Thirty-five year mortality following receipt of SV40- contaminated polio vaccine during the neonatal period

Early poliovirus vaccines, both inactivated and live attenuated, were inadvertently contaminated with simian virus 40 (SV40), a monkey virus known to be oncogenic for newborn hamsters. Although large epidemiologic studies have not identified an elevated cancer risk in persons who received SV40-contaminated vaccines, fragments of SV40 DNA have recently been identified in certain human tumours. We report the follow-up of a cohort of 1073 persons, unique because they received SV40-contaminated poliovirus vaccines as newborns in 1961–63. A previous report of the status of these subjects as of 1977–79 identified 15 deaths, none due to cancer. The present study utilized the National Death Index to identify deaths in the cohort for the years 1979–96. Expected deaths were calculated from Cleveland area sex-, age-, race- and year-specific mortality rates. Increased mortality from all causes was not found. 4 deaths from cancer were found compared to 3.16 expected (P= 0.77). However, 2 deaths from testicular cancer occurred, compared to 0.05 expected (P= 0.002), which may be a chance finding due to multiple comparisons. There were 2 deaths due to leukaemia, a non-significant finding, and no deaths due to tumours of the types putatively associated with SV40. Although these results are, for the most part, consistent with other negative epidemiologic investigations of risks from SV40-contaminated vaccines, further study of testicular cancer may be warranted, and it will be important to continue monitoring this cohort which is now reaching middle-age. © 2001 Cancer Research Campaig

HIV Serostatus and Tumor Differentiation Among Patients with Cervical Cancer at Bugando Medical Centre.

Evidence for the association between Human immunodeficiency virus infection and cervical cancer has been contrasting, with some studies reporting increased risk of cervical cancer among HIV positive women while others report no association. Similar evidence from Tanzania is scarce as HIV seroprevalence among cervical cancer patients has not been rigorously evaluated. The purpose of this study was to determine the association between HIV and tumor differentiation among patients with cervical cancer at Bugando Medical Centre and Teaching Hospital in Mwanza, North-Western Tanzania. This was a descriptive analytical study involving suspected cervical cancer patients seen at the gynaecology outpatient clinic and in the gynaecological ward from November 2010 to March 2011. A total of 91 suspected cervical cancer patients were seen during the study period and 74 patients were histologically confirmed with cervical cancer. The mean age of those confirmed of cervical cancer was 50.5 ± 12.5 years. Most patients (39 of the total 74-52.7%) were in early disease stages (stages IA-IIA). HIV infection was diagnosed in 22 (29.7%) patients. On average, HIV positive women with early cervical cancer disease had significantly more CD4+ cells than those with advanced disease (385.8 ± 170.4 95% CI 354.8-516.7 and 266.2 ± 87.5, 95% CI 213.3-319.0 respectively p = 0.042). In a binary logistic regression model, factors associated with HIV seropositivity were ever use of hormonal contraception (OR 5.79 95% CI 1.99-16.83 p = 0.001), aged over 50 years (OR 0.09 95% CI 0.02-0.36 p = 0.001), previous history of STI (OR 3.43 95% CI 1.10-10.80 p = 0.035) and multiple sexual partners OR 5.56 95% CI 1.18-26.25 p = 0.030). Of these factors, only ever use of hormonal contraception was associated with tumor cell differentiation (OR 0.16 95% CI 0.06-0.49 p = 0.001). HIV seropositivity was weakly associated with tumor cell differentiation in an unadjusted analysis (OR 0.21 95% CI 0.04-1.02 p = 0.053), but strong evidence for the association was found after adjusting for ever use of hormonal contraception with approximately six times more likelihood of HIV infection among women with poorly differentiated tumor cells compared to those with moderately and well differentiated cells (OR 5.62 95% CI 1.76-17.94 p = 0.004).\ud Results from this study setting suggest that HIV is common among cervical cancer patients and that HIV seropositivity may be associated with poor tumour differentiation. Larger studies in this and similar settings with high HIV prevalence and high burden of cervical cancer are required to document this relationship

The prevalence of cervical cytology abnormalities and human papillomavirus in women infected with the human immunodeficiency virus

<p>Abstract</p> <p>Introduction</p> <p>The human papillomavirus (HPV) is the major etiologic agent in the development of cervical cancer and its natural history of infection is altered in persons infected with the human immunodeficiency virus (HIV). The prevalence of HPV infection and cervical dysplasia in the HIV sero-positive females in the Bahamas is not known. Finding out the prevalence would allow for the establishment of protocols to optimize total care of this population and help prevent morbidity and mortality related to cervical cancer.</p> <p>Objective</p> <p>The Objective of this study is to determine the prevalence of high risk HPV genotypes and the prevalence of cervical dysplasia in the HIV sero-positive females attending the Infectious Disease Clinic at the Princess Margaret Hospital, Nassau, Bahamas.</p> <p>Methods</p> <p>One hundred consecutive, consenting, non-pregnant, HIV-sero-positive females from the Infectious Disease Clinic at the Princess Margaret Hospital in Nassau, Bahamas were screened for high-risk HPV infections and cervical cytology abnormalities using liquid-based pap smear and signal amplification nucleic acid method for HPV detection. A questionnaire was also utilized to gather demographic information and obtain information on known risk factors associated with HPV infections such numbers of partners.</p> <p>Results</p> <p>The prevalence of high-risk HPV was 67% and cervical abnormalities were noted in 44% of the study population. High-risk HPV types were more likely to be present in women with CD4+ cell counts less than 400 μl^-1and in women with cervical cytology abnormalities (97%). The most common cervical abnormality was low-grade squamous intraepithelial lesions.</p> <p>Conclusion</p> <p>Findings suggest that HIV-sero positive females should have HPV testing done as part of their normal gynecology evaluation and these patients should be encouraged and provisions be made for ease of access having regular PAP smears and HPV testing.</p

A cautionary tale of virus and disease

The recent identification of the gammaretrovirus XMRV and a second gammaretrovirus of a different subtype in chronic fatigue syndrome has aroused much interest, not least among sufferers. However, it remains highly controversial whether the detection of these viruses represents true infection or laboratory artifacts

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm(3), CI = 0.40-0.97).In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women

The burden, distribution and risk factors for cervical oncogenic human papilloma virus infection in HIV positive Nigerian women

Background: The expected reduction in cervical cancer incidence as a result of increased access to antiretroviral therapy is yet to be seen. In this study we investigated the effect of HIV infection and treatment on high-risk (hr) human papilloma virus (HPV) prevalence and distribution. Methods: Cervical cells from 515 (220 HIV positive and 295 HIV negative) women, recruited during community cervical cancer screening programme in states of Ogun and Lagos and at the cervical cancer screen clinic, Nigerian Institute of Medical Research Lagos were evaluated for the presence of 13 hr HPV genotypes by polymerase chain reaction based assay. Results: The prevalence of high-risk HPV was 19.6% in the studied population. HPV 16 (3.9%), 35 (3.5%), 58 (3.3%) and 31 (3.3%) were the most common hr HPV infections detected. We observed that the prevalence of hr HPV was higher in HIV positives (24.5%) than 15.9% in HIV negative women (OR = 1.7; 95% CI: 1.1-2.7). A multivariate logistic regression analysis showed a lower hr HPV prevalence in HIV positive women on antiretroviral drugs (OR = 0.4; 95% CI: 0.3-0.5) and with CD4 count of 500 and above (OR = 0.7; 95% CI: 0.5-0.8). A higher prevalence of hr HPV was also noted in HIV positive women with CD4 count <200 cells/mm3 (OR = 2.4; 95% CI: 1.7-5.9). Conclusion: HPV 16, 35, 58 and 31 genotypes were the most common hr HPV infection in our study group, which could be regarded as high risk general population sample; with higher prevalence of HPV 16 and 35 in HIV positive women than in HIV negative women. The use of antiretroviral drugs was found to be associated with a lower prevalence of hr HPV infection, compared to those not on treatment. This study raises important issues that should be further investigated to enable the development of robust cervical cancer prevention and control strategies for women in our setting

Detection of adeno-associated virus type 2 genome in cervical carcinoma

Adeno-associated virus (AAV) can impair the replication of other viruses. Adeno-associated virus seroprevalences have been reported to be lower among women with cervical cancer. In-vitro, AAV can interfere with the production of human papillomavirus virions. Adeno-associated virus-2 DNA has also been detected in cervical cancer tissue, although not consistently. To evaluate the role of AAV infection in relation to invasive cervical cancer, we performed a nested case–control study within a retrospectively followed population-based cohort. A total of 104 women who developed invasive cervical cancer on average 5.6 years of follow-up (range: 0.5 months–26.2 years) and 104 matched control-women who did not develop cervical cancer during the same follow-up time were tested for AAV and human papillomavirus by polymerase chain reaction. At baseline, two (2%) case-women and three (3%) control-women were positive for AAV-2 DNA. At the time of cancer diagnosis, 12 (12%) case-women and 3 (3%) matched control-women were positive for AAV-2 DNA. Persisting AAV infection was not evident. In conclusion, AAV-2 DNA was present in a low proportion of cervical cancers and we found no evidence that the presence of AAV in cervical smears of healthy women would be associated with reduced risk of cervical cancer

Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina

BACKGROUND: Infections with high-risk human papillomaviruses (HPVs), causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline) of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype. METHODS: HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I). Fischer's test with Woolf's approximation was used for statistical analysis. RESULTS: HPV DNA was detected in 17 out of 41 (41.5 %) carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas. CONCLUSION: These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas

Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low.</p> <p>Methods</p> <p>Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears.</p> <p>Results</p> <p>Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years). One third of women were HIV infected (283/803; 35.2%) and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; <it>P </it>< 0.001). Of HIV-infected women, 73.3% had high-risk HPV (200/273) and 35.5% had HPV 16 and/or 18 (97/273). Corresponding figures for HIV-negative women were 45.5% (229/503) and 15.7% (79/503). After adjusting for age, number of children and condom use, high-risk HPV was 3.6 fold more common in HIV-infected women (95%CI = 2.6-5.1). Prevalence of all 15 of the high-risk HPV types measured was higher among HIV-infected women, between 1.4 and 5.5 fold. Median total HPV viral load was 881 copies/cell in HIV-infected women (IQR = 33-12,110 copies/cell) and 48 copies/cell in HIV-uninfected women (IQR = 6-756 copies/cell; <it>P </it>< 0.001). HPV 16 and/or HPV 18 were identified in 42.7% of LSIL (32/75) and 42.3% of HSIL (11/26) lesions (<it>P </it>= 0.98). High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75) and HSIL (84.6%; 22/26); even higher among HIV-infected women.</p> <p>Conclusions</p> <p>HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.</p

Role of simian virus 40 in cancer incidence in solid organ transplant patients

Transplant recipients have an increased risk of developing cancer in comparison with the general population. We present here data on cancer development in transplanted subjects who received organs from donors whose DNA was previously examined for the genomic insertion of Simian Virus 40 (SV40). Active follow-up of 387 recipients of solid organs donated by 134 donors, not clinically affected by cancer, was performed through the National Transplant Center (NTC). The average length of follow-up after transplant was 671±219 days (range 0–1085 days). Out of 134 proposed donors, 120 were utilised for organ donation. Of these, 12 (10%) were classified as positive for SV40 genomic insertion. None of the 41 recipients of organs from SV40 positive donors developed a tumour during the follow-up. In all, 11 recipients of organs given by SV40 negative donors developed a tumour (cancer incidence: 0.015 per year). In conclusion, cancer rates observed in our study are comparable to what reported by the literature in transplanted patients. Recipients of solid organs from SV40 positive donors do not have an increased risk of cancer after transplant. The role of SV40 in carcinogenesis in transplanted patients may be minimal