Nancy B Kiviat

University of Washington Seattle | UW · Department of Pathology

Background: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. Methods: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV neg...

Introduction: Programmatic treatment outcome data for people living with HIV-2 in West Africa, where the virus is most prevalent, are scarce. Methods: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this prospective, longitudinal observational cohort study. We analyzed...

Background: Despite a reduction in the prevalence of vaccine-preventable types of human papillomavirus (HPV), attributed to increased HPV vaccine uptake, HPV continues to be a major cause of cancer in the United States. Methods: We assessed factors associated with self-reported HPV vaccine uptake, HPV vaccination effectiveness, using DNA testing t...

: le VIH-2, endémique en Afrique de l'Ouest, est naturellement résistant aux inhibiteurs non nucléosidiques de la rétro transcriptase (INNRTI), ce qui rend difficile la prise en charge dans les pays en développement. L'objectif ici était de déterminé la prévalence de l'échec virologique au 12éme et 24éme mois (M12 et M24) de traitement antirétrovir...

Background: Epidemiologic data addressing clinical relevance of viral load fluctuation of oncogenic types other than human papillomavirus (HPV) types 16 and 18 are limited. Methods: A type-stratified set of infections by non-HPV16/18 oncogenic types that were detected at ≥2 visits was randomly selected from women who were enrolled in a clinical...

Objectives: The objectives of this study were to: I) discover novel human papillomaviruses (HPVs) using next generation sequencing (NGS) technology in oral rinse samples collected from oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients; II) determine the prevalence of novel HPVs in archived OCC and OPC tissue samples; and III) examin...

[This corrects the article DOI: 10.1371/journal.pone.0208635.].

Background Non-communicable diseases, including hypertension (HTN), are increasingly recognized as important causes of morbidity and mortality among people living with HIV (PLHIV) in resource-limited settings. The goals of this study were to determine the prevalence of HTN among PLHIV in Senegal over time and to identify predictors of HTN among HIV...

Table A: Description of parent studies. Table B: Parent study aims and subjects. (DOCX)

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub‐Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial canc...

The aims of this study were to determine the nutritional status of HIV-positive versus HIV-negative adults in Senegal and to identify predictors of nutritional status among people living with HIV (PLHIV). We conducted a retrospective study using data from individuals enrolled in previous studies in Senegal. Undernutrition was defined as body mass i...

Background: There is evidence of an interaction between HIV and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status.Methods:A total of 1,320 women (47% were positive for HIV-1 and...

Background: To evaluate clinician and patient attitudes toward home self-collected human papillomavirus (HPV) testing for cervical cancer screening. Methods: Women aged 21-65 years were recruited for a randomized trial comparing home self-collected HPV testing to standard clinician-collected Pap screening. Participants were surveyed about their...

Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study who had ≥1 of 11 non-HPV16/...

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 (called high-risk (HR) variants) compared with non-HR variants. This study w...

Objective: To explore the possibility of single-cell analysis of human papillomavirus (HPV) infection. Methods: Two hundred and twenty cells were isolated by laser capture microdissection from formalin-fixed and paraffin-embedded cervical tissue blocks from 8 women who had HPV DNA detected in their cervical swab samples. The number of type-speci...

Background Due to the increasing rates of oropharyngeal cancer, oral HPV infection is a significant concern. Methods for detecting oral HPVs is not standardized as there are different techniques available. We propose that use of oral rinse samples to detect for HPVs is a suitable technique within a clinic setting. Thus, our main objective is to stu...

In light of observational evidence showing an association between human papillomavirus (HPV) and HIV acquisition risk, the potential of HPV vaccination as a HIV prevention strategy is being considered. However, the relationship between HPV and HIV infectiousness is unclear. In this analysis, the relationship between HPV and anogenital HIV shedding...

In order to elucidate the role of epigenetic alterations in the development of cutaneous squamous cell carcinoma (SCC), we analyzed both gene-specific promoter hypermethylation and repetitive sequence hypomethylation in cutaneous SCC as well as normal skin tissue samples. We showed that methylation of DAPK1 and CDH13 was associated with cutaneous S...

Background: Data on clinical outcomes of infection with variants of oncogenic human papillomavirus (HPV) types other than HPV16 and HPV18 are rare. We investigated intratypic variations in non-HPV16/18 oncogenic types and their corresponding relationships with cervical intraepithelial neoplasia grades 2-3 (CIN2/3). Methods: Study subjects were w...

Background: The importance of human papillomavirus (HPV) viral load in the pathogenesis of cervical cancer among HIV-infected and HIV-uninfected women has not yet been established. Methods: In this cross-sectional study, HPV-16 viral loads were measured using previously-collected and frozen cervical swab samples from 498 HPV-16 positive Senegale...

While infection with high-risk (HR) human papillomavirus (HPV) is central to cervical carcinogenesis, natural history studies show that both low- and high-grade cervical intraepithelial neoplasia (CIN) lesions are very early manifestations of HR-HPV infection. Most high- and low-grade lesions are self limited, and only those HR-HPV infections capab...

An accurate biomarker for the follow-up of women positive for human papillomavirus type 16 (HPV16) DNA may improve the efficiency of cervical cancer prevention. Previously we analyzed all 113 HPV16 CpGs in cervical cytology samples and discovered differential methylation at different stages of premalignancy. In the current study, we identified a me...

Despite the strong evidence of HPV infection as the etiological agent in a subset of oral cancer, oral α-HPV detection is rare in healthy individuals, and little is known of the existing of novel HPV types in oral cavity. We determined whether novel HPV types can be isolated from oral rinse samples collected from healthy individuals. We performed r...

Protease inhibitor (PI)-based antiretroviral therapy (ART) can effectively suppress HIV-2 plasma load and increase CD4 counts; however, not all PIs are equally active against HIV-2, and few data exist to support second-line therapy decisions. To identify therapeutic options for HIV-2 patients failing ART, we evaluated the frequency of PI resistance...

Objective: Dual infection with HIV-1 and HIV-2, which is not uncommon in West Africa, has implications for transmission, progression, and antiretroviral therapy (ART). Few studies have examined viral dynamics in this setting. Our objective was to directly compare HIV-1 and HIV-2 viral loads and to examine whether this relationship is associated wi...

We estimated type-specific prevalence of human papillomavirus (HPV) and examined risk factors for abnormal cervical cytology among 296 female sex workers from Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1 sero-positivity was associat...

Variants of human papillomavirus (HPV) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. It is largely undetermined whether variants differ in their likelihood of persistence. Study subjects were women who participated in the ASCUS-LSIL Triage Study and who had a newly detected HPV31 infe...

Background: Cervical cancer is a major public health problem for women in sub-Saharan Africa. Availability of a human papillomavirus (HPV) vaccine could have an important public health impact. Methods: In this phase IIIb, double-blind, randomized, placebo-controlled, multicenter trial (NCT00481767), healthy African girls and young women seronega...

The association between human papillomavirus type 31 (HPV31) DNA load and risk of cervical intraepithelial neoplasia 2-3 (CIN2-3) was evaluated among women enrolled in the ASCUS-LSIL Triage Study who were followed semi-annually over 2 years and who had HPV31 infections detected at ≥1 visit. HPV31 DNA loads in the first HPV31-positive samples and in...

The epidemiology of high-risk (hr) human papillomavirus (HPV) infections in mid-adult women with new sex partners is undefined. We analyzed baseline data from 518 25- to 65-year-old women online daters. Women were mailed questionnaires and kits for self-collecting vaginal specimens for polymerase chain reaction-based hrHPV testing. Risk factors for...

We assessed trends in the relative prevalences of HIV-1, HIV-2 and dual HIV-1/HIV-2 infection in 10,321 women attending outpatient clinics in Senegal between 1990 and 2009. The relative prevalence of HIV-1 (defined as the proportion of seropositive subjects having HIV-1) rose sharply from 38% in 1990 until 1993 (P < 0.001), whereupon it continued t...

MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of m...

miRNA expression in HOSE cell lines, normal ovaries, and benign ovarian tumors. Expression of miR-181d, miR-368, and miR-370 was significantly different between cell lines and normal ovaries as well as between cell lines and benign tumors. In addition, expression of miR-30c and miR-30e-3p was significantly different between cell lines and normal ov...

A survey was administered to male university students who tested positive for high-risk human papillomavirus. Disclosure was more likely in men with fewer partners, in main partnerships, and in longer partnerships. Disclosure was associated with discussing the Pap test/human papillomavirus vaccine with female partners and not associated with a wors...

Optimal care of persons infected with human immunodeficiency virus type 2 (HIV-2) requires an accurate assessment of HIV-2 plasma viral load (VL), but no clinically approved quantitative HIV-2 RNA VL assay exists. To validate a novel quantitative HIV-2 RNA assay for clinical and research use. The Abbott m2000sp/rt platform was adapted for quantific...

To investigate the role of immunological parameters in tumorigenesis of cervical cancer in women infected with high risk human papillomavirus (hr-HPV), and determine whether key findings with human material can be recapitulated in the mouse TC1 carcinoma model which expresses hr-HPV epitopes. Epithelial and lymphoid cells in cervical tissues were a...

Background: Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However,...

To quantify the prevalence and burden of HIV type 2 (HIV-2) and HIV-1 RNA in the oral cavity of antiretroviral therapy-naive HIV-infected Senegalese individuals and to identify correlates of oral HIV viral loads. A cross-sectional study of 163 HIV-1 and 27 HIV-2-infected antiretroviral therapy-naive Senegalese adults. Participants received clinical...

Compared with human immunodeficiency virus type 1 (HIV-1), little is known about the susceptibility of HIV-2 to antibody neutralization. We characterized the potency and breadth of neutralizing antibody (NAb) responses in 64 subjects chronically infected with HIV-2 against three primary HIV-2 strains: HIV-2(7312A), HIV-2(ST), and HIV-2(UC1). Surpri...

MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to...

Raltegravir is the first integrase strand transfer inhibitor approved for treating HIV-1 infection. Although emerging data suggest that raltegravir may also be useful for HIV-2 treatment, studies addressing the in-vitro susceptibility of HIV-2 to raltegravir are scarce, and the genetic pathways leading to raltegravir resistance in HIV-2 have not be...

The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin structure, which is regulated by DNA methylation and histone modification, is at the center of gene regulation. Immunoprecipitations of chr...

While previous studies have investigated the utility of Luminex technology in comparison to other standard techniques, there have been few studies directly comparing different bead-based assays. A key barrier to establishing Luminex technology in research or clinical laboratories is the apparent need to purchase not only encoded bead sets but also...

The clinical relevance of human papillomavirus type 16 (HPV16) DNA methylation has not been well documented, although its role in modulation of viral transcription is recognized. Study subjects were 211 women attending Planned Parenthood clinics in Western Washington for routine Papanicolaou screening who were HPV16 positive at the screening and/or...

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integras...

Viral load may influence the course of human papillomavirus type 16 (HPV-16) infection. This case-control study was nested within the 2-year Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study, in which women were followed semiannually for HPV and cervical intraepithelial neoplasia (CIN)....

Human gammadelta (γδ) T cells play an important role in protective immunity in HIV-1 and simian immunodeficiency virus infection; their role in HIV-2 infection is unknown. To determine the role of γδ T cells in control of plasma viral load and CD4 T-cell count in HIV-1 and HIV-2 infections in West Africa. Thirty HIV-1 and 25 HIV-2 treatment-naive c...

DNA methylation analysis is emerging as a new technique with potential capabilities for early cancer detection. However, current state-of-the-art techniques are not easily translatable into routine clinical methods. Herein we describe a bead-based flow cytometry assay which combines DNA hybridization to microparticles with 5MeC-specific proteins/an...

It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be h...

To identify sensitive and specific histological criteria for endometritis in women with laparoscopically-confirmed acute salpingitis. Women, age 18-40 years of age presenting with complaints of lower abdominal pain ≤2 weeks and no antibiotics use in past two weeks, were enrolled. They underwent clinical examination, screening for HIV; other sexuall...

Characterizing short-term detection patterns of young women's incident α-genus human papillomavirus (HPV) infections may further our understanding of HPV transmission. Between 2000 and 2007, we followed 18- to 22-year-old female university students with triannual HPV DNA and Papanicolaou testing. Using Kaplan-Meier methods, we estimated duration of...

Prospective studies of the persistence of human papilloma-virus (HPV) variants are rare and typically small. We sequenced HPV-16 variants in longitudinal pairs of specimens from 86 women enrolled in the ASCUS-LSIL Triage Study. A change of variants was identified in 4 women (4.7% [95% confidence interval, 1.3%-11.5%]). Among women with intervening...

We determined the feasibility of human papillomavirus (HPV) detection in cervical exfoliated cells collected as dry swab samples. Both dry cervical swab and specimen transport medium (STM) cervical swab samples were collected from 135 patients attending either colposcopy or women's clinics in Guayaquil, Ecuador, who had a cytology diagnosis within...

During the last 20 years, we have greatly expanded our understanding of cervical cancer pathogenesis. Epidemiological and laboratory-based studies have definitively demonstrated that infection with “high risk” (HR) or oncogenic types of human papillomavirus (HPV) is central to, and necessary for, development of squamous and endocervical cancers of...

Little is known about detection of genital human papilloma virus (HPV) types in women's fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and the agreement between fingertip and genital samples for detecting HPV. At triannual visits, genital and fingertip samples were collected from female uni...

Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk human papillomavirus (HPV) DNA testing of self-collected vaginal samples. A subset of 1,665 women (age range, 18-50 y) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of b...

Hepatocellular carcinoma (HCC) is known to be associated with both HBV and HCV. While epigenetic changes have been previously reported to be associated with hepatocellular carcinoma (HCC), whether the epigenetic profile of HBC associated HCC differs from that of HCV-associated HCC is unclear. We analyzed DNA methylation of ten genes (APC, CCND2, CD...

Studies of viral load-associated persistence of human papillomavirus (HPV) infection are rare, with inconsistent results reported. The study subjects were 741 and 289 women who were positive for HPV type 16 (HPV-16) and HPV type 18 (HPV-18), respectively, at the time of enrollment into in the ASCUS-LSIL (Atypical Squamous Cells of Undetermined Sign...

The low sensitivity of cytology and low specificity of human papillomavirus testing prompts searching for more accurate cervical cancer screening strategies. Our goal was to evaluate an ELISA-based test for p16(INK4a). 1,781 women undergoing routine screening provided cervical specimens for p16(INK4a) ELISA (original and enhanced versions of a prot...

We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better...

Cervical cancer is the second leading cause of cancer mortality in women worldwide, and the leading cause in Africa. There is uncertainty in the role of HIV infection as a risk factor for invasive and preinvasive cervical lesions, particularly in African populations. In a case-control study in Dakar, Senegal, we studied 150 women with invasive cerv...

Intratypic diversity of human papillomavirus (HPV) genome is generally characterized by point mutation, insertion, and/or deletion. Using PCR-based cloning and sequencing, we detected concurrent infection with 8 HPV16 variants in a woman enrolled in the ASCUS-LSIL Triage Study. The European variant was the major variant; each of the 7 minor variant...

The objective of the study was to examine the relationship of depot-medroxyprogesterone acetate (DMPA) and combined oral contraceptive (COC) use with cervical intraepithelial neoplasia (CIN). Two case-control studies of women who presented for gynecologic care and underwent cytologic and human papillomavirus (HPV) testing were performed. The first...

Herein we report a method for the detection of methylated CpG dinucleotides located within CpG islands in genomic DNA using multiplexed bead-based assays and standard flow cytometry instrumentation. Four CpG "clusters" were identified in the TFPI2 and SPARC CpG islands whose methylation status was highly correlated with the incidence of invasive ce...

Human papillomavirus (HPV) RNA levels may be a more sensitive early indicator of predisposition to carcinogenesis than DNA levels. We evaluated whether levels of HPV-16 and HPV-18 DNA and messenger RNA (mRNA) in newly detected infections are associated with cervical lesion development. Female university students were recruited from 1990 to 2004. Ce...

Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysiologic process of recruitment of...

Vulvar/vaginal human papillomavirus (HPV) infections may precede cervical infections, and certain low-risk types may display vaginal tropism. We evaluated whether incident infections in young women display site-specific preferences by HPV risk group or phylogenetic species. Although incident infections were more likely to be detected in the vulva/v...

The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HI...

We developed a liquid bead microarray (LBMA) assay for genotyping genital human papillomaviruses (HPVs) based on the MY09-MY11-HMB01 PCR system and the reverse line blot (RLB) assay probe sequences. Using individual HPV plasmids, we were able to detect as few as 50 copies per reaction. In two separate retrospective studies, the LBMA assay was compa...

Given that the integration of human papillomavirus type 16 (HPV16) into the host genome occurs preferentially with the disruption of the E2 gene, a ratio of E2 to E7 gene copies is often used as a marker for integration. It is largely undetermined, however, whether ratio estimates are affected by HPV intratypic variations. We assembled four plasmid...

The clinical relevance of the amount of human papillomavirus type 18 (HPV18) DNA in cervical tissue (ie, HPV18 DNA load) is unknown. Study subjects were 303 women who were HPV18 positive at enrollment into the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. HPV18 DNA l...