Common genetic variants and risk for HPV persistence and progression to cervical cancer.

HPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV) have persistent infection and further develop cervical pre-cancer/cancer compared to the majority of infected individuals who will clear infection.We evaluated 7140 tag single nucleotide polymorphisms (SNPs) from 305 candidate genes hypothesized to be involved in DNA repair, viral infection and cell entry in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 HPV persistent women (median: 25 months), and 425 random controls (RC) from the 10,049 women Guanacaste Costa Rica Natural History study.

Marginal and mixed-effects models in the analysis of human papillomavirus natural history data.

Human papillomavirus (HPV) natural history has several characteristics that, at least from a statistical perspective, are not often encountered elsewhere in infectious disease and cancer research. There are, for example, multiple HPV types, and infection by each HPV type may be considered separate events. Although concurrent infections are common, the prevalence, incidence, and duration/persistence of each individual HPV can be separately measured.

Lack of heterogeneity of HPV16 E7 sequence compared with HPV31 and HPV73 may be related to its unique carcinogenic properties.

To assess the role of human papillomavirus virus (HPV) genetics in cervical lesions, we sequenced the E7 gene of HPV16, 31, or 73 from singly infected women who (1) cleared the infection quickly, (2) had type-specific persistent infection, or (3) progressed to CIN2 or worse lesions. Four of the 296 HPV16 E7 nucleotides were variable, compared with 7 of 296 for HPV31 E7 and 4 of 296 for HPV73 E7. While most of the polymorphisms in HPV31 and -73 resulted in non-synonymous amino acid changes, the polymorphisms in the HPV16 E7 resulted in synonymous changes.

Persistent antibodies to HPV virus-like particles following natural infection are protective against subsequent cervicovaginal infection with related and unrelated HPV.

Whether persistent human papillomavirus (HPV) IgG antibodies following natural infection are protective against subsequent infection is unknown. In a cohort of 508 college women followed for 3 y, persistent seropositivity was defined as the presence of type-specific HPV virus-like particle (VLP) antibodies at > or = 2 consecutive visits 1 y apart. Protection from incident infection with any HPV was conferred by persistent antibodies to HPV16 (p = 0.

Genomic diversity and interspecies host infection of alpha12 Macaca fascicularis papillomaviruses (MfPVs).

Alpha human papillomaviruses (HPVs) are among the most common sexually transmitted agents of which a subset causes cervical neoplasia and cancer in humans. Alpha-PVs have also been identified in non-human primates although few studies have systematically characterized such types. We cloned and characterized 10 distinct types of PVs from exfoliated cervicovaginal cells from different populations of female cynomolgus macaques (Macaca fascicularis) originating from China and Indonesia.

Human papillomaviruses: genetic basis of carcinogenicity.

Persistent infection by specific oncogenic human papillomaviruses (HPVs) is established as the necessary cause of cervix cancer. DNA sequence differences between HPV genomes determine whether an HPV has the potential to cause cancer. Of the more than 100 HPV genotypes characterized at the genetic level, at least 15 are associated, to varying degrees, with cervical cancer.

Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent.

Background: Antiproliferative effects of proteasome inhibitors are suggested to be primarily due to effects on nuclear factor-kappaB (NF-kappaB)-dependent pathways and the induction of apoptosis. The objective of this study was to elucidate the mechanistic basis for the antiproliferative effects of the proteasome inhibitor, bortezomib, in human clear cell renal cell cancer cells (CCRCC).

Materials And Methods: von Hippel Lindau (VHL) mutation/methylation status and cytotoxic response to bortezomib was determined in a panel of CCRCC cell lines.

Short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study.

Objective: To evaluate the cumulative incidence of cervical intraepithelial neoplasia II or worse (grade II+) or cervical intraepithelial neoplasia grade III+ after short term persistence of prevalently detected carcinogenic human papillomavirus (HPV).

Design: Population based cohort study.

Setting: Guanacaste, Costa Rica.

Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography.

Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia.

Purpose: Infection with oncogenic human papillomaviruses has been linked to the development of cervical neoplasia and cancer. The exclusive expression of E7, a viral oncogene, in infected cells makes this protein an ideal target for immunotherapy. We recently reported on the results of a trial in women with cervical carcinoma-in-situ using HspE7, a protein vaccine consisting of full length HPV16 E7 linked to a heat shock protein from M.

Identification of unusual E6 and E7 proteins within avian papillomaviruses: cellular localization, biophysical characterization, and phylogenetic analysis.

Papillomaviruses (PVs) are a large family of small DNA viruses infecting mammals, reptiles, and birds. PV infection induces cell proliferation that may lead to the formation of orogenital or skin tumors. PV-induced cell proliferation has been related mainly to the expression of two small oncoproteins, E6 and E7.

Treatability by cryotherapy in a screen-and-treat strategy.

Objectives: We estimated the percentage of women infected with human papillomavirus (HPV+) who cannot be immediately treated with cryotherapy.

Materials And Methods: In a 10,000-woman Costa Rican cohort, we analyzed the 559 HPV+ women aged 25 to 55 years and estimated the proportion for whom immediate cryotherapy was not indicated (i.e.

An evaluation by midwives and gynecologists of treatability of cervical lesions by cryotherapy among human papillomavirus-positive women.

Objectives: To estimate efficacy of a visual triage of human papillomavirus (HPV)-positive women to either immediate cryotherapy or referral if not treatable (eg, invasive cancer, large precancers).

Methods: We evaluated visual triage in the HPV-positive women aged 25 to 55 years from the 10,000-woman Guanacaste Cohort Study (n = 552). Twelve Peruvian midwives and 5 international gynecologists assessed treatability by cryotherapy using digitized high-resolution cervical images taken at enrollment.

A recessive gene for primary vesicoureteral reflux maps to chromosome 12p11-q13.

Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR.

Human papillomavirus infection and cervical cytology in HIV-infected and HIV-uninfected Rwandan women.

Background: Data on human papillomavirus (HPV) prevalence are essential for developing cost-effective cervical cancer prevention programs.

Methods: In 2005, 710 human immunodeficiency virus (HIV)-positive and 226 HIV-negative Rwandan women enrolled in an observational prospective cohort study. Sociodemographic data, CD4+ cell counts, and cervical specimens were obtained.

Common genetic variation in TP53 and risk of human papillomavirus persistence and progression to CIN3/cancer revisited.

Driven by findings that human papillomavirus (HPV)-induced degradation of p53 differs by a TP53 polymorphism at codon 72 (Pro72Arg), past studies of TP53 genetic variants and cervical cancer have focused on this nonsynonymous polymorphism, with mixed results. We analyzed common single nucleotide polymorphisms (SNP) across the TP53 locus in a population-based nested case-control study in Guanacaste, Costa Rica. We evaluated 11 SNPs, including Pro72Arg (rs1042522), among 1,281 women: 465 with cervical intraepithelial neoplasia grade 3/cancer (CIN3+), 380 with HPV persistence (median, 25 months), and 436 random population controls.

Illumina DNA test panel-based genotyping of whole genome amplified-DNA extracted from hair samples: performance and agreement with genotyping results from genomic DNA from buccal cells.

Background: Hair is a DNA source that can be collected easily and inexpensively from participants in epidemiological studies. However, there is concern about DNA quality and quantity. Therefore, we assessed genotyping performance of whole genome amplified (WGA)-DNA extracted from hair using the GenomePlex method and evaluated its agreement with genotyping results of buccal cell DNA from the same individuals, using the Illumina GoldenGate platform.

Diagnosis of palmar hyperhidrosis via questionnaire without physical examination.

Objectives: In order to determine the reliability of a self-administered instrument to diagnose excessive sweating conditions, including palmar hyperhidrosis (PH), we designed two successive questionnaires and compared responses with physical examination and sweat measurement in normal volunteers and a cohort of patients with documented PH. The reliable diagnosis of PH via questionnaire would enable molecular epidemiological studies without the need for physical examination or direct sweat measurement.

Methods: Subjects self identified as either normal or affected by PH.

Human papillomavirus types by age in cervical cancer precursors: predominance of human papillomavirus 16 in young women.

In a population-based study conducted in Guanacaste, Costa Rica, we investigated the human papillomavirus (HPV) types detected in 233 cases of cervical intraepithelial neoplasia (CIN) 2/3 and cancer by age. CIN2+ and CIN3+ in young women were significantly more likely to be associated with HPV 16 than the same lesions in older women (80% of CIN3+ were associated with HPV 16 among women ages 18-26 years compared with only 32% among women older than 55 years; Ptrend=0.018).

Evolutionary and biophysical relationships among the papillomavirus E2 proteins.

Infection by human papillomavirus (HPV) may result in clinical conditions ranging from benign warts to invasive cancer. The HPV E2 protein represses oncoprotein transcription and is required for viral replication. HPV E2 binds to palindromic DNA sequences of highly conserved four base pair sequences flanking an identical length variable 'spacer'.

Solid phase extraction of polyhalogenated pollutants from freshwater using chemically modified multi-walled carbon nanotubes and their determination by gas chromatography.

This paper describes the application of pristine and chemically modified multi-walled carbon nanotubes (MWCNTs) as packing materials for the preconcentration and determination of various polyhalogenated organic pollutants, pentachlorophenol, 2,4,5-trichlorophenol, 3,3',4,4'-tetrachlorobiphenyl, and 2,2',5,5'-tetrabromobiphenyl from real water samples based on solid-phase extraction. MWCNTs were chemically modified by octadecyl amine and polyethylene glycol, separately, and the resulting nano materials were used as packing materials for solid phase extraction. Method development, applicability, and suitability of the above mentioned adsorbents for the solid phase extraction were studied.

Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations.

Purpose: Protein-truncating mutations in BRCA1 and in particular BRCA2 genes have been associated with prostate cancer. However, there is still uncertainty about the magnitude of association particularly with Gleason score, and family history of prostate, breast, and ovary cancers.

Experimental Design: To further examine associations between three founder mutations located in BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) genes and prostate cancer, we conducted a study of 979 prostate cancer cases and 1,251 controls among Ashkenazi Jewish men.

Genetic variants in TAP are associated with high-grade cervical neoplasia.

Purpose: The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections.

Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma.

Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction.

Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women.

Background: The positive association between obesity and postmenopausal breast cancer has been attributed, in part, to the fact that estrogen, a risk factor for breast cancer, is synthesized in adipose tissue. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed associations between circulating levels of insulin and/or insulin-like growth factor (IGF)-I, a related hormone, and the risk of breast cancer independent of estrogen level.