Seroprevalence of HPV vaccine types 6, 11, 16 and 18 in HIV-infected and uninfected women from Brazil.

BACKGROUND: Information on vaccine-type HPV seroprevalence is essential for vaccine strategies; however, limited data are available on past exposure to HPV-quadrivalent vaccine types in HIV-infected woman in Brazil. OBJECTIVES: To assess the seroprevalence for HPV types 6, 11, 16 and 18 in HIV-infected and uninfected women, from Rio de Janeiro, Brazil and to investigate potential associations with age and pregnancy status. STUDY-DESIGN: 1100-sera were tested by virus-like particle (VLPs)-based ELISA for antibodies to HPV types 16, 18, 6 and 11. Statistical analysis was carried out by STATA/SE 10.1 and comparisons among HIV-infected and HIV-uninfected women were assessed by Poisson regression models with robust variance. RESULTS: HPV-6, 11, 16 and 18 seroprevalence was significantly higher among HIV-positive women (29.9%, 8.5%, 56.2% and 38.0%, respectively) compared to HIV-negative women (10.9%, 3.5%, 30.8% and 21.7%, respectively), when adjusted by age and pregnancy status. Overall, 69.4% of HIV-infected and 41.5% of HIV-uninfected women tested positive for any HPV quadrivalent vaccine type. However 4.7% and 1.1%, respectively, tested positive for all HPV vaccine type. In HIV-uninfected women who were pregnant, we found a higher HPV-11 seroprevalence (8.5% vs. 1.5%; P < 0.001) and a lower HPV 16 seroprevalence (22.6% vs. 34.2%; P = 0.010) compared to not pregnant women. HIV-uninfected women, aged 40 or more years old had a higher HPV 16 seroprevalence compared to women aged less than 40 years old. CONCLUSIONS: We did not observe a strong association between age and positive HPV antibodies nor an association between pregnancy and HPV seroprevalence. HPV seroprevalence was significantly higher among HIV-infected women compared to HIV negative women. In both populations the seroprevalence to all four HPV vaccine types was low suggesting that women may potentially benefit from the HPV vaccines.

longitudinal analysis of levels of immunoglobulins against BK virus capsid proteins in kidney transplant recipients.

This study sought to evaluate serology and PCR as tools for measuring BK virus (BKV) replication. Levels of immunoglobulin G (IgG), IgM, and IgA against BKV capsids were measured at five time points for 535 serial samples from 107 patients by using a virus-like particle-based enzyme-linked immunosorbent assay. Viral DNA in urine and plasma samples was quantitated. The seroconversion rate was 87.5% (14/16); 78.6% (11/14) and 14.3% (2/14) of patients who seroconverted developed viruria and viremia, respectively. Transient seroreversion was observed in 18.7% of patients at 17.4 +/- 11.9 weeks posttransplant and was not attributable to loss of antigenic stimulation, changes in immunosuppression, or antiviral treatment. Titers for anti-BK IgG, IgA, and IgM were higher in patients with BKV replication than in those without BKV replication. A rise in the optical density (OD) of anti-BK IgA (0.19), IgM (0.04), or IgG (0.38) had a sensitivity of 76.6 to 88.0% and a specificity of 71.7 to 76.1% for detection of viruria. An anti-BK IgG- and IgA-positive phenotype at week 1 was less frequent in patients who subsequently developed viremia (14.3%) than in those who subsequently developed viruria (42.2%) (P = 0.04). Anti-BK IgG OD at week 1 showed a weak negative correlation with peak urine viral load (r = -0.25; P = 0.05). In summary, serial measurements of anti-BKV immunoglobulin class (i) detect onset of viral replication, (ii) document episodes of seroreversion, and (iii) can potentially provide prognostic information.

Seroprevalence and risk factors for human papillomavirus in Taiwan.

The aim of the study was to tailor a future Human papillomavirus (HPV) vaccine campaign and to help perform early primary prevention of HPV infection in Taiwan, where the incidence of cervical cancer is high. A cross-sectional survey was conducted of 826 female students, ages 10, 13, 16 and 19-22 years. A self-administered questionnaire was used to collect information on risk factors for HPV infection. Serum samples were tested for antibodies to HPV 16 capsids using a virus-like particle-based enzyme-linked immunosorbence assay. The age-adjusted odds ratio of HPV seropositivity was calculated for each risk factor by multiple logistic regression analysis. HPV 16 antibodies were detected in 13 (1.6%) of 826 participants. The HPV 16 seroprevalence was 0.35% (1/287), 0.85% (2/235), 3.2% (6/185) and 3.4% (4/119), respectively, for age groups of 10, 13, 16 and 19-22 years. In the multiple regression analysis, the history of having sexual activity was the most significant risk predictor for HPV 16 seropositivity. The seroprevalence of HPV 16 increased dramatically among high school seniors and university students, and was significantly associated with sexual activity. Vaccination against HPV is suggested to be undertaken in early adolescence, before 16 years of age and prior to sexual debut.

Prevalence of serum antibodies to human papilloma virus in patients with genital ulcer disease in an urban population of Tanzania.

BACKGROUND: The epidemiology of human papillomavirus (HPV) in Tanzania is largely unknown both in risk groups and in the general population. OBJECTIVE: To determine the cumulative seroprevalence of selected HPV types in order to evaluate exposure to HPV in urban Tanzania. METHOD: In a cross-sectional study, sera of 200 patients of both sexes with genital ulcer disease (GUD) and sera of 60 male blood donors and 60 pregnant women were tested for antibodies to the oncogenic HPV types 16, 18, 31, 33, 35, 51 and 52 using an ELISA based on virus-like particles (VLP). RESULTS: The overall seroprevalence of HPV types for all patients with GUD was 83% and 77% for women and men, respectively. For pregnant women and male blood donors, the corresponding percentages were 55% and 15%, respectively. The most common HPV types were 16, 18 and 52. Infection with multiple types was more than 10 and 5 times more frequent than infection with a single type 16 in patients with GUD and in pregnant women, respectively. The seroprevalence to HPV types 16, 18, 51 and 52 was considerably higher in HIV-positive patients with GUD than in HIV-negative patients. CONCLUSIONS: Infections with the oncogenic HPV types 16, 18 and 52 are common among patients with GUD and pregnant women in urban Tanzania, emphasising the need for control, treatment and implementation of appropriate HPV vaccine programmes.

Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica.

Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in Guanacaste, Costa Rica. Serologic responses to HPV-16 were measured in 7986 women by VLP-based enzyme-linked immunosorbent assay at both study enrollment (1993/94) and at 5-7 years of follow-up. Seropositive women were defined as >/=5 standard deviations above the mean optical density obtained for studied virgins at enrollment (n=573). Seroconnversion (n=409), persistence (n=675), and clearance (n=541) were defined based on enrollment and follow-up serology measurements. Age-specific distributions revealed that HPV-16 seroconversion was highest among 18- to 24-year-old women, steadily declining with age; HPV-16 seropersistence was lowest in women 65+ years. In age-adjusted multivariate logistic regression models, a 10-fold risk increase for HPV-16 seroconversion was associated with HPV-16 DNA detection at enrollment and follow-up; two-fold risk of seroconversion to HPV-16 was associated with increased numbers of lifetime and recent sexual partners and smoking status. Determinants of HPV-16 seropersistence included a 1.5-fold risk increase associated with having one sexual partner during follow-up, former oral contraceptive use, and a 3-fold risk increase associated with HPV-16 DNA detection at both enrollment and follow-up. Higher HPV-16 viral load at enrollment was associated with seroconversion, and higher antibody titres at enrollment were associated with seropersistence.

Poliovirus vaccination during pregnancy, maternal seroconversion to simian virus 40, and risk of childhood cancer.

Before 1963, poliovirus vaccine produced in the United States was contaminated with simian virus 40 (SV40), which causes cancer in animals. To examine whether early-life SV40 infection can cause human cancer, the authors studied 54,796 children enrolled in the US-based Collaborative Perinatal Project (CPP) in 1959-1966, 52 of whom developed cancer by their eighth birthday. Those children whose mothers had received pre-1963 poliovirus vaccine during pregnancy (22.5% of the children) had an increased incidence of neural tumors (hazard ratio = 2.6, 95% confidence interval: 1.0, 6.7; 18 cases) and hematologic malignancies (hazard ratio = 2.8, 95% confidence interval: 1.2, 6.4; 22 cases). For 50 CPP children with cancer and 200 CPP control children, the authors tested paired maternal serum samples from pregnancy for SV40 antibodies using a virus-like particle enzyme immunoassay and a plaque neutralization assay. Overall, mothers exhibited infrequent, low-level SV40 antibody reactivity, and only six case mothers seroconverted by either assay. Using the two SV40 assays, maternal SV40 seroconversion during pregnancy was not consistently related to children's case/control status or mothers' receipt of pre-1963 vaccine. The authors conclude that an increased cancer risk in CPP children whose mothers received pre-1963 poliovirus vaccine was unlikely to have been due to SV40 infection transmitted from mothers to their children.

A population based study of herpes simplex virus 2 seroprevalence in rural Costa Rica.

OBJECTIVES: To determine seroprevalence and determinants of herpes simplex virus 2 (HSV-2) seropositivity, in a random sample of a population based cohort of 10 049 women of Guanacaste, Costa Rica, using a highly sensitive and specific serological assay. METHODS: Seroprevalence was determined by a type specific HSV-2 ELISA assay in an age stratified random sample of 1100 women. Univariate and multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals for risk factors of seropositivity. RESULTS: Overall age adjusted HSV-2 seroprevalence was 38.5% (95% CI, 37.5 to 39.5), and it was strongly associated with increasing age (p(Trend<0.0001)), both among monogamous women and women with multiple sexual partners. A greater number of lifetime sexual partners increased the risk of seropositivity, with a 28.2% (95% CI, 24.4 to 32.2) seroprevalence among monogamous women and 75% (95% CI, 65.6 to 83.0) seroprevalence for those with four or more partners (OR = 7.6 95% CI, 4.7 to 12.4 p(Trend<0.0001)). Barrier contraceptive use was negatively associated with HSV-2 seropositivity (OR 0.54, 95% CI, 0.31 to 0.94). Women with antibodies against HPV 16, 18, or 31 were 1.6 times more likely to be HSV-2 seropositive (OR 1.6, 95% CI, 1.2 to 2.1). CONCLUSIONS: HSV-2 infection is highly endemic in Guanacaste, even among lifetime monogamous women, suggesting a role of male behaviour in the transmission of the infection. Until vaccination against HSV-2 is available, education to prevent high risk sexual behaviour and the use of condoms appear as preventive measures against HSV-2.

Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10000 women in Costa Rica.

Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n=9949), HPV-18 (n=9928), HPV-31 (n=9932), and HPV-45 (n=3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women.

Comparison of sequencing of the por gene and typing of the opa gene for discrimination of Neisseria gonorrhoeae strains from sexual contacts.

Typing of gonococcal strains is a valuable tool for the biological confirmation of sexual contacts. We have developed a typing method based on DNA sequencing of two overlapping por gene fragments generated by a heminested PCR. We compared sequencing of the por gene (POR sequencing) and typing of the opa gene (OPA typing) for the characterization of strains from 17 sexual partnerships. Both methods were highly discriminatory. A different genotype was detected in 15 of the 17 epidemiologically unconnected couples by POR sequencing and in 16 of the 17 couples by OPA typing with restriction enzyme HpaII. Within partnerships, identical genotypes were obtained from 16 of the 17 known sex contacts by POR sequencing and from 15 of the 17 by OPA typing. Compared to OPA typing, which relies on interpretation of bands in a gel, DNA sequence data offer the advantage of being objective and portable. As costs for sequencing decline, the method should become affordable for most laboratory personnel who wish to type gonococcal strains.

The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine.

Due to its role in the synthesis and repair of DNA, folate may protect against the development of cervical cancer. Prospective data on the possible association between folate and cervical cancer have been lacking. There is also a paucity of prospective evidence concerning the possible associations between cervical cancer and vitamin B12, which shares pathways with folate, and homocysteine, a marker of low B vitamin concentrations. A nested case-control study was conducted to prospectively evaluate the associations between cervical cancer and serum concentrations of folate, vitamin B12, and homocysteine. Among a community-based cohort of women who donated blood in 1974 for a serum bank in Washington County, Maryland, 39 cases of cervical cancer diagnosed between 1975 and mid-1990 were included in the study (13 cases of invasive cervical cancer and 26 cases of carcinoma in situ). Two controls were matched to each case by age, race, and sex. Stored serum from the cases and controls was assayed for folate, B12, and homocysteine concentrations. For folate, adjusted odds ratios were 1.0, 0.62, and 0.60 for the low to high thirds of the serum concentrations, respectively, a trend in the protective direction that was not statistically significant (P for trend = 0.42). Overall, the results for vitamin B12 tended to mimic those for folate, whereas the associations for homocysteine tended to be in the opposite direction. None of the results of this study were statistically significant, but patterns of the associations are in accord with hypothesized mechanistic pathways concerning B vitamins and cervical cancer.

Detection of Chlamydia trachomatis DNA in archival paraffinized specimens from chronic salpingitis cases using the polymerase chain reaction.

OBJECTIVE: To identify Chlamydia trachomatis by the polymerase chain reaction (PCR) in fallopian tube tissues with chronic salpingitis. DESIGN: Retrospective case-control study. SETTING: Academic tertiary institution. PATIENT(S): Women with a pathological diagnosis of chronic salpingitis or normal fallopian tube hospitalized between September 1992 and November 1994. Initial identification of 248 specimens with final analysis of 154. INTERVENTION(S): Paraffin-embedded fallopian tube tissues were analyzed with use of PCR to detect C. trachomatis. MAIN OUTCOME MEASURE(S): Identification of C. trachomatis DNA; demographics of age, ethnicity, parity, history of sexually transmitted disease, and surgical procedure. RESULT(S): C. trachomatis DNA was detected in 9 of 77 chronic salpingitis cases. Seventy-seven controls were negative for C. trachomatis. No statistically significant difference in age or ethnicity between cases and controls was identified. Nulliparity was more frequent in cases (26 of 74) than controls (14 of 76). Sexually transmitted disease history was more prevalent in cases (24 of 74) than controls (6 of 76). Chlamydia infection was not associated with a particular surgical indication. CONCLUSION(S): Chronic salpingitis is highly associated with the presence of C. trachomatis infection as detected by PCR.

Population genetics of the porB gene of Neisseria gonorrhoeae: different dynamics in different homology groups.

The porB locus codes for the major outer membrane protein of Neisseria gonorrhoeae. Alleles of this locus have been assigned to two homology groups based on close sequence and immunological relationships and are designated as either PIA or PIB. Several population parameters were estimated and compared among these two groups using a data set of 22 PIA sequences and 91 PIB sequences obtained from diverse geographic localities and from time periods spanning approximately 50 years. Recombination appears to be extensive in the porB gene. While the recombination rates are similar for the PIA and PIB sequences, the relative contribution of recombination to genetic diversity is higher for the PIA sequences. Alleles belonging to the PIB group show greater genetic diversity than do those in the PIA group. Although phylogenetic analysis did not reveal temporal or geographic clustering of sequences, estimates of gene flow and the fixation index suggested that PIB sequences exhibit population substructure based on geographic locality. Selection acts in these homology groups in a different way. While positive Darwinian selection is the dominant force driving the evolution of the PIA sequences, purifying selection operates also on the PIB sequences. These differences may be attributable to the greater propensity of PIA strains, as compared with PIB strains, to cause disseminated gonococcal infection, which would expose the former to intense selection pressure from the host immune system. The molecular evolution of Neisseria gonorrhoeae seems to be driven by the simultaneous action of selection and recombination, but under different rates and selection pressures for the PIA and PIB homology groups.

Serum antibodies to human papillomavirus 16 proteins in women from Brazil with invasive cervical carcinoma.

Serum samples from 194 cases and 217 controls participating in a case-control study of invasive cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 virus-like particles (VLPs) by ELISA. The prevalence of antibody in cases and controls was 47.4 versus 24.4% (P < 0.001). The prevalence was higher in women who had HPV-16 DNA in the genital tract (54.2%) than in those with other HPVs (36.8%) or no HPVs (44.8%), but the differences were not statistically significant. Among cases and controls, HPV-16 VLP antibodies were associated with a greater number of lifetime sexual partners (chi2 for trend, P < 0.001). Among controls, age was inversely associated with HPV-16 VLP seroreactivity (chi2 for trend, P = 0.019). The sera were previously tested for antibodies to HPV-16 E6 and E7 oncoproteins; there was no correlation between antibody titers to HPV-16 E6 or E7 and VLPs. The HPV-16 serological assays were compared as screening tests for invasive cervical cancer. The sensitivity and specificity estimates were 47.4 and 75.6% for HPV-16 VLP serology, 63.4 and 89.9% for either HPV-16 E6 or E7 serology, and 53.6 and 93.6% for high titers of either HPV-16 E6 or E7 or VLP antibodies. The utility of HPV-16 VLP ELISA as a screening test for invasive cervical cancer is limited by a high seroprevalence in women with probable prior exposure to HVP 16 but without disease.

Adeno-associated virus and development of cervical neoplasia

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) - control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.(Au)

Adeno-associated virus and development of cervical neoplasia.

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.

Emerging HIV infections with distinct subtypes of HIV-1 infection among injection drug users from geographically separate locations in Guangxi Province, China.

Heroin users from Guangxi province, a southern province of China that borders Vietnam in the south and Yunnan province in China in the west, were studied for prevalence and risk factors for HIV-1 infection. Viral env sequences from HIV-1-positive individuals were also determined for subtypes of HIV-1. The overall HIV prevalence among 227 heroin users was 40%. Most had used drugs for < or = 3 years. Sharing of injection equipment and unprotected sex were significantly associated with HIV-1 infection. Subtypes C and E HIV-1 were detected in infected heroin users and were sharply segregated in two geographic locations: only subtype C was found in a border city with Yunnan province, whereas only subtype E was found in a city bordering northern Vietnam. HIV-1 strains within each subtype were remarkably homogenous, with a mean intersubject DNA distance of 2.32% for subtype E and 1.13% for subtype C, respectively. Phylogenetic analysis of C2-V5 region of Guangxi subtype E env sequences revealed significant clustering with subtype E sequences from southern Vietnam and Cambodia. These results suggest that HIV-1 infection among heroin users in Guangxi represents two emerging epidemics initiated from distinct sources: one from Vietnam and another from Yunnan province. Factors associated with HIV-1 infection were not restricted to injection practices. Unprotected sexual behaviors are likely to increase the probability of HIV transmission beyond this high-risk population. Designing and implementing effective intervention strategies targeted toward both injection drug use and high risk sexual behavior are urgently needed to further reduce HIV-1 spread in China.

A survey of human papillomavirus 16 antibodies in patients with epithelial cancers.

Human papillomavirus (HPV), particularly HPV 16, is linked to the development of cervical cancer. However, the role of HPV 16 in a number of extra-cervical epithelial tumours is controversial. To assess exposure to HPV 16 in patients with different cancers, we conducted a large serosurvey of 905 patients with 21 types of tumours and measured IgG to HPV 16 virus-like particles (VLPs) using a well characterized enzyme linked immunosorbent assay (ELISA). Patients with cervical cancer were considered 'positive controls', as about half were expected to be specifically HPV 16-related. A non-cancer study group consisting of 48 patients with endocrine disorders (eg diabetes) was also tested. HPV 16 antibody prevalence was highest in patients with cancers of the cervix (52% +/- 7%), vulva (27% +/- 9%), vagina (27% +/- 13%) and penis (63% +/- 16%). Seroprevalence was much lower in the non-cancer group (4% +/- 3%) and all other cancer patients: uterus (9% +/- 4%); ovary (4% +/- 3%); testis (5% +/- 4%); prostate (6% +/- 4%); squamous carcinoma (6% +/- 3%) and adenocarcinoma (4% +/- 3%) of the lung; rectum (2% +/- 2%); pancreas (8% +/- 4%); colon (2% +/- 2%); stomach (0%); oesophagus (8% +/- 4%); buccal cavity (12% +/- 5%); breast (10% +/- 4%); non-melanomatous (9% +/- 6%) and melanomatous (6% +/- 3%) skin tumours; bladder (8% +/- 4%); and kidney (2% +/- 2%). The results confirm the strong relation of HPV with several lower anogenital tract tumours, but, at least in this population, fail to identify additional epithelial tumours associated with high seroprevalence of HPV 16 VLP antibodies.

Mapping of specific and promiscuous HLA-DR-restricted T-cell epitopes on the Plasmodium falciparum 27-kilodalton sexual stage-specific antigen.

We have characterized HLA-DR-restricted T-cell epitopes on the 27-kDa protein (Pfg27), a sexual stage-specific antigen, of the human malaria parasite Plasmodium falciparum in subjects with a history of malaria. Pfg27, expressed early in the sexual stages, is recognized by monoclonal antibodies capable of reducing the infectivity of gametocytes in mosquitoes. By using 16 Pfg27-specific CD4(+)-T-cell clones derived from three donors, seven different T-cell epitopes were identified. Among them, P11 (amino acids 191 to 210 of the Pfg27 sequence, IDVVDSYIIKPIPALPVTPD) was found to contain a previously described binding motif for multiple HLA-DR allotypes. Indeed, P11 was found to be promiscuous in that it could be recognized by T cells in the context of at least five different HLA-DR molecules. The cytokine profile of the clones was mixed. Seven of nine T-cell clones exhibited a Th0-like cytokine profile, producing high levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) upon stimulation with specific peptides and mitogens. The other two clones had a Th1-like cytokine profile with high expression of IFN-gamma and no IL-4. Identification of a promiscuous epitope in Pfg27 could play a significant role in the design of a subunit vaccine for suppressing malaria transmission.

A multifaceted study of human papillomavirus and prostate carcinoma.

BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.