as the antigen. Patients and controls (n = 53) showed no differences in their HPV 6 and 16 antibodies. Patients more often had HPV 11 antibodies, female patients more often than female controls or male patients. Of the female patients, 5 of 15 had a history of genital condylomas and, at the follow-up visit, 5 of 9 had cervical cytology consistent with genital HPV infection. The fact that HPV antibodies did not correlate with clinical features of the laryngeal disease or with HPV DNA detected in the larynx, suggests that HPV antibodies in female patients were induced by genital rather than laryngeal HPV infection. The high prevalence of abnormal Pap smears indicates that gynaecological examination of female adult-onset laryngeal papilloma patients is warranted.

Age of Onset↗
PubMed2001

Viral load of human herpesvirus 8 in peripheral blood of human immunodeficiency virus-infected patients with Kaposi's sarcoma.

Viral load is an important marker of activity of viral diseases for a number of viruses. We wished to evaluate whether the viral load of human herpesvirus 8 (HHV-8) in peripheral blood was a consistent feature of Kaposi's sarcoma (KS) patients and whether the viral load correlated with human immunodeficiency virus (HIV) RNA levels, CD4 counts, and/or the HHV-8 seroreactivity. Fifty-four consecutive plasma samples from 14 patients with KS were evaluated for HHV-8 viral load by quantitative real-time PCR. Samples were analyzed at the start of highly active antiretroviral therapy (HAART) and at different intervals during treatments. The median HHV-8 DNA load before HAART treatment was 8,998 (ranging from 170 to 40,100) copies/ml and 12,270 (ranging from 40 to 142,575) copies/ml during HAART. There were both increasing and decreasing trends. There was an association between HHV-8 DNA and HIV RNA viral loads (odds ratio [OR] = 5.40; 95% confidence interval [95% CI], 1.54 to 18.98) and between HHV-8 viral load and CD4 cell counts (OR = 7.24; 95% CI, 1.30 to 40.35). High HHV-8 viral load was also correlated with the titers of antibodies to the lytic HHV-8 antigen detected with immunofluorescence (P < 0.01), but not with antibodies to the latent HHV-8 antigen. In conclusion, we found that HHV-8 viremia in KS is associated with HIV viral load, CD4 cell counts, and lytic HHV-8 serological reactivity. HHV-8 viral load monitored by real time PCR might be useful for determination HHV-8 viral load during the follow-up of KS patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Seropositivity to human herpesvirus 8 in relation to sexual history and risk of sexually transmitted infections among women.

The mode of transmission of human herpesvirus 8 (HHV8) was investigated in two seroepidemiological studies of Swedish women who completed a questionnaire about sexual behavior. Seropositivity for HHV8 antibodies, measured using an indirect immunofluorescence assay, was linked to a high number (>10) of sexual partners (P < 0.004). It also correlated strongly with a history of other sexually transmitted diseases (STD; P < 0.0001), in particular with a history of Chlamydia trachomatis infection and condyloma acuminata. There was appreciable HHV8 seropositivity already among virginal or monogamous women (9%). In summary, HHV8 transmission to women in Sweden may occur nonsexually. When sexual transmission occurs, it appears to be associated with high risk-taking sexual behavior.

Adolescent↗
PubMed2000

Seroepidemiology of human papillomavirus type 73: a sexually transmitted low-risk virus.

Human papillomavirus type 73 (HPV 73) has been detected in some invasive cervical cancers and has been cloned from a squamous-cell carcinoma of the esophagus, but the epidemiology of this infection and its associated risk of cancer is unknown. We investigated the seroepidemiology of this virus using virus-like particles. The IgG response to HPV 73 appeared to be HPV type-specific, since a comparison of HPV 73 antibody levels before and after infection with HPV 6, 11, 16, 18 or 33 found no evidence of cross-induction of HPV 73 antibodies and since there was little correlation between the antibody levels to HPV 73 and the other 5 investigated HPV types. In both a cross-sectional serosurvey that included 274 women and a 7-year follow-up study that enrolled 98 women, HPV 73 seropositivity was found to be strongly dependent on the number of lifetime sexual partners [OR for > 4 vs. 0 to 1 partners: 6.0 (95%CI: 1.4-53.6) and 7.9 (95% CI: 2.8-28.3), respectively]. Finally, the risk for HPV 73 seropositive women to develop CIN was investigated in a prospective study nested in a cohort of 15,234 Swedish women. The population-based HPV 73 seroprevalence in Sweden was 14%. No excess risk for CIN was found (OR: 0.77). We conclude that HPV 73 is a mainly sexually transmitted, probably mostly transient, infection that does not confer any measurably increased risk for CIN development.

Adult↗
PubMed2000

Chlamydia trachomatis infection as a risk factor for invasive cervical cancer.

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.

Adenocarcinoma↗
PubMed2000

Cervical cancer screening in Sweden.

Organised cervical cancer screening was implemented in Sweden in the mid-1960s. A marked decline in cervical cancer incidence could be attributed to the time-point of start of screening. Squamous cell carcinoma has declined by 60%, whereas adenocarcinoma has increased. About 950000 papanicolaou (Pap) smears are taken annually. Only 31% of the smears taken in the organised screening programme. As of 1998, the screening guidelines are 3-yearly tests between 23 and 50 years of age and 5-yearly tests between 50 and 60 years of age. The article reviews the screening practise in Sweden, the current efforts to improve the quality of the screening programme, as well as the ongoing randomised evaluations of organised primary screening for cervical human papilloma virus (HPV) infection.

Adult↗
PubMed2000

Trends over time in the incidence of cervical neoplasia in comparison to trends over time in human papillomavirus infection.

INTRODUCTION: The establishment of human papillomavirus (HPV) infection as a major cause of cervical neoplasia has resulted in major efforts to develop prophylactic HPV vaccines for prevention of cervical neoplasia. Cervical cancer and the other HPV-associated cancers constitute a major public health burden and eradication of the major causative infection is certainly the most appealing long-term preventive measure. Nevertheless, the effects of preventive HPV vaccination will need to be estimated and compared for (cost-) efficacy with other primary prevention and with secondary prevention programs. However, estimating the effects of preventing a causative exposure is complicated when the exposure is a transmissible infection. The spread of the epidemic is dynamic and may change over time depending e.g. on the changes in human behavior. Depending on the circumstances, prevention of an infection may have either greater or lesser effects than the prevention of a non-infectious exposure. Estimating the time trends in HPV infections and the underlying trends in the risk of cervical neoplasia is important for estimating effects of interventions. METHOD: A literature review on recent evidence on time trends in cervical neoplasia, compared with evidences on time trends in HPV infections and interactions between different types of HPV infections. RESULTS: In Finland, there has between 1991 and 1995 been a 60% increase in the incidence of cervical cancer among women <55 years of age. Trends in detection rates of cervical cancer precursor lesions are consistent with an increase in the background cervical cancer risk. From the 1960s to 1980s, there has been a major increase in HPV seroprevalences over time in the Nordic countries. Increasing trends are also seen for other sexually transmitted diseases and smoking. Several studies indicate the existence of interaction between benign and oncogenic HPV types, thus making the relationship between the incidences in HPV infections and in cervical neoplasia complex. CONCLUSION: The increase in cervical cancer is paralleled by increases in HPV infection, other STDs and smoking and changes in screening practices, all of which may have contributed. Prediction of the effect on cervical cancer incidence of changes in HPV incidences is complicated by the existence of several risk factors, the protective effect of screening and by the population dynamics of HPV infections.

Age Factors↗
PubMed2000

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.

Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.

Adult↗
PubMed2000

A population-based five-year follow-up study of cervical human papillomavirus infection.

OBJECTIVE: The purpose of this study was to determine the long-term tendency for cervical human papillomavirus infections to persist in the general population. STUDY DESIGN: From 500 women who participated in a 1991 population-based survey, 90 healthy women with normal results of cytologic examination (women with human papillomavirus deoxyribonucleic acid detected and age-matched control women without human papillomavirus deoxyribonucleic acid detected) were interviewed and examined 5 years later colposcopically, cytologically, and with human papillomavirus serologic testing and human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction with 2 different consensus primer pairs (MY09 and MY11 and GP5(+) and GP6(+)), type-specific polymerase chain reaction, and deoxyribonucleic acid sequencing. RESULTS: The 5-year human papillomavirus clearance rate was 92%. Only human papillomavirus type 16 infections persisted. Colposcopic impression of grade 2 cervical intraepithelial neoplasia was associated with persistent human papillomavirus 16 infection (P <.03). Human papillomavirus detection was associated with sexual history. Human papillomavirus type was the only determinant of human papillomavirus persistence. CONCLUSION: The high clearance rates in a population-based setting with a 5-year follow-up period imply that inclusion of human papillomavirus deoxyribonucleic acid testing in population-based cervical screening programs should target persistent infection.

Adult↗
PubMed2000

Regular disappearance of the human papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser.

OBJECTIVE: We wished to evaluate the effectiveness of treatment of cervical dysplasia by laser conization in relation to persistence of human papillomavirus after treatment. STUDY DESIGN: Of 203 women referred to colposcopy because of an abnormal Papanicolaou smear, 149 women could be followed up for 3 years. A total of 108 women were treated by carbon dioxide laser excision, 4 women were treated by carbon dioxide laser evaporation, and 37 women were merely followed up. Cervical samples were taken before treatment and at follow-up 3 years later and were analyzed by nested general primer polymerase chain reaction for human papillomavirus deoxyribonucleic acid. RESULTS: Among women treated by laser conization, 82 (73.2%) had positive results for human papillomavirus deoxyribonucleic acid before treatment. Three women (2.7%) had a positive finding at follow-up, but no woman had the same human papillomavirus type on both occasions. Eighty-eight women had grade 1 to grade 3 cervical intraepithelial neoplasia before treatment, whereas during follow-up only 2 squamous cells atypias were found. CONCLUSION: The human papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human papillomavirus should be favored.

Adult↗
PubMed2000

Etiology of squamous cell carcinoma of the penis.

OBJECTIVE: To review the epidemiology of invasive cancer of the penis based on scientific publications identified by a Medline search from 1966-2000 for the keywords penis/penile, cancer/carcinoma and risk as well as the cited references in the identified papers. RESULTS: Strong risk factors (OR >10) identified by case-control studies included phimosis, chronic inflammatory conditions such as balanopostitis and lichen sclerosus et atrophicus and treatment with psoralen and ultraviolet A photochemotheraphy (PUVA). A consistent association was found between penile cancer and smoking that was dose-dependent and not explained by investigated confounding factors such as sexual history. Sexual history and self-reported history of condyloma were associated with a 3-5-fold increased penile cancer risk. Cervical cancer in the wife was not consistently associated with cancer of the penis in the husband. Circumcision was associated with penile cancer risk in ecological studies. In a case-control study, circumcision neonatally, but not after the neonatal period, was associated with a 3-fold decreased risk, albeit 20% of penile cancer patients had been circumcised neonatally. In a large number of case series, human papillomavirus (HPV) DNA was identified in penile neoplastic tissue. In penile intraepithelial neoplasia, between 70 and 100% of lesions were HPV DNA positive, whereas invasive penile cancer was positive in only 40-50% of cases. A few serological case-control studies and one prospective study also identified an association between HPV type 16 and penile cancer risk. An association between penile cancer risk and HPV prevalence in the population was also suggested by ecological studies. CONCLUSION: The evidence on risk factors for penile cancer suggests that preventive measures that could be considered include prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and prophylactic prevention of HPV infection.

Carcinoma in Situ↗
PubMed2000

Type specificity and significance of different isotypes of serum antibodies to human papillomavirus capsids.

Isotype-specific serum antibody responses against human papillomavirus (HPV) type 16 were evaluated by use of cross-sectional, prospective, and population-based seroepidemiologic studies. IgG1 and IgA were the most abundant isotypes. No sample contained IgG2, and <25 samples contained IgG3 or IgM. Total IgG, IgA, and IgG1 were HPV type specific and were associated with HPV-16 DNA (odds ratios [ORs], 5.4, 5.0, and 5.9, respectively; P<.001) but not with other HPV DNA (ORs, 1.2, 1.2, and 0.8, respectively; P value was not significant). Total IgG and IgG1 were strongly associated with number of lifetime sex partners (P<.001); IgA was only associated with number of recent sex partners and lifetime sex partners among younger women. Total IgG, IgG1, and IgA were associated with cervical intraepithelial neoplasia type III and also predicted risk of future cervical neoplasia. IgG and IgG1 appeared to mark lifetime cumulative exposure, whereas IgA may mark recent or ongoing infection.

Adolescent↗
PubMed2000

Seropositivity to multiple sexually transmitted infections is not common.

BACKGROUND: Seropositivity for several sexually transmitted infections (STIs) is often used as a surrogate measure of sexual behavior. The authors assessed the concomitant seropositivity for STIs in women. GOAL: To estimate the excess of concomitant seropositivity for four STIs among fertile-aged women assuming no coinfections above what would be expected at random. STUDY DESIGN: Antibodies to herpes simplex virus type 2, human papillomavirus type 16, HIV, Chlamydia trachomatis, and Treponema pallidum were determined from a random sample of 1110 pregnant women in Tallinn, Estonia. RESULTS: A total of 310 combinations of the concomitant seropositivity were observed, whereas only 193 were expected by chance. Among persons seropositive for two STIs, 78 extra combinations were observed, whereas for three STIs, 35 extra combinations were observed. For four STIs, 3.8 extra combinations were found. CONCLUSIONS: Seropositivity to multiple STIs is not common. This fits the concept of different transmission probabilities and the spread of the STIs, and suggests that seropositivity alone should be used with caution as a surrogate to sexual behavior in women.

Adolescent↗