JC polyoma viruria associates with protection from chronic kidney disease independently from apolipoprotein L1 genotype in African Americans.

Background: Viral infections can trigger chronic kidney disease (CKD) and the urine virome may inform risk. The Natural History of APOL1-Associated Nephropathy Study (NHAANS) reported that urine JC polyomavirus (JCPyV) associated with a lower risk of APOL1-associated nephropathy in African Americans. Herein, association was assessed between urine JCPyV with CKD in African Americans independent from the APOL1 genotype. Methods: Quantitative polymerase chain reaction was performed for urinary detection of JCPyV and BK polyoma virus (BKPyV) in 200 newly recruited nondiabetic African Americans. A combined analysis was performed in these individuals plus 300 NHAANS participants. Results: In the 200 new participants, urine JCPyV was present in 8.8% of CKD cases and 45.8% of nonnephropathy controls (P = 3.0 × 10-8). In those with APOL1 renal-risk genotypes, JCPyV was detected in 5.1% of cases and 40.0% of controls (P = 0.0002). In those lacking APOL1 renal-risk genotypes, JCPyV was detected in 12.2% of cases and 48.8% of controls (P = 8.5 × 10-5). BKPyV was detected in 1.3% of cases and 0.8% of controls (P = 0.77). In a combined analysis with 300 NHAANS participants (n = 500), individuals with urine JCPyV had a 63% lower risk of CKD compared with those without urine JCPyV (odds ratio 0.37; P = 4.6 × 10-6). RNA fluorescence in situ hybridization confirmed the presence of JCPyV genomic DNA and JCPyV messenger RNA (mRNA) in nondiseased kidney. Conclusions: Inverse relationships exist between JCPyV viruria and non-diabetic CKD. Future studies should determine whether renal inflammation associated with CKD is less permissive for JCPyV reactivation/replication or whether JCPyV is a marker of reduced host immune responsiveness that diminishes immune pathologic contributions to CKD.

Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma.

Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes.

[Incidence of skin and non-skin cancers in Afro-Caribbean renal transplant recipients: Guadeloupe data from 2004 to 2011]. / Incidence des cancers cutanés et non cutanés chez les transplantés rénaux afro-caribéens : données guadeloupéennes de 2004 à 2011.

BACKGROUND: Cancer is the main complication of transplantation surgery. The literature concerning renal transplant recipients among the Afro-Caribbean population is scant. The aim of this study was to determine the incidence of cancer in these patients, with the secondary objective being to identify predisposing factors for cancer. PATIENTS AND METHODS: This was an epidemiological and retrospective study that included all Guadeloupians of phototype V-VI undergoing renal transplantation from 01/01/2004 to 31/12/2011. Skin cancer screening was performed before transplantation and during an annual dermatological consultation following transplantation. Screening for non-cutaneous cancers was guided by clinical symptoms or by the results of the screening examinations recommended in the current guidelines. At the study time-point (31/12/2011), all patients were examined by a dermatologist. RESULTS: One hundred and two patients were included : 42 women and 60 men (mean age: 52.1±11.6 years at transplantation). Eight cancers were diagnosed. The cumulative incidence of cancer was 7.8% at 3 years. Three factors were associated with more rapid onset of cancer: personal history or familial history of cancer, and genital lesion induced by HPV. CONCLUSION: Our results suggest a low incidence of cancer in Afro-Caribbean renal transplant patients. Personal or family history of cancer and HPV-induced genital lesions would appear to accelerate the onset of cancer in this population.

Association of interferon gamma gene polymorphisms with BK virus infection among Hispanic renal allograft recipients.

BACKGROUND: BK virus nephropathy is one of the most common viral infections that affect up to 10% of renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Interferon-gamma (IFN-γ) gene polymorphisms have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection, cytomegalovirus viremia, and disease. IFN-γ is known to have potent inhibitory effects on BK virus gene expression, both at the level of transcription and translation. METHODS: It was investigated whether IFN-γ polymorphisms are associated with BKV infection. Genotyping of four single-nucleotide polymorphisms located in the IFN-γ gene were performed on DNA collected from a total of 251 RTRs (71 RTRs with BKV infection and 180 without BKV infection). RESULTS: Analysis of the results showed that IFN-γ (rs12369470) CC genotype was significantly associated with susceptibility to BKV infection (OR: 2.9, 95% CI: 1.29-6.44, P=0.007) while the IFN-γ +874 (rs2435061) TT and (rs2406918) CC genotypes appear to be markers for protection against BKV infection (OR: 0.29, 95% CI: 0.1-0.83, P=0.01 for rs245061; OR: 0.61, 95% CI: 0.4-0.94, P=0.02 for rs24069718). A haplotype analysis using the combination of rs2435061-rs2406918-rs2870953 showed that the A-G-T haplotype was associated with a significantly reduced risk for BKV infection (OR: 0.43, 95% CI: 0.25-0.73, P=0.001). CONCLUSION: Polymorphisms in the IFN-γ gene may confer certain protection or predisposition for BKV infection.

JC polyoma virus interacts with APOL1 in African Americans with nondiabetic nephropathy.

Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

The prevalence of Merkel cell polyomavirus in Japanese patients with Merkel cell carcinoma.

BACKGROUND: A novel polyomavirus, the Merkel cell polyomavirus (MCPyV) has been implicated in the pathogenesis of Merkel cell carcinoma (MCC); however, the prevalence of MCPyV in Japan has not been extensively investigated. OBJECTIVE: To clarify the prevalence of MCPyV in Japanese patients with MCC. METHODS: MCPyV DNA was examined by polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded (FFPE) or frozen tissue samples from 26 patients with MCC diagnosed in four medical centers in Japan. Immunohistochemistry was simultaneously performed using a monoclonal antibody against the viral large T (LT) antigen. FFPE samples from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were also analyzed as controls. RESULTS: Twenty-three out of 26 cases (88.5%) were positive for MCPyV DNA by PCR. The amplified products harbored 4 patterns of mutations. Phylogenetic analysis demonstrated that one of our strains was closely related to the other Japanese strains previously reported. The LT antigen was expressed in various degrees in 20 of 26 cases (76.9%) by immunohistochemistry. Histological type had little relation to CM2B4 positivity, whereas 3 of 5 trabecular-type tumors showed no staining. The immunoreactivity for CM2B4 did not correlate with the relative viral DNA load. In BCC and SCC, the LT antigen was immunohistochemically positive, but MCPyV DNA was not detected by PCR. The cells around some MCC and non-MCC tumors were stained with CM2B4 with a distribution similar to CD20- and CD45RO- (especially CD8-) positive lymphocytes. CONCLUSION: MCPyV was highly positive in Japanese patients with MCC. It is of note that the positive rate differs depending upon the detection method.

P53 and PCNA is positively correlated with HPV infection in laryngeal epitheliopapillomatous lesions in patiets with different ethnic backgrounds in Xinjiang.

OBJECTIVE: To explore the correlation of human papillomavious (HPV) infection with expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. METHODS: 166 biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20 laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerase chain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed using immunohistostaining. RESULTS: The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3%) than in LP (6.3%) (P<0.0005). Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV 16/18 coinfection than those of Uygur and Kazak ethnicity (P<0.05). Overexpression of p53 and PCNA were higher in LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P<0.005, and P<0.005, respectively). That of p53 was not associated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated with clinical stage. CONCLUSIONS: These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC and LP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpression of p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation in HPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.

[Cancer incidence in Italian natives and in first-generation immigrants to Italy]. / L'incidenza dei tumori in cittadini nati in Italia e in immigrati di prima generazione.

OBJECTIVE: The aim of this study was to evaluate differences in cancer incidence in populations born in different countries in the area covered by the Tuscan Cancer Registry. SETTING: We selected cancer cases diagnosed during the period 1998-2005 in the population resident in the provinces of Firenze and Prato. Each case was classified according to the place of birth: a) born in Italy, b) born in countries with high migration (PFPM), born in other highly developed countries (PSA).To compute incidence rates we used as denominator the health regional registry. MAIN OUTCOME MEASURES: We used the European standard population in computing standardized incidence rates (restricted to the age group 20-59 years) and the standardized rate ratio (SRR) in order to compare subjects born in different countries. RESULTS: During the period 1998-2005, 14 791 invasive cancers were diagnosed (non-melanoma skin excluded) in subjects aged 20-59 years old, 4.2% in subjects born in countries outside Italy (1.2% in other PSA e 3.0% in PFPM). Incidence in subjects born in PSA did not differ significantly from incidence in subjects born in Italy. Incidence rates among subjects born in PFPM were statistically lower, both in men (151.2 per 100 000) and women (199.3 per 100 000), than in subjects born in Italy (243.5 men e 337.5 women). On the contrary, liver and cervix uteri cancer incidence showed higher rates among subjects born in PFPM (liver: SRR=2.13, p=0.007; cervix uteri: SRR=1.88, p=0.0095). CONCLUSION: Subjects born in countries with high migration showed a level of incidence lower than subjects born in Italy (healthy migration effect). Incidence was higher among subjects born in PFPM only for liver and cervix uteri, cancers with a virological aetiology. The migration phenomena open new study prospectives, but also methodological questions (definition of immigrants and of reference populations).

Prevalence of high-risk HPV types and abnormal cervical cytology in American Indian/Alaska Native women, 2003-2005.

UNLABELLED: OBJECTIVES; We described prevalence estimates of high-risk human papillomavirus (HR-HPV), HPV types 16 and 18, and abnormal Papanicolaou (Pap) smear tests among American Indian/Alaska Native (AI/AN) women compared with women of other races/ethnicities. METHODS: A total of 9,706 women presenting for cervical screening in a sentinel network of 26 clinics (sexually transmitted disease, family planning, and primary care) received Pap smears and HR-HPV type-specific testing. We compared characteristics of 291 women self-identified as AI/AN with other racial/ethnic minority groups. RESULTS: In our population, AI/AN and non-Hispanic white (NHW) women had similar age- and clinic-adjusted prevalences of HR-HPV (29.1%, 95% confidence interval [CI] 23.9, 34.3 for AI/AN women vs. 25.8%, 95% CI 24.4, 27.2 for NHW women), HPV 16 and 18 (6.7%, 95% CI 3.9, 9.6 for AI/AN women vs. 8.8%, 95% CI 7.9, 9.7 for NHW women), and abnormal Pap smear test results (16%, 95% CI 11.7, 20.3 for AI/AN women vs. 14.9%, 95% CI 13.7, 16.0 for NHW women). AI/AN women had a higher prevalence of HR-HPV than Hispanic women, and a similar prevalence of HPV 16 and 18 as compared with Hispanic and African American women. CONCLUSIONS: We could not demonstrate differences in the prevalence of HR-HPV, HPV 16 and 18, or abnormal Pap smear test results between AI/AN and NHW women. This finding should improve confidence in the benefit of HPV vaccine and Pap smear screening in the AI/AN population as an effective strategy to reduce rates of cervical cancer.

Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia.

PURPOSE: The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population. METHODS: We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction. RESULTS: HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P < 0.001, OR = 4.3 after adjustment for habits) when compared to controls. High-risk HPV was found to be significantly associated with OSCC cases (P < 0.05). Demographic profiles of age, gender, race and habits were not associated with HPV presence in cases and controls. However, significantly less HPV positivity was seen in poorly differentiated compared to well-differentiated OSCCs. No significant association was found between HPV positivity and p53 polymorphisms in cases and control groups. Additionally, we found no association of codon 72 polymorphism with oral cancer. CONCLUSIONS: This study indicates that high-risk HPV infection is one of the contributing factors for OSCCs. HPV 16 was the predominant type found in Malaysian patients with OSCC. Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.

Low prevalence of BK virus nephropathy on nonprotocol renal biopsies in Iranian kidney transplant recipients: one center's experience and review of the literature.

OBJECTIVES: BK virus-associated nephropathy in renal transplant recipients has been increasing in frequency in recent years. This rise is probably because of widespread use of highly potent immunosuppressive regimens, and increased immunosuppression load leads to inability of the recipients to increase a successful antiviral immune response. The incidence of BK virus-associated nephropathy in different reports is between 1% and 10%, with an allograft loss in significant numbers of patients, especially when timely diagnosis and treatment is not restored. We report our experience on BK virus nephropathy in our institute. MATERIALS AND METHODS: All renal transplant biopsies performed at our center between 2001 and 2006 were immunohistochemically screened for the presence of PV-specific protein (SV40 Ag). The histologic diagnosis of BK virus-associated nephropathy was made upon the observation of morphologic changes in tubular epithelium and confirmation with immunohistochemical staining. We reviewed the clinical records of the subjects for demographic, clinical, and laboratory data. RESULTS: BK virus nephropathy was found in 0.93% of all investigated allograft biopsies (1/108) and in 1.04% of all recipients (1/96; mean age of recipients, 36.48±14.10 years; age range, 13-74 years); 54 of them were male (57%). Type of kidney transplant was living-unrelated donor 76 (79%), living-related donor 13 (14%), and deceased donor 7. Seventeen patients (18%) were transplanted for a second time. Immunosuppressive drugs in 87 of recipients (90%) were cyclosporine, mycophenolate mofetil, and prednisolone. Our patient who developed BK virus-associated nephropathy 9 months after transplant was a 37-year-old man on prednisone, cyclosporine, and azathioprine immunosuppresion. He lost his graft 4 months after diagnosis. CONCLUSIONS: Although BK virus nephropathy after renal transplant is uncommon, it is a serious complication causing loss of the allograft. It should be included in the clinical differential diagnosis of transplant dysfunction.

Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population.

UNLABELLED: BK virus nephropathy (BKVN) is an increasingly recognized cause of kidney allograft loss and is thought to be related to the newer, more potent immunosuppressive agents. Conflicting information has been reported on risk factors for BK infection. PURPOSE: To determine incidence, associated factors, and outcome of BKVN in our kidney transplant population in order to improve identification and management. METHODS: Kidney transplants from January 2000 to December 2005 were retrospectively reviewed. Data were collected for patients with biopsy-proven BKVN including age, sex, body mass index (BMI), etiology of renal failure, other medical diseases, donor type, surgical complications, rejection and infection, time to diagnosis, induction, immunosuppressive and antiviral therapy, and clinical outcome. A control group of patients matched for sex, age, type of graft, etiology of kidney disease, and BMI, was established for comparison. STUDY GROUP: During this period, 20 (4%) of 497 transplanted patients were diagnosed with BKVN. Thirteen (65%) were males, 8 (40%) were young adults (ages 21-40), and 18 (90%) received grafts from cadaveric donors (P=0.05). Twelve (60%) had hypertensive renal disease, 2 (10%) also had diabetes, and 16 (80%) had a BMI >25 (P=0.01). Lymphoceles occurred in 5 patients (25%). Mean creatinine level at diagnosis was 2.7 mg/dL and mean time to diagnosis was 23 months. Ten patients (50%) had leukopenia at or within a year before biopsy (P=0.001). Viruses other than BK occurred in 9 patients: varicella zoster virus in 3, cytomegalovirus in 2, herpes simplex virus in 1, molluscum contagiosum in 1, Epstein-Barr virus in 1, and human papillomavirus in 1. Eighteen patients (90%) had related rejection (P= 0.001) and 4 (20%) suffered allograft loss (P= 0.001). Basiliximab (living donors) and anti-thymocyte globulin (cadaver donors) were given for induction. All patients were on triple therapy; 15 on prednisone and sirolimus, with either tacrolimus in 8, cyclosporine in 4, mycophenolate in 1, or mycophenolate and tacrolimus in 2. The other 5 received prednisone with tacrolimus and mycophenolate. Graft loss occurred in 2 patients on tacrolimus and mycophenolate, 1 patient on tacrolimus and sirolimus, and 1 patient on cyclosporine and sirolimus. Immunosuppression was decreased in all patients. Two were given cidofovir for 6 months and had stable creatinine levels at the end of the study. Records were reviewed until April 2007. There were no deaths in this cohort. CONTROL GROUP: The number of rejections experienced by patients with BKV was much higher (P<0.0001), but the rate of graft loss was similar between the 2 groups (P=0.19). Viral co-infection was more frequent in patients with BKV (P=0.04). No episodes of leukopenia were reported for any of the patients in the control group (P=0.001). Immunosuppression with tacrolimus and sirolimus was more frequent in the BKV group, but this was not statistically significant (P=0.18, 0.28, respectively). The number of lymphoceles was larger in patients with BKV, but the difference was not statistically significant (P=0.35). CONCLUSION: BKVN is present in our transplant population and results in a high rate of allograft rejection with varying rates of graft loss. Associated factors were deceased donor and immunosuppression with potent agents, particularly tacrolimus and sirolimus. We also found a higher frequency of obesity, viral co-infection, and leukopenia. Routine screening and timely biopsy could prove cost-effective and significantly reduce morbidity.

Prevalence of BK virus subtype I in Germany.

The primary infection with human polyomavirus BK (BKV) occurs in early childhood and leads to viral latency within the urogenital tract. Up to 90% of the adult population are seropositive. In immunosuppressed patients, the BKV may be reactivated resulting in typical disease patterns like hemorrhagic cystitis and tubulointerstitial nephritis. Based on serological and molecular methods, BKV isolates were classified into four subtypes previously. Sixty specimens obtained from German renal and bone marrow transplant recipients were analyzed to gain data on the prevalence of BKV subtypes in Germany. With 90.9%, BKV subtype I was found to be predominant in both patient groups. 6.1% of BKV strains were classified as subtype IV. This pattern of phylogenetic distribution is similar to that demonstrated previously in England, Tanzania, the United States and Japan. Remarkably, there was one German BKV virus with a sequence which clusters together with strain SB in subtype II. The BKV subtype I was found to consist of at least three subgroups designated as Ia, Ib, and Ic. While the majority of the German sequences represent subgroup Ic, most of the Japanese sequences are clearly distinct. These findings support the hypothesis of distinct geographical prevalence of BKV subgroups. For the genotyping region, a relationship of BKV subgroups to disease patterns like hemorrhagic cystitis or tubulointerstitial nephritis could not be demonstrated.

Identification of a genomic subgroup of BK polyomavirus spread in European populations.

BK polyomavirus (BKV) is highly prevalent in the human population, infecting children without obvious symptoms and persisting in the kidney in a latent state. In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates worldwide are classified into four serologically distinct subtypes, I-IV, with subtype I being the most frequently detected. Furthermore, subtype I is subdivided into subgroups based on genomic variations. In this study, the distribution patterns of the subtypes and subgroups of BKV were compared among four patient populations with various immunosuppressive states and of various ethnic backgrounds: (A) Finnish renal-transplant recipients; (B) Irish/English haematopoietic stem-cell transplant recipients with and without haemorrhagic cystitis; (C) Japanese renal-transplant recipients; and (D) Japanese bone-marrow transplant recipients. The typing sequences (287 bp) of BKV in population A were determined in this study; those in populations B-D have been reported previously. These sequences were subjected to phylogenetic and single nucleotide polymorphism analyses. Based on the results of these analyses, the BKV isolates in the four patient populations were classified into subtypes and subgroups. The incidence of subtype IV varied significantly among patient populations. Furthermore, the incidence of subgroup Ib-2 within subtype I was high in populations A and B, whereas that of Ic was high in populations C and D (P<0.01). These results suggest that subgroup Ib-2 is widespread among Europeans, whereas Ic is unique to north-east Asians. Furthermore, a phylogenetic analysis based on complete BKV DNA sequences supported the hypothesis that there is geographical separation of European and Asian BKV strains.

Polyomavirus SV40 infections in Kazakhstan.

OBJECTIVES: To examine the prevalence of polyomavirus SV40 infections in Kazakhstan, a central Asian country known to have used potentially contaminated SV40 poliovaccines before 1962. METHODS: Cross-sectional study of 307 healthy volunteers from two ethnic groups (Kazakhs and Russians) in Almaty, Kazakhstan, from May through August 1999 using a specific SV40 plaque-reduction neutralization assay. RESULTS: Of the 307 volunteers enrolled in the study, 154 were Kazakhs and 153 were Russians. The overall prevalence of SV40 antibodies was 4.9%, and there was no significant difference between the ethnic groups (p = 0.7) or between males and females. The median SV40 neutralizing antibody titers in Kazakhs and Russians were 1:40 (range 1:10-1:500) and 1:20 (range 1:10-1:500), respectively. The median ages of SV40-infected Kazakhs and Russians were not different (42 vs. 24 years; p = 0.1), although there was a trend for increased seropositivity among older Kazakhs. There was no difference in SV40 positivity between those whose childhoods were spent in rural or in urban areas (p = 0.4). Importantly, 60% (9/15) of the subjects seropositive for SV40 were born from 1969 to 1980s, when poliovaccines were free from SV40. CONCLUSIONS: This study showed evidence of polyomavirus SV40 infections in Kazakhstan, not only among individuals potentially exposed to contaminated poliovaccines, but in younger people not exposed to such vaccines. As increasing evidence indicates an association of SV40 with selected types of human malignancies, prospective studies are needed to examine the risk of SV40 infection with the development of neoplasias.

Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk.

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months (n =442). Highly significant differences were observed between ethnic groups (P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.

Active and passive smoking, high-risk human papillomaviruses and cervical neoplasia.

Few studies have evaluated the role of passive smoke exposure and cervical neoplasia risk. We assessed the role of active and passive cigarette smoke exposure and risk of cervical squamous intraepithelial lesion (SIL) in a case-control study based in a South Carolina Health Department; 59 high-grade SIL (HSIL) cases, 313 low-grade SIL (LSIL) cases and 427 controls were recruited and interviewed. Passive cigarette smoke exposure was significantly (P < 0.05) associated with high grade SIL (adjusted odds ratio (aOR) = 2.2) and low-grade SIL (aOR = 1.4). Active smoking was associated with SIL only among White women (aOR = 1.8). High-risk human papillomaviruses (HR-HPVs) appear to interact with active cigarette smoking to increase HSIL risk. HSIL cases compared with LSIL cases were significantly more likely to be HR-HPV positive current smokers (aOR = 3.0; 95% CI: (1.2, 7.7)). These data suggest that active and perhaps passive smoke exposure may be important co-factors in HSIL development among HR-HPV positive women.

Risk factors for cervical intraepithelial neoplasia in southwestern American Indian women.

The authors assessed risk factors for cervical intraepithelial neoplasia (CIN) among southwestern American Indian women using case-control methods. Cases were New Mexico American Indian women with biopsy-proven grade I (n = 190), grade II (n = 70), or grade III (n = 42) cervical lesions diagnosed between November 1994 and October 1997. Controls were American Indian women from the same Indian Health Service clinics with normal cervical epithelium (n = 326). All subjects underwent interviews and laboratory evaluations. Interviews focused on history of sexually transmitted diseases, sexual behavior, and cigarette smoking. Laboratory assays included polymerase chain reaction-based tests for cervical human papillomavirus infection, tests for gonorrhea and chlamydia, wet mounts, and serologic assays for antibodies to Treponema pallidum, herpes simplex virus, and hepatitis B and C viruses. In multiple logistic regression analysis, the strongest risk factors for CIN II/III among American Indian women were human papillomavirus type 16 infection (adjusted odds ratio (OR) = 7.6; 95% confidence interval (CI): 2.4, 23.2), any human papillomavirus infection (OR = 5.8; 95% CI: 3.3, 10.0), low income (OR = 3.3; 95% CI: 1.7, 6.2), and history of any sexually transmitted disease (OR = 2.0; 95% CI: 1.1, 3.5). Unlike previous research, this study found no strong associations between CIN and sexual activity or cigarette smoking.

Human papillomavirus type 33 DNA in breast cancer in Chinese.

BACKGROUND: The association between human papillomavirus (HPV) and anogenital tumors, especially cervical cancer, is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer. METHODS: We used PCR and Southern blot hybridization to analyze HPV-related DNA specimens from 32 cases of invasive ductal carcinoma operated upon in the Shanghai region of China. RESULTS: DNA derived from HPV33 was detected in 14 cases (43.8%). No HPV16 or HPV18 DNA was detected in any of the cases in this study. This is the first report demonstrating a correlation between HPV33 infection and breast cancer. CONCLUSIONS: Our results suggest that HPV33 infection may be involved in the pathogenesis of breast cancer in Chinese.