scholarly journals Immunogenicity of a Two-Dose Human Papillomavirus Vaccine Schedule in HIV-Infected Adolescents with Immune Reconstitution

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 118
Author(s):  
Supattra Rungmaitree ◽  
Charin Thepthai ◽  
Zheng Quan Toh ◽  
Noppasit Musiwiraphat ◽  
Alan Maleesatharn ◽  
...  

HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9–15 years who had CD4 cell counts > 500 cells/mm3 and HIV-1 RNA < 40 copies/mL for at least one year were assigned to the 2D schedule, while older participants or those without IR received a three-dose (3D) schedule. Antibodies to HPV-16 and -18 were measured using a pseudovirion-based neutralization assay. A total of 96 subjects were enrolled; 31.3% and 68.7% received the 2D and 3D schedule, respectively. Of these, 66.7% and 57.6% of the 2D and 3D participants, respectively, were male. The seroconversion rates for HPV-16 and HPV-18 were 100% in all cases, except for HPV-18 in males who received the 3D schedule (97.4%). In males, the anti-HPV-16 geometric mean titers (GMTs) were 6859.3 (95% confidence interval, 4394.3–10,707.1) and 7011.1 (4648.8–10,573.9) in the 2D and 3D groups (p = 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2–2903.8) and 2859.8 (1810.0–4518.4) in the 2D and 3D (p = 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0–28,003.4) and 26,241.6 (16,972.7–40,572.3) in the 2D and 3D groups (p = 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8–11,780.6) and 9993.1 (5950.8–16,781.1) in the 2D and 3D groups (p = 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR.

2012 ◽  
Vol 7 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Baudelio Gutierrez ◽  
Anthony Leung ◽  
Kevin Trimell Jones ◽  
Peter Smith ◽  
Randee Silverman ◽  
...  

The human papillomavirus (HPV) vaccine was recently approved for use in males. Certain groups, such as men who have sex with men (MSM), are at increased risk of HPV infection. The purpose of the study was to understand perceptions of HPV and the vaccine among adolescent and young adult males, both heterosexual and MSM. Seventy-six males (45 heterosexual, 31 MSM) completed a questionnaire and participated in a focus group. Overall, 42% had heard of HPV and 39% had heard of the HPV vaccine. Males had moderate to favorable attitudes toward vaccination, although intentions to vaccinate were more neutral. MSM were more knowledgeable, aware, and in control of the decision to vaccinate than heterosexual males. Increasing awareness and knowledge about HPV and the vaccine may be necessary to encourage vaccination; certain subgroups of males may be more receptive to HPV vaccination than others.


Author(s):  
W Katherine Yih ◽  
Martin Kulldorff ◽  
Inna Dashevsky ◽  
Judith C Maro

Abstract Surveys of parents indicate safety is their top concern about human papillomavirus (HPV) vaccination. A data-mining method not requiring pre-specification of health outcome(s) of interest or post-exposure period(s) of potentially increased risk can check for associations between an exposure and any of thousands of medically attended health outcomes. The method was applied to the 9-valent HPV vaccine (HPV9) to detect potential safety problems. Data on 9-26-year-olds who had received HPV9 vaccine between November 4, 2016 and August 5, 2018, inclusive, were extracted from Marketscan and analyzed for statistically significant clustering of incident diagnoses within the hierarchy of ICD-10-CM coded diagnoses and temporally within the 1 year after vaccination, using the self-controlled tree-temporal scan statistic and TreeScan software. Only 56 days of post-vaccination enrollment was required; subsequent follow-up was censored at disenrollment. Multiple testing was adjusted for. The analysis included 493,089 doses of HPV9. Almost all signals resulted from temporal confounding, not unexpected with a 1-year follow-up period. The only plausible signals were for non-specific adverse events (e.g., injection-site reactions and headache) on Days 1-2 after vaccination, with attributable risks as low as 1 per 100,000 vaccinees. Considering the broad scope of the evaluation and the high statistical power, the findings of no specific serious adverse events should provide reassurance about this vaccine’s safety.


2019 ◽  
Vol 71 (4) ◽  
pp. 1022-1029 ◽  
Author(s):  
Robine Donken ◽  
Simon R M Dobson ◽  
Kim D Marty ◽  
Darrel Cook ◽  
Chantal Sauvageau ◽  
...  

Abstract Background Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. Methods Girls aged 9–13 years were randomized to receive 2D or 3D and were compared with women aged 16–26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. Results At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%–77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. Conclusions GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.


2019 ◽  
Vol 189 (4) ◽  
pp. 265-276
Author(s):  
Michelle L Johnson Jones ◽  
Julia Warner Gargano ◽  
Melissa Powell ◽  
Ina U Park ◽  
Linda M Niccolai ◽  
...  

Abstract Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2–3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008–2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received ≥24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18–positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.


2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 18s-19s
Author(s):  
Mu Mu Shwe ◽  
Kyi Kyi Nyunt ◽  
Khin Saw Aye ◽  
Hlaing Myat Thu ◽  
Hla Myat Mo Mo ◽  
...  

Abstract 11 In Myanmar, cervical cancer ranks as the first most frequent cancer among women aged between 15 to 44 years and Human Papillomavirus (HPV) vaccination program is not established yet. Information on HPV genotypes distribution in cervical cancer is crucial to predict the future impact of HPV vaccines. This study aimed to determine the HPV-DNA and genotypes among women with cervical pre-cancer and cancer in Myanmar. A cross-sectional descriptive study was performed in 169 women with cervical neoplasia during 2012 to 2014. After obtaining informed consent, cervical cells were collected from 134 women with cervical intraepithelial neoplasia (CIN) and 35 with squamous cell carcinoma (SCC) of the cervix attending Sanpya General Hospital, Yangon, and Central Women Hospital, Mandalay. HPV-DNA testing and genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). HR-HPV was identified in CINI (39.3%), CINII (58.6%), CINIII (66.7%), and SCC (77.1%). Overall, the most common genotypes were HPV-16 (68.1%), followed by HPV-31 (16.5%), HPV-18 (7.7%), HPV-58 (6.6%), and HPV-35 (1.1%). Among SCC, HPV-16 was the most common genotype (66.7%) followed by HPV-18 (14.8%), HPV-31 (11.1%), HPV-35 (3.7%), and HPV-58 (3.7%). In CINI, the most common genotype were HPV-16 (69.7%) followed by HPV-31 (21.2%), HPV-18 (6.1%) and HPV-58 (3.0%). In CINII, HPV-16 was most commonly determined (52.9%) followed by HPV-31 (23.5%), HPV-58 (17.6%), and HPV-18 (5.9%). In CINIII, HPV-16 was also the most common genotype (85.7%) followed by HPV-31 (7.1%) and HPV-58 (7.1%). Vaccine preventable genotype, HPV-16 was the most common genotype in Myanmar. This study highlighted that the establishment of National HPV vaccination program is needed to reduce the incidence and mortality of cervical cancer in Myanmar.[Table: see text][Table: see text] AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.


2001 ◽  
Vol 19 (7) ◽  
pp. 1906-1915 ◽  
Author(s):  
Stephen M. Schwartz ◽  
Janet R. Daling ◽  
Katherine A. Shera ◽  
Margaret M. Madeleine ◽  
Barbara McKnight ◽  
...  

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma.PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer–specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models.RESULTS: Eighty-six patients had HPV 18–related tumors and 210 patients had HPV 16–related tumors. Cumulative TM among patients with HPV 18–related tumors and among patients with HPV 16–related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16–related cancers, patients with HPV 18–related cancers were at increased risk for TM (HRTM, 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HRCCSM, 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HRTM, 3.1; 95% CI, 2.3 to 4.2; and HRCCSM, 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219).CONCLUSION: HPV 18–related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.


2006 ◽  
Vol 16 (3) ◽  
pp. 1048-1054 ◽  
Author(s):  
R. K. Singh ◽  
S. Maulik ◽  
S. Mitra ◽  
R. K. Mondal ◽  
P. S. Basu ◽  
...  

To understand the role of human papillomavirus (HPV) in recurrence of uterine cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18, 14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV-positive exfoliated cells (positive predictive value, 100%; negative predictive value, 27%) with concordance in HPV types. The recurrence of the disease was significantly associated with the presence of HPV in the exfoliated cell (P = 0.01) and plasma (P = 0.007) as well as high viral load in the exfoliated cell (P = 0.0002). Kaplan–Meier disease-free estimates have also shown the significant association between HPV prevalence in plasma and recurrence of the disease (P = 0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high viral load in the exfoliated cell as well as HPV presence in the plasma samples could be used in early detection of the patients at increased risk for disease recurrence and progression.


Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.


2017 ◽  
Vol 5 (3) ◽  
pp. 69-82 ◽  
Author(s):  
Sigrun Smola ◽  
Connie Trimble ◽  
Peter L. Stern

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.


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