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1.  Variants in Interleukin Family of Cytokines Genes Influence Clearance of High Risk HPV in HIV-1 Coinfected African-American Adolescents 
Human immunology  2013;74(12):10.1016/j.humimm.2013.08.010.
Our work aimed to examine the potential influence of variants in interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance. Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive African-American female adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single nucleotide polymorphisms (SNPs) within the exons, 5′ untranslated region (UTR) and 3′ UTR sequences of 27 immune-related candidate genes encoding interleukin family of cytokines. Cox proportional hazard models were used to determine the association of type- specific HPV clearance adjusting for time-varying CD4+ T-cell count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were significantly (p< 0.001) associated with five SNPs (rs228942, rs419598, rs315950, rs7737000, rs9292618) mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed genetic variants in interleukin family of cytokines modulate HR-HPV clearance in HIV-1 seropositive African-Americans that warrants replication.
doi:10.1016/j.humimm.2013.08.010
PMCID: PMC3842375  PMID: 23973891
HPV clearance; genetic association; interleukins; HIV-1 seropositive; African American adolescents
2.  Dense Genotyping of Immune-Related Loci Identifies Variants Associated with Clearance of HPV among HIV-Positive Women in the HIV Epidemiology Research Study (HERS) 
PLoS ONE  2014;9(6):e99109.
Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p<10−6). A variant (rs1633038) in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.
doi:10.1371/journal.pone.0099109
PMCID: PMC4053382  PMID: 24918582
3.  Brief Report: Knowledge, attitudes, practices and perceived risk of cervical cancer among Kenyan women 
OBJECTIVES
Eastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer in order to determine target groups to increase cervical cancer screening.
METHOD
In this cross-sectional study we surveyed women seeking reproductive health services in Kisumu, Kenya to assess their perceived risk of cervical cancer and risk factors influencing cervical cancer screening uptake. Chi-square statistics and t-tests were used to determine significant factors, which were incorporated into a logistic model to determine factors independently associated with cervical cancer risk perception.
RESULTS
While 91% of the surveyed women had heard of cancer, only 29% of the 388 surveyed women had previously heard of cervical cancer. The majority had received their information from healthcare workers. Few women (6%) had ever been screened for cervical cancer and cited barriers such as fear, time, and lacking knowledge about cervical cancer. Nearly all previously screened women (22/24, 92%) believed that cervical cancer was curable if detected early, and that screening should be conducted annually (86%). Most women (254/388, 65%) felt they were at risk for cervical cancer. Women with perceived risk of cervical cancer were older (OR=1.06, 95% CI 1.02, 1.10), reported a history of marriage (OR=2.08, CI 1.00, 4.30), were less likely to feel adequately informed about cervical cancer by healthcare providers (OR= 0.76, CI 0.18, 0.83) and more likely to intend to have cervical cancer screening in the future (OR= 10.59, CI 3.96, 28.30). Only 5% of women reported that they would not be willing to undergo screening, regardless of cost.
Conclusions
Cervical cancer is a major health burden for women in sub-Saharan Africa, yet only one-third of women had ever heard of cervical cancer in Kisumu, Kenya. Understanding factors associated with women’s perceived risk of cervical cancer could guide future educational and clinical interventions to increase cervical cancer screening.
doi:10.1097/IGC.0b013e31828e425c
PMCID: PMC3662490  PMID: 23694983
Screening; Barriers; Cervical Cancer; Africa
4.  Role and uptake of human papillomavirus vaccine in adolescent health in the United States 
Both the prophylactic human papillomavirus (HPV) vaccines, Gardasil® and Cervarix®, are licensed for the prevention of cervical cancer in females, and Gardasil is also licensed for the prevention of genital warts and anal cancer in both males and females. This review focuses on the uptake of these vaccines in adolescent males and females in the USA and the barriers associated with vaccine initiation and completion. In the USA in 2009, approximately 44.3% of adolescent females aged 13–17 years had received at least one dose of the HPV vaccine, but only 26.7% had received all three doses. In general, the Northeast and Midwest regions of the USA have the highest rates of HPV vaccine initiation in adolescent females, while the Southeast has the lowest rates of vaccine initiation. Uptake of the first dose of the HPV vaccine in adolescent females did not vary by race/ethnicity; however, completion of all three doses is lower among African Americans (23.1%) and Latinos (23.4%) compared with Caucasians (29.3%). At present, vaccination rates among adolescent females are lower than expected, and thus vaccine models suggest that it is more cost-effective to vaccinate both adolescent males and females. Current guidelines for HPV vaccination in adolescent males is recommended only for “permissive use,” which leaves this population out of routine vaccination for HPV. The uptake of the vaccine is challenged by the high cost, feasibility, and logistics of three-dose deliveries. The biggest impact on acceptability of the vaccine is by adolescents, physicians, parents, and the community. Future efforts need to focus on HPV vaccine education among adolescents and decreasing the barriers associated with poor vaccine uptake and completion in adolescents before their sexual debut, but Papanicolau screening should remain routine among adults and those already infected until a therapeutic vaccine can be developed.
doi:10.2147/AHMT.S15941
PMCID: PMC3804132  PMID: 24155627
human papillomavirus; vaccine uptake; adolescent health
5.  Incidence, Prevalence and Epidemiology of Herpes Simplex Virus-2 in HIV-1-positive and HIV-1-negative Adolescents 
Sexually Transmitted Diseases  2012;39(4):300-305.
Background
Several studies have assessed risk factors associated with herpes simplex virus-2 (HSV-2) prevalence in adults; however, few have focused on HSV-2 incidence, particularly in adolescents. The objective of this study was to determine HSV-2 prevalence and incidence and associated risk factors in a HIV-1-positive and at risk HIV-1-negative adolescent population.
Methods
Sera were tested for HSV-2 antibodies in 518 adolescents in the Reaching for Excellence in Adolescent Care and Health (REACH) cohort at baseline and again at the final follow-up visit. Prevalence at baseline and incidence (per person years) of HSV-2 infection were calculated. Furthermore, among HIV-1-positive individuals, a subgroup analysis was performed to assess risk factors for HSV-2 infection. Conditional logistic regression was used to estimate odds ratios (OR) and p-values (p) for associations between CD4+ T-cell (CD4+) count, HIV-1 viral load (VL), and HSV-2 acquisition, adjusting for antiretroviral therapy use, other sexually transmitted infections, gender, race, and number of sexual partners.
Results
At baseline, 179 (35%) subjects were HSV-2 positive, with an additional 47 (16%) new cases being identified during a median follow-up time of 1.95 years and an incidence rate of 7.35 cases per 100 person years (py). Several risk factors were associated with HSV-2 prevalence (being female, non-Hispanic, uncertainty of sexual preference, and HIV-1 positive) and incidence (using drugs, alcohol, and number of new sexual partners). Among HIV-1 positives, an increase in CD4+ count by 50 cell/mm3 (OR, 1.17; 95% CI 1.04–1.31, p=0.008) was associated with HSV-2 acquisition.
Conclusions
The high prevalence and incidence of HSV-2 infection among adolescents, compared to the general population at this age group suggests a critical need for screening and preventive programs among this targeted group.
doi:10.1097/OLQ.0b013e318244a90f
PMCID: PMC3306602  PMID: 22421698
HIV-1; HSV-2; CD4+ count; adolescents
6.  Transitional Probability-Based Model for HPV Clearance in HIV-1-Positive Adolescent Females 
PLoS ONE  2012;7(1):e30736.
Background
HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals).
Methodology and Findings
Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm3, p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm3). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection.
Conclusions
This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.
doi:10.1371/journal.pone.0030736
PMCID: PMC3265500  PMID: 22292027
7.  Role and uptake of human papillomavirus vaccine in adolescent health in the United States 
Both the prophylactic human papillomavirus (HPV) vaccines, Gardasil® and Cervarix®, are licensed for the prevention of cervical cancer in females, and Gardasil is also licensed for the prevention of genital warts and anal cancer in both males and females. This review focuses on the uptake of these vaccines in adolescent males and females in the USA and the barriers associated with vaccine initiation and completion. In the USA in 2009, approximately 44.3% of adolescent females aged 13–17 years had received at least one dose of the HPV vaccine, but only 26.7% had received all three doses. In general, the Northeast and Midwest regions of the USA have the highest rates of HPV vaccine initiation in adolescent females, while the Southeast has the lowest rates of vaccine initiation. Uptake of the first dose of the HPV vaccine in adolescent females did not vary by race/ethnicity; however, completion of all three doses is lower among African Americans (23.1%) and Latinos (23.4%) compared with Caucasians (29.3%). At present, vaccination rates among adolescent females are lower than expected, and thus vaccine models suggest that it is more cost-effective to vaccinate both adolescent males and females. Current guidelines for HPV vaccination in adolescent males is recommended only for “permissive use,” which leaves this population out of routine vaccination for HPV. The uptake of the vaccine is challenged by the high cost, feasibility, and logistics of three-dose deliveries. The biggest impact on acceptability of the vaccine is by adolescents, physicians, parents, and the community. Future efforts need to focus on HPV vaccine education among adolescents and decreasing the barriers associated with poor vaccine uptake and completion in adolescents before their sexual debut, but Papanicolau screening should remain routine among adults and those already infected until a therapeutic vaccine can be developed.
doi:10.2147/AHMT.S15941
PMCID: PMC3804132  PMID: 24155627
human papillomavirus; vaccine uptake; adolescent health
8.  The impact of highly active antiretroviral therapy on prevalence and incidence of cervical human papillomavirus infections in HIV-positive adolescents 
BMC Infectious Diseases  2010;10:295.
Background
The implementation of highly active antiretroviral therapy (HAART) among HIV-positive patients results in immune reconstitution, slower progression of HIV disease, and a decrease in the occurrence of opportunistic infections. However, the impact of HAART on cervical human papillomavirus (HPV) infection, clearance, and persistence in high-risk adolescents remains controversial.
Methods
HIV-positive and high-risk HIV-negative female adolescents were enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) longitudinal cohort study. At each semi-annual clinical visit, cervical lavage samples were tested for 30 HPV types. Type-specific and carcinogenic risk-specific HPV prevalence and incidence were compared in 373 eligible participants: 146 HIV-negative female adolescents with a median follow-up of 721.5 [IQR: 483-1301] days and 227 HIV-positive female adolescents. Of the 227 HIV-positive participants, a fixed set (n = 100) were examined both before and after HAART initiation; 70 were examined only before HAART initiation; and 57 were examined only after HAART initiation, with overall median follow-up of 271 [IQR: 86.5-473] and 427.25 [IQR: 200-871] days respectively for before and after HAART initiation.
Results
Of the 373 eligible participants, 262 (70%) were infected with at least one type of HPV at baseline, and 78 of the remaining 111 (70%) became infected with at least one type of HPV by the end of the study. Overall, the incidence and prevalence of HPV types 58, 53/66, 68/70, and 31/33/35 were much higher than the established carcinogenic and HPV vaccine types 16 and 18, especially in HIV-positive females both before and after HAART initiation. Baseline prevalence for individual high-risk HPV types ranged, depending on type, from 0.7-10%, 1-17%, and 1-18% in the HIV-negative group, the HIV-positive before HAART initiation group, and the HIV-positive after HAART initiation group, respectively. Likewise, the incidence ranged, depending on HPV type, from 0.64-9.83 cases/100 PY, 3.00-12.80 cases/100 PY, and 1.49-17.05 cases/100 PY in the three groups, respectively. The patterns of each HPV type infection, clearance, and persistence did not differ considerably before or after the introduction of HAART and were clearly independent of CD4+ change within the short post-HAART follow-up period.
Conclusions
HAART did not immediately affect the incidence of type-specific HPV infections within a short-period follow-up; however, future studies are warranted in larger populations to evaluate HAART's impact over longer periods.
doi:10.1186/1471-2334-10-295
PMCID: PMC2965148  PMID: 20946655

Results 1-9 (9)