Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 39 Records) |
Query Trace: Panicker G[original query] |
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WHO International Standards for antibodies to HPV6 HPV11 HPV31 HPV33 HPV45 HPV52 and HPV58
Kemp TJ , Panicker G , Eklund C , Nie J , Wang Y , Beddows S , Rigsby P , Huang W , Dillner J , Unger ER , Pinto LA , Wilkinson DE . NPJ Vaccines 2024 9 (1) 165 Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays. |
Immunogenicity of quadrivalent human papillomavirus vaccine among Alaska Native children aged 9-14 years at 5 years after vaccination
Davis BM , Blake I , Panicker G , Meites E , Thompson G , Geis J , Bruden D , Fischer M , Singleton R , Unger ER , Markowitz LE , Bruce MG . Vaccine 2024 BACKGROUND: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. METHODS: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). RESULTS: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. CONCLUSIONS: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination. |
Immunogenicity of 2 or 3 doses of 9vHPV vaccine in U.S. female individuals 15 to 26 years of age
Berenson AB , Panicker G , Unger ER , Rupp RE , Kuo YF . NEJM Evid 2024 3 (2) EVIDoa2300194 Immunogenicity of Two or Three Doses of 9vHPV VaccineThis noninferiority trial examined two versus three doses of 9-valent human papillomavirus (9vHPV) vaccine in individuals 15 to 26 years of age in the United States. In an unplanned interim analysis of female participants, two doses of 9vHPV vaccine appeared to elicit similar rates of seroconversion and antibody titers for each of the nine HPV genotypes to three doses at 1 month postvaccination. |
Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine
Bhatla N , Muwonge R , Malvi SG , Joshi S , Poli URR , Lucas E , Esmy PO , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Vashist S , Mishra G , Jadhav R , Siddiqi M , Anantharaman D , Panicker G , Butt J , Sankaran S , Kannan Tpra , Varghese R , Kartha P , Pillai MR , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Hum Vaccin Immunother 2023 19 (3) 2289242 Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier. |
Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study
Téblick L , Pattyn J , Van Keer S , De Smet A , De Coster I , Tjalma WAA , Rajbhandari I , Panicker G , Unger ER , Vorsters A . J Med Virol 2023 95 (10) e29133 Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first-void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first-void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type-specific antibody responses to the 9vHPV types were analyzed in 174 first-void urine and 172 serum samples using a virus-like particle-based IgG multiplex enzyme-linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%-100% of first-void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%-100% of first-void urine and 98%-100% of serum samples had HPV-specific antibody concentrations. Results show significant Spearman rank correlations between type-specific HPV-antibody concentrations for paired first-void urine and serum at all time points. This study confirms the potential feasibility of utilizing first-void urine as a noninvasive immunological sample within HPV vaccine trials. |
Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination
Joshi S , Anantharaman D , Muwonge R , Bhatla N , Panicker G , Butt J , Rani Reddy Poli U , Malvi SG , Esmy PO , Lucas E , Verma Y , Shah A , Zomawia E , Pimple S , Jayant K , Hingmire S , Chiwate A , Divate U , Vashist S , Mishra G , Jadhav R , Siddiqi M , Sankaran S , Pillai Rameshwari Ammal Kannan T , Kartha P , Shastri SS , Sauvaget C , Radhakrishna Pillai M , Waterboer T , Müller M , Sehr P , Unger ER , Sankaranarayanan R , Basu P . Vaccine 2022 41 (1) 236-245 BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination. |
Enhanced immunogenicity of adjuvanted microparticulate HPV16 vaccines administered via the transdermal route
Vo TP , Panicker G , Braz-Gomes K , Parenky AC , Rajbhandari I , Rajeevan MS , Unger ER , D'Souza MJ , Uddin MN . Pharmaceuticals (Basel) 2022 15 (9) Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch(®) and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine. |
Multiplex immunoassay to measure antibody response to nine HPV vaccine types
Panicker G , Rajbhandari I , Pathak HN , Brady AM , Unger ER . J Immunol Methods 2021 498 113136 Well-characterized HPV serology assays are required to evaluate performance of biosimilar candidate vaccines, reduced dosing schedules and novel administration methods. We report characterization of an expanded assay, M9ELISA, that detects antibodies to HPV virus-like particles (VLP) of nine types using direct IgG ELISA on the Meso Scale Discovery (MSD) electrochemiluminescence platform. The method is based on the previously published M4ELISA which detects antibodies to HPV6,11,16, and 18. It has been modified to add detection of antibodies to HPV31,33,45,52 and 58, and to streamline assay and reduce background. The M9ELISA plates were prepared with purified type specific L1 + L2 VLPs coated on 10-spot/well standard MSD microplates. Results of ELISA on three serial dilutions of serum were read on MSD imager, and titers calculated using the parallel line method. Evaluations included dynamic range, assay reproducibility, and stability over time. We compared M9ELISA results to those from a pseudovirion-based neutralization assay in sera from a mixed cohort of unvaccinated and vaccinated individuals (n = ~116) and to competitive Luminex immunoassay (cLIA) results in sera from a predominantly unvaccinated cohort (n = 4426). The linear range of the assay extended over 5 logs, with inter-assay reproducibility coefficient of variation ≤25% for all types. The pre-coated plates were stable for at least 2 years. Spearman correlation of antibody titers showed excellent correlation with PBNA (r = 0.86-0.97) and moderate correlation (r = 0.52-0.68) with cLIA. Thus, the M9ELISA can serve as a useful platform for high-throughput, sensitive and simultaneous quantitation of the antibody responses to nine HPV vaccine types. |
Human papillomavirus oral-and sero-positivity in fanconi anemia
Sauter SL , Zhang X , Romick-Rosendale L , Wells SI , Myers KC , Brusadelli MG , Poff CB , Brown DR , Panicker G , Unger ER , Mehta PA , Bleesing J , Davies SM , Kovacic MB . Cancers (Basel) 2021 13 (6) 1-18 High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predis-position to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96–11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
A prospective cohort study of immunogenicity of quadrivalent human papillomavirus vaccination among Alaska Native Children, Alaska, United States
Bruce MG , Meites E , Bulkow L , Panicker G , Hurlburt D , Lecy D , Thompson G , Rudolph K , Unger ER , Hennessy T , Markowitz LE . Vaccine 2020 38 (42) 6585-6591 OBJECTIVE: In the United States, HPV vaccination is routinely recommended at age 11 or 12 years; the series can be started at age 9. We conducted a cohort study to assess long-term immunogenicity of quadrivalent HPV vaccine (4vHPV) in an American Indian/Alaska Native (AI/AN) Indigenous population. METHODS: During 2011-2014, we enrolled AI/AN girls and boys aged 9-14 years, who were vaccinated with a 3-dose series of 4vHPV. Serum specimens were collected at five time points: immediately prior to doses 2 and 3, and at one month, one year, and two years after series completion. Antibody testing was performed using a multiplex virus-like-particle-IgG ELISA for 4vHPV types (HPV 6/11/16/18). RESULTS: Among 477 children (405 girls/72 boys) completing the 3-dose series, median age at enrollment was 11.2 years. Of the 477, 72 (15%) were tested before dose 2 and 70 (15%) before dose 3. Following series completion, 435 (91%) were tested at one month, 382 (80%) at one year, and 351 (74%) at two years. All tested participants had detectable antibody to 4vHPV types at all time points measured. Geometric mean concentrations (GMCs) for 4vHPV types at one month and two years post-series completion were 269.9 and 32.7 AU/ml for HPV6, 349.3 and 42.9 AU/ml for HPV11, 1240.2 and 168.3 IU/ml HPV16, and 493.2 and 52.2 IU/ml for HPV18. Among children tested after each dose, GMCs after doses 1 and 2 were 3.9 and 32.2 AU/ml for HPV6, 5.3 and 45.6 AU/ml for HPV11, 20.8 and 187.9 IU/ml for HPV16; and 6.6 and 49.7 IU/ml for HPV18. No serious adverse events were reported. CONCLUSION: All AI/AN children developed antibodies to all 4vHPV types after vaccination. GMCs rose after each dose, then decreased to a plateau over the subsequent two years. This cohort will continue to be followed to determine duration of antibody response. |
Evaluation of serological assays to monitor antibody responses to single-dose HPV vaccines
Tsang SH , Basu P , Bender N , Herrero R , Kemp TJ , Kreimer AR , Muller M , Panicker G , Pawlita M , Pinto LA , Sampson JN , Sankaranarayanan R , Schussler J , Sehr P , Sierra MS , Unger ER , Waterboer T , Hildesheim A . Vaccine 2020 38 (38) 5997-6006 INTRODUCTION: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown. METHODS: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation, and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test. RESULTS: HPV-16: Seropositivity range was 97.1-99.5% for single dose and 98.8-99.8% overall. CV range was 4.0-18.0% for single dose and 2.9-19.5% overall. ICC range was 0.77-0.99 for single dose and 0.74-0.99 overall. Correlation with SEAP-NA range was 0.43-0.85 for single dose and 0.51-0.90 overall. Weighted-kappa range was 0.34-0.82 for single dose and 0.45-0.84 overall. HPV-18: Seropositivity range was 63.9-94.7% for single dose and 86.2-97.9% overall. CV range was 8.1-18.2% for single dose and 4.6-18.6% overall. ICC range was 0.75-0.99 for single dose and 0.83-0.99 overall. Correlation with SEAP-NA range was 0.31-0.99 for single dose and 0.27-0.96 overall. Weighted-kappa range was 0.35-0.83 for single dose and 0.45-0.84 overall. HPV-16 seronegativity was <5% for all assays. HPV-18 seronegativity range was 5.5-17.3%. For LIA-4 and GST-L1 where the proportion of seronegativity was >10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil. CONCLUSIONS: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination. |
Duration of cellular and humoral responses after quadrivalent human papillomavirus vaccination in healthy female adults with or without prior type 16 and/or 18 exposure
Lai L , Ault K , Rouphael N , Beck A , Domjahn B , Xu Y , Anderson EJ , Cheng A , Nakamura A , Hoagland RJ , Kelley C , Edupuganti S , Mask K , Nesin M , Unger ER , Panicker G , David H , Mulligan MJ . Vaccines (Basel) 2020 8 (3) Human papillomavirus virus (HPV) vaccines aim to provide durable protection and are ideal to study the association of cellular with humoral responses. We assessed the duration and characteristics of immune responses provided by the quadrivalent HPV (4vHPV) vaccine in healthy female adults with or without prior exposure with type 16 and 18 HPV. In a prospective cohort, vaccine naive females received three doses of 4vHPV vaccine and were followed for two years to assess cellular (intracellular cytokine staining, proliferation and B cell ELISpot assays) and humoral (multiplex L1/L2 viral-like particles (VLP) and M4 ELISAs) responses. Frequencies of vaccine-specific CD4+ T cells correlated with antibody responses. Higher HPV antibody titers were found at all time points in participants previously exposed to HPV, except for anti-HPV-18 at Day 187 (one week post the third vaccination). Retrospective cohorts enrolled females who had previously received two or three 4vHPV doses and tested antibody titers by M4 ELISA and pseudovirion neutralization assay along with memory B cells (MBCs). Almost all women enrolled in a retrospective cohort with two prior doses and all women enrolled in a retrospective cohort with three prior doses had sustained antibody and memory responses. Our findings indicate that HPV vaccination induces a long-lasting, robust cellular and humoral immune responses. |
Chlamydia trachomatis and human papillomavirus serostatus in Puerto Rican women
Castaneda-Avila MA , Suarez-Perez E , Bernabe-Dones R , Unger ER , Panicker G , Ortiz AP . P R Health Sci J 2020 39 (1) 28-33 OBJECTIVE: There is a high prevalence of human papillomavirus (HPV) infection in Puerto Rico, but little is known about the prevalence of Chlamydia trachomatis (CT) infection in healthy Puerto Rican women. Thus we aimed to evaluate the seroprevalence and association and the association between HPV and CT. METHODS: This was a secondary data analysis from a cross-sectional, populationbased, study of HPV infection in women aged 16-64 years in Puerto Rico (2010-2013). Enzyme-linked immunosorbent assays (ELISA) were used to detect serum antibodies to CT and HPV. Logistic regression models were used to estimate the odds ratio (OR) for the association between HPV and CT serostatus. RESULTS: The study included 524 women; mean age was 42 years. Overall, 97 (18.5%) women were CT-seropositive, 251 (47.0%) were HPV seropositive, and 57 (10.9%) had antibodies for both CT and HPV. Women who were CT-seropositive were more likely (p<0.05) to also be seropositive to any HPV type (ORadjusted: 1.7, IC 95% =1.1, 2.6), HPV 16/18 (ORadjusted: 1.6, IC 95% =1.0, 2.6) and HPV 6/11 (ORadjusted: 1.6, IC 95% =1.1, 2.6) than those CT-seronegative, after adjusting for possible confounding factors. CONCLUSION: Given the association between CT and HPV seropositivity, longitudinal studies to evaluate whether CT infection influences HPV incidence and persistence in this group are warranted. |
Comparison of a VLP-based and GST-L1-based multiplex immunoassay to detect vaccine-induced HPV-specific antibodies in first-void urine
Pattyn J , Panicker G , Willhauck-Fleckenstein M , Van Keer S , Teblick L , Pieters Z , Tjalma WAA , Matheeussen V , Van Damme P , Waterboer T , Unger ER , Vorsters A . J Med Virol 2020 92 (12) 3774-83 BACKGROUND: Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). METHODS: We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bi- or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs ). FINDINGS: As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine p = 0.0003; serum p </= 0.0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, p </= 0.001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, p </= 0.0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, p </= 0.0001). CONCLUSION: FV urine HPV antibody detection is comparable with both assays, further supporting this non-invasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection. This article is protected by copyright. All rights reserved. |
Delayed dosing intervals for quadrivalent human papillomavirus vaccine do not reduce antibody avidity
Brady AM , Walter EB , Markowitz LE , Unger ER , Panicker G . Hum Vaccin Immunother 2020 16 (8) 1-6 The quadrivalent HPV vaccine (4vHPV) was originally recommended as a three-dose series (0/2/6 months), though delays in completing the series frequently occur. We previously found delayed dosing in girls resulted in similar or higher antibody titers compared to on-time dosing. Archived sera from 262 healthy females aged 9-18 recruited from pediatric clinics were tested to determine if delayed dosing intervals affected antibody avidity. Avidity index (AI; ratio of IgG Ab bound in the treated and untreated sample) was determined pre- and post-dose 3 4vHPV for each participant using a modified multiplex ELISA. Data were grouped by dosing intervals: (1) on-time dose 2 and 3, (2) delayed dose 2 and on-time dose 3, (3) on-time dose 2 and delayed dose 3, (4) delayed dose 2 and 3. Overall, mean AI was highest for HPV16 and lowest for HPV6. As expected, AI did not differ between groups 1 & 3 or groups 2 & 4 pre-dose 3, however, for most types mean AI was significantly higher both pre- and post-dose 3 for groups with delayed dose 2. For all types, mean AI was higher post-dose 3 in all delayed dosing groups compared to group 1. One month post-dose 3, there was a positive but weak correlation between AIs and antibody titer for HPV 6 (rho = 0.25, p = .0001), HPV 11 (rho = 0.14, p = .0370), HPV 16 (rho = 0.11, p = .0934), and HPV 18 (rho = 0.37, p < .0001). Our findings suggest longer intervals between doses result in higher antibody avidity, providing further evidence that delayed dosing of 4vHPV does not hinder the immune response. |
Priming effect of bivalent and quadrivalent vaccine for HPV 31/33/45/52: an exploratory analysis from two clinical trials
Sauvageau C , Panicker G , Unger ER , De Serres G , Schiller J , Ouakki M , Gilca V . Hum Vaccin Immunother 2019 16 (3) 590-594 The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naive (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naive subjects. In study B, a dose of 9vHPV was administered 36-96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8-8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3-8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine. |
Transgender women have higher human papillomavirus prevalence than men who have sex with men - two U.S. cities, 2012-2014
Singh V , Gratzer B , Gorbach PM , Crosby RA , Panicker G , Steinau M , Amiling R , Unger ER , Markowitz LE , Meites E . Sex Transm Dis 2019 46 (10) 657-662 BACKGROUND: Human papillomavirus (HPV) prevalence is high among men who have sex with men (MSM), yet little is known about HPV among transgender women (TGW). We assessed HPV prevalence and knowledge among TGW compared with MSM. METHODS: We enrolled TGW and MSM aged 18 to 26 years from clinics in Chicago and Los Angeles during 2012 to 2014. Participants self-reported gender identity, HIV status, HPV knowledge, and vaccination status. Self-collected anal and oral specimens were tested for HPV DNA (37 types); serum was tested for HPV antibodies (4 vaccine types). Prevalence among unvaccinated TGW and MSM was compared using prevalence ratios (PRs) and 95% confidence intervals (CIs). Participants without DNA or serologic evidence of HPV were considered naive. RESULTS: Among 1033 participants, 49 were TGW. Among 44 TGW and 855 MSM who were unvaccinated, any HPV DNA was detected in anal specimens from 39 (88.6%) TGW and 606 (70.9%) MSM (PR, 1.3; 95% CI, 1.1-1.4), and oral specimens from 4 (9.1%) TGW and 81 (9.5%) MSM (PR, 1.0; 95% CI, 0.4-2.5). Antibodies were detected among 37 (84.1%) TGW and 467 (54.6%) MSM (PR, 1.5; 95% CI, 1.3-1.8). Most participants were naive to 1 or more HPV vaccine type/s, including 29 (65.9%) TGW and 775 (90.6%) MSM (PR, 0.7; 95% CI, 0.6-0.9). Most TGW (55.1%) had never heard of HPV vaccine. CONCLUSIONS: Among TGW, HPV prevalence was high and knowledge was low. Most were still naive to 1 or more HPV vaccine type. Although vaccination ideally occurs prior to exposure, findings support existing national recommendations to vaccinate TGW and MSM, and suggest additional outreach might increase vaccination. |
Long intervals between two doses of HPV vaccines and magnitude of the immune response: A post-hoc analysis of two clinical trials
Gilca V , Sauvageau C , Panicker G , De Serres G , Schiller J , Ouakki M , Unger ER . Hum Vaccin Immunother 2019 15 1980-1985 The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6- month or a 3-8 year interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9-10 year-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9-14 years received a dose of 9vHPV 3-8 years later (mean 5.4 years). In both studies blood samples were collected before and 1 month post-second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One-month post-second dose, the GMTs increased 40- to 91-fold for those with a 6-month interval between doses and 60- to 82-fold for those with a 3-8 year interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or of the Quebec Public Health Institute. |
Seroprevalence of human papillomavirus 6/11/16/18 among self-identified gay/bisexual men who have sex with men, men who have sex with women, and females, United States, 2003-2010
Lewis RM , Markowitz LE , Panicker G , Unger ER . Clin Infect Dis 2018 69 (6) 1011-1018 Background: Differences in human papillomavirus (HPV) seroprevalence by sex have been observed, likely due to differences in the anatomic site of HPV exposure. Seroconversion may be more likely after exposure at non-keratinized (mucosal) compared to keratinized epithelium. We compared seroprevalence among self-identified gay/bisexual men who have sex with men (MSM) and females, two groups more likely exposed at mucosal epithelium, and men who only have sex with women (MSW), a group likely exposed primarily at keratinized epithelium, using data from the National Health and Nutrition Examination Survey from 2003-2010. Methods: HPV 6/11/16/18 serum antibody was detected using a multiplexed, competitive luminex immunoassay. Weighted seroprevalence was estimated among unvaccinated, sexually experienced 18-59 year-old MSM, MSW, and females, overall and by demographic and sexual behavior characteristics. Seroprevalences were compared using prevalence ratios adjusted for sexual behavior (aPRs). Results: Overall, seroprevalence in MSM, MSW, and females was 42.6%, 13.2%, and 37.1%, respectively. Seroprevalence in MSM was comparable to females (aPR: 0.85, 95% CI: 0.68-1.08) and higher than MSW (aPR: 2.72, 95% CI: 2.19-3.38). MSW had a significantly lower seroprevalence than females (aPR: 0.31, 95% CI: 0.28-0.34). Similar associations were seen in all sociodemographic subgroups. Seroprevalence increased with number of lifetime sex partners in all groups. Conclusions: In this population-based survey, HPV seroprevalence among groups likely exposed at mucosal epithelium (MSM, females) was comparable; seroprevalence in both groups was higher than in MSW. Future research could explore whether differences in seropositivity following infection results in differential protection from future infection. |
Immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent and one dose of bivalent HPV vaccine versus two doses of nonavalent vaccine - A randomized clinical trial
Gilca V , Sauvageau C , Panicker G , De Serres G , Ouakki M , Unger ER . Vaccine 2018 36 (46) 7017-7024 BACKGROUND: Limited data is available on the use of different HPV vaccines in the same subjects. We evaluated the immunogenicity and safety of a mixed vaccination schedule with one dose of nonavalent (9vHPV) and one dose of bivalent vaccine (2vHPV) administered in different order versus two doses of 9vHPV vaccine. METHODS: 371 girls and boys aged 9-10years were randomized (1:1) to receive (I) two doses of 9vHPV or (II) a mixed schedule of 2vHPV+9vHPV or 9vHPV+2vHPV with a 6month interval. Antibodies to HPV were tested by ELISA in blood samples collected one or six months post-first dose and one month post-second dose. RESULTS: Post-first dose of 9vHPV 99.4-100% of subjects were seropositive to 9 HPV types included in the vaccine. GMTs varied from 5.0 to 73.6IU(AU)/ml depending on HPV type. Post-first dose of 2vHPV all subjects were seropositive to HPV16 and 18 (GMTs 16.7 and 11.7IU/ml, respectively) and 50.0-76.7% were seropositive to 7 types not included in 2vHPV (GMTs varied from 0.3 to 17.5AU/ml depending on type). Post-second dose all subjects, regardless of the study group, were seropositive to 9 HPV types included in 9vHPV. Anti-HPV16 and 18 GMTs were higher in subjects with the mixed schedule and for the other 7 HPV types higher in subjects who received two doses of 9vHPV vaccine. A higher proportion of subjects who received 2vHPV reported local or systemic adverse events than those who received 9vHPV as the first dose. Post-second dose there were no differences in reported adverse events between the two vaccines. CONCLUSIONS: The results show the mixed HPV vaccination schedules used in this study are immunogenic and have an acceptable safety profile. Although the seroprotective threshold of antibodies remains unknown the 100% seropositivity to all 9 HPV types included in 9vHPV and the increase of GMTs observed in all study groups post-second dose administration are reassuring and suggest protection might be achieved regardless of the schedule used. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT02567955. |
Antibody persistence after a single dose of quadrivalent HPV vaccine and the effect of a dose of nonavalent vaccine given 3-8 years later - an exploratory study
Gilca V , Sauvageau C , Panicker G , De Serres G , Ouakki M , Unger ER . Hum Vaccin Immunother 2018 15 (2) 1-5 The objective of this study was to assess the persistence of antibodies after a single dose of quadrivalent HPV vaccine (4vHPV) and the effect of a dose of nonavalent HPV vaccine (9vHPV) given 3-8 years later. Such data might be of interest in the decision-making process regarding the 2-dose course completion in non-compliant vaccinees in jurisdictions which switched from 4vHPV to 9vHPV. Girls who previously received a single dose of 4vHPV were eligible to participate. Blood specimens were collected just before and one month post-9vHPV administration. The specimens were tested by ELISA for the presence of antibodies to 9 HPV types included in the 9vHPV. Thirty-one girls aged 13-18 years (mean 15.5 years) participated in the study. Pre-9vHPV administration, all participants were seropositive to 4 HPV types included in 4vHPV and 58%-87% were seropositive to the five other HPV types included in the 9vHPV. GMTs were 6.1 AU/ml, 7.7 AU/ml, 20.1 IU/ml and 6.3 IU/ml to HPV6, HPV11, HPV16 and HPV18, respectively. The GMTs for the other five HPV types varied from 1.0 to 2.9 AU/ml. One month post-9vHPV administration all 31 participants were seropositive to all 9 HPV types with a 36.1 to 89.1-fold increase of GMTs. High seropositivity rates observed several years after a single dose of 4vHPV and 100% seropositivity after a dose of 9vHPV suggest that this schedule might be used in non-compliant vaccinees or when switching immunization programs from 4vHPV to 9vHPV. |
Seroprevalence of HPV 6, 11, 16 and 18 and correlates of exposure in unvaccinated women aged 16-64 years in Puerto Rico
Ortiz AP , Tortolero-Luna G , Romaguera J , Perez CM , Gonzalez D , Munoz C , Gonzalez L , Marrero E , Suarez E , Palesfky JM , Panicker G , Unger ER . Papillomavirus Res 2018 5 109-113 BACKGROUND: To understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area. METHODS: As part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16-64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR. RESULTS: 32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 - 29%, HPV11 - 18%, HPV16 - 23%, and HPV18 - 17%; seroprevalence was high in the youngest age-group (16-19: 26-37%). HPV seropositivity was associated with having >/= 3 lifetime sexual partners (OR=2.5, 95% CI=1.7-3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2-2.6). CONCLUSIONS: The high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16. |
Seroprevalence of human papillomavirus (HPV) Type 6, 11, 16, 18, by anatomic site of HPV infection, in women aged 16-64 years living in the metropolitan area of San Juan, Puerto Rico
Perez-Caraballo AM , Suarez E , Unger ER , Palefsky JM , Panicker G , Ortiz AP . P R Health Sci J 2018 37 (1) 26-31 OBJECTIVE: It is unknown if human papillomavirus (HPV) serum antibody responses vary by anatomic site of infection. We aimed to assess the seroprevalence for HPV 6, 11, 16 and 18 in association with HPV DNA detection in different anatomic sites among women. METHODS: This cross sectional population-based study analyzed data from 524 women aged 16-64 years living in the San Juan metropolitan area of Puerto Rico (PR). Questionnaires were used to assess demographic and lifestyle variables, while anogenital and blood samples were collected for HPV analysis. Logistic regression models were used to estimate the adjusted prevalence odds ratio (POR) in order to determine the association between HPV DNA infection status in the cervix and anus and serum antibody status, controlling for different potential confounders. RESULTS: Overall, 46.9% of women had detectable antibodies to one or more types whereas 8.7% had HPV DNA for one or more of these types detected in cervix (4.0%) or anus (6.5%). Women with cervical HPV detection tended to be more HPV seropositive than women without cervical detection (adjusted POR (95%CI): 2.41 (0.90, 6.47), p=0.078); however the type-specific association between cervical DNA and serum antibodies was only significant for HPV 18 (adjusted POR (95% CI): 5.9 (1.03, 33.98)). No significant association was detected between anal HPV and seropositivity (p>0.10). CONCLUSION: Differences in the anatomic site of infection could influence seroconversion, however, longitudinal studies will be required for further evaluation. This information will be instrumental in advancing knowledge of immune mechanisms involved in anatomic site response. |
Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals
Widdice LE , Unger ER , Panicker G , Hoagland R , Callahan ST , Jackson LA , Berry AA , Kotloff K , Frey SE , Harrison CJ , Pahud BA , Edwards KM , Mulligan MJ , Sudman J , Bernstein DI . Vaccine 2018 36 (6) 881-889 BACKGROUND: The originally recommended dosing schedule, 0, 2, 6months, for the 3-dose quadrivalent human papillomavirus vaccine (4vHPV) was often not followed, resulting in longer than recommended intervals between doses and interest in the effect of prolonged intervals. Recent two-dose recommendations require investigations into the effect of delaying dose 2. METHODS: This multi-site, prospective study enrolled healthy 9-17year old girls (n=1321) on the day of or within 28days following a third dose of 4vHPV vaccination. Antibody titers to 4vHPV types were measured at one and six months post-dose 3 from all participants and post-dose 2 from participants who were on time for dose 3. To compare antibody responses, participants were categorized into groups: second and third doses on time (control group); on-time dose 2, substantially late dose 3 (group 2); substantially late dose 2, on-time dose 3 (group 3); both doses substantially late (group 4). Analyses compared age-adjusted geometric mean titers (GMTs) at one-month and six-months post-dose 3, effect of delaying the second dose, and two versus three doses as well as post-dose 2 GMTs, stratified by age. RESULTS: Compared to on-time dosing, one-month post-dose 3 GMTs were non-inferior in groups 2, 3, and 4 and were superior in group 2. Six month post-dose 3 GMTs were superior in groups 2, 3, and 4 for each genotype, except HPV 18 in group 3. Age-adjusted post does 2 titers were significantly lower than post-dose 3 titers when dose 2 was on time but were significantly higher when dose 2 was substantially late. Participants >/=15years old had no difference in post-dose 2 titers compared to <15year olds when dose 2 was substantially delayed. CONCLUSIONS: Prolonged intervals between doses do not appear to diminish and may enhance antibody response to 4vHPV. ClinicalTrials.gov (NCT00524745). |
Serum immune profiling for early detection of cervical disease
Ewaisha R , Panicker G , Maranian P , Unger ER , Anderson KS . Theranostics 2017 7 (16) 3814-3823 Background: The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide. The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN. Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection. Methods: To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83). Results: Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, p<0.04). Of the E Abs, anti-E7 Abs were the most frequently detected (6.6%, 19.5%, and 30.3%, respectively). The least frequently detected Abs were E1 and E2-Abs in CIN 0/I (1.3%) and E1-Abs in CIN II/III (1.2%) and ICC (7.9%). HPV16-specific Abs correlated with HPV16 DNA detected in the cervix in 0% of CIN 0/I, 21.2% of CIN II/III, and 45.5% of ICC. A significant number (29 - 73%) of E4, E7, L1, and L2 Abs had cross-reactivity between HPV types. Conclusion: HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease. |
Antibody response to human papillomavirus vaccination and natural exposure in individuals with Fanconi Anemia
Mehta PA , Sauter S , Zhang X , Davies SM , Wells SI , Myers KC , Panicker G , Unger ER , Butsch Kovacic M . Vaccine 2017 35 6712-6719 Fanconi anemia (FA) is a rare genetic disorder associated with predisposition to head and neck and gynecological squamous cell cancers. In the general population, these cancers are commonly linked to human papillomavirus (HPV) infection. Antibodies to natural HPV infection and HPV vaccination were evaluated in 63 individuals with FA while considering host immune factors. Approximately 30% of reportedly unvaccinated participants were seropositive (HPV6-38%, HPV11-25%, HPV16-26%, and HPV18-26%). Seropositivity was significantly associated with having had sex regardless of age (p=.007). Most participants showed seropositivity after HPV vaccination (HPV6-100%, HPV11-100%, HPV16-100% and HPV18-92%). Interestingly, titers for all 4 subtypes were significantly lower in the post-hematopoietic stem cell transplant (HSCT) participants compared to those who received the vaccine, but had not undergone HSCT (HPV6-p=.030, HPV11-p=.003, HPV16-p=.018, HPV18-p=<.001). It is unclear if these titers sufficiently protect from new infection since protective serologic cut offs have not yet been defined for the HPV vaccine. Individual immune functions were not associated with HPV seropositivity, however, underlying heterogeneous immune deficiency may explain higher rates of seropositivity in our younger unvaccinated participants (age 4-13 years). To better measure the efficacy of HPV vaccination in those with FA and other immune-compromised or cancer-prone disorders, future well-controlled vaccine studies are required. |
Description of a novel multiplex avidity assay for evaluating HPV antibodies
Brady AM , Unger ER , Panicker G . J Immunol Methods 2017 447 31-36 Limited data exists regarding antibody avidity for human papillomavirus (HPV). We describe development of a multiplex electrochemiluminescent avidity ELISA for four HPV types (HPV 6, 11, 16, 18) by adding a dissociating step to our established multiplex HPV VLP ELISA. Initial experiments exploring ammonium thiocyanate, sodium thiocyanate and guanidine hydrochloride (GuHCl) as dissociating agents identified GuHCl as most promising. Dissociation conditions with GuHCl were varied (concentration, incubation time, temperature) to select conditions with minimal impact on VLP integrity as measured with monoclonal antibodies to conformational epitopes. Avidity index (AI) was calculated based on a standard curve as ratio of bound IgG in GuHCl treated versus untreated sample. To evaluate our assay we determined AI in sera with known HPV titers. We selected 32 residual anonymized sera from individuals with a wide range of titers for HPV6, 11, 16, and 18. AIs were similar across multiple dilutions of serum within the assay's dynamic range and were reproducible with two plate lots. This assay will aid in understanding HPV antibody avidity and maturation in response to natural infection and varying vaccine schedules. This is the first report of a VLP-based multiplexed avidity ELISA that evaluates assay parameters for all nine HPV vaccine types. |
Monitoring for Human Papillomavirus Vaccine Impact Among Gay, Bisexual, and Other Men Who Have Sex With Men-United States, 2012-2014
Meites E , Gorbach PM , Gratzer B , Panicker G , Steinau M , Collins T , Parrish A , Randel C , McGrath M , Carrasco S , Moore J , Zaidi A , Braxton J , Kerndt PR , Unger ER , Crosby RA , Markowitz LE . J Infect Dis 2016 BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are at high risk for HPV; vaccination is recommended for U.S. males, including MSM through age 26. We assessed evidence of HPV among vaccine-eligible MSM and transgender women to monitor vaccine impact. METHODS: During 2012-14, MSM age 18-26 at selected clinics completed a computer-assisted self-interview regarding sexual behavior, HIV status, and vaccinations. Self-collected anal swab and oral rinse specimens were tested for HPV DNA (37 types) by L1 consensus PCR; serum was tested for HPV antibodies (4 types) by multiplexed VLP-based IgG direct ELISA. RESULTS: Among 922 vaccine-eligible participants, mean age was 23, and mean number of lifetime sex partners was 37. Among 834 without HIV, any anal HPV was detected in 69.4% and any oral HPV in 8.4%, yet only 8.5% had evidence of exposure to all quadrivalent vaccine types. In multivariate analysis, HPV prevalence varied significantly (p<0.05) by HIV status, sexual orientation, and lifetime sex partners, but not race/ethnicity. DISCUSSION: Most young MSM lacked evidence of current or past infection with all vaccine-type HPV, suggesting they could benefit from vaccination. Vaccination impact among MSM may be assessed by monitoring HPV prevalence, including in self-collected specimens. |
Seroprevalence of 9 human papillomavirus types in the United States, 2005-2006
Liu G , Markowitz LE , Hariri S , Panicker G , Unger ER . J Infect Dis 2015 213 (2) 191-8 BACKGROUND: A 9-valent human papillomavirus (HPV) vaccine, licensed in 2014, prevents 4 HPV types targeted by the quadrivalent vaccine (6/11/16/18) and 5 additional high-risk (HR) types (31/33/45/52/58). Measuring seropositivity before vaccine introduction provides baseline data on exposure to types targeted by vaccines. METHODS: We determined seroprevalence of HPV 6/11/16/18/31/33/45/52/58 among 4943 persons aged 14-59 years who participated in the National Health and Nutrition Examination Survey, 2005-2006. RESULTS: Among females, seroprevalence was 40.5% for any of the 9 vaccine types, 30.0% for any 7 HR types (16/18/31/33/45/52/58), 18.3% for any 5 additional types (31/33/45/52/58), and 19.0% for 16/18. Compared with non-Hispanic whites, non-Hispanic blacks had higher seroprevalence of 31/33/45/52/58 (36.8% vs 15.9%) and 16/18 (30.1% vs 17.8%), while Mexican Americans had higher seroprevalence of 31/33/45/52/58 (23.6% vs 15.9%) (P < .05 for all). In multivariable analyses of data from females, race/ethnicity, number of sex partners, and age were associated with 16/18 and 31/33/45/52/58 seropositivity. Seropositivity was lower among males than among females (P < .001 for all type categories). CONCLUSIONS: In 2005-2006, about 40% of females and 20% of males had serological evidence of exposure to ≥1 of 9 HPV types. Seroprevalence of all type categories, especially HPV 31/33/45/52/58 among females, varied by race/ethnicity. |
Oral human papillomavirus is common in individuals with Fanconi anemia
Sauter SL , Wells SI , Zhang X , Hoskins EE , Davies SM , Myers KC , Mueller R , Panicker G , Unger ER , Sivaprasad U , Brown DR , Mehta PA , Butsch Kovacic M . Cancer Epidemiol Biomarkers Prev 2015 24 (5) 864-72 BACKGROUND: Fanconi Anemia (FA) is a rare genetic disorder resulting in a loss of function of the FA-related DNA repair pathway. Individuals with FA are predisposed to some cancers including oropharyngeal and gynecological cancers with known associations with human papillomavirus (HPV) in the general population. Since individuals with FA respond poorly to chemotherapy and radiation, prevention of cancer is critical. METHODS: To determine if individuals with FA are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with FA and 162 unaffected first-degree family members for 37 HPV types. RESULTS: Fourteen individuals (11.1%) with FA tested positive, significantly more (p=0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with FA (17.7% vs. 2.4% in family; p=0.003). HPV positivity also tended to be higher in the sexually inactive (8.7% in FA vs. 2.9% in siblings). Indeed, having FA increased HPV positivity 4.9 fold (95%CI: 1.6-15.4) considering age and sexual experience, but did not differ by other potential risk factors. CONCLUSION: Our studies suggest that oral HPV is more common in individuals with FA. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time. Impact HPV vaccination should be emphasized in those with FA as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine if the level of protection it offers in this population is adequate. |
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