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1.
BMC Infect Dis ; 20(1): 808, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153446

RESUMO

BACKGROUND: Although more than 10 years have passed since HPV vaccination was implemented, first as an interim programme (Emergent vaccine promotion programme) in November 2010, followed by incorporating into the National Immunization Programme in April, 2013 and suspended in June 2013, limited studies have investigated the HPV vaccine effectiveness against high-grade cervical lesions in Japan. METHODS: We collected the matched data of the results of cervical biopsy and history of vaccination from the Japan Cancer Society database. The subjects were women aged 20 to 29 years screened for cervical cancer between April, 2015 and March, 2017, and with information on HPV vaccination status. We estimated the relative risk of developing high-grade cervical lesions in vaccinated subjects using Poisson regression as compared to unvaccinated subjects. RESULTS: Among the 34,281 women screened, 3770 (11.0%) were vaccinated. The prevalence of CIN2+ was statistically significantly lower in the vaccinated women as compared to the unvaccinated women (Vaccine Effectiveness (VE) =76%; RR = 0.24, 95% CI:0.10-0.60). High VE against CIN3+ was also observed (91%; RR = 0.09, 95% CI:0.00-0.42). CONCLUSION: Women aged 20-29 years who received at least one dose of HPV vaccine had a significantly lower risk of high-grade cervical lesions than those not vaccinated. In Japan, HPV vaccination should be resumed in order to reduce the incidence of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Adulto , Neoplasia Intraepitelial Cervical/classificação , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Resultado do Tratamento , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/virologia , Adulto Jovem
2.
Anticancer Res ; 40(11): 5995-6002, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109537

RESUMO

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix.


Assuntos
Anticoncepcionais/efeitos adversos , Estrogênios/efeitos adversos , Progestinas/efeitos adversos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Feminino , Humanos , Papillomaviridae/fisiologia , Fatores de Risco , Neoplasias do Colo do Útero/virologia
3.
BMC Infect Dis ; 20(1): 801, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121447

RESUMO

BACKGROUND: According to the 2006 American Society for Colposcopy and Cervical Pathology guidelines, positive CIN2 p16 in women over the age of 25 should be managed with excisional treatment. However, excisional treatment is associated with physical, psychological and obstetric morbidity and can have a negative impact on sexual function. In our study we sought to identify a clear management strategy, addressing the impact of routine use of p16 immunohistochemistry in this population and identify appropriate criteria for patient selection with the aim of reducing over-treatment. METHOD: We studied the medical records of 130 patients who had undergone laser therapy for CIN2. Each patient underwent colposcopy, biopsy and HPV test and were tested for p16 protein,. Patients were divided based on HPV infection into: single infections, multiple infections. All patients underwent ZTA laser therapy with follow-up (2-year follow-up). STATISTICAL ANALYSIS: Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p < 0.05 were considered statistically significant. RESULTS: Single infections had a histological regression of 61.8% (21/34) and a histological persistence rate of 35.3% (12/34), which was greater than the multiple infection rate. The common characteristic that the women with persistence and progression had was the dimension of the lesion and the genotype 16. Ten cases of histological persistence and the only case of progression had one lesion greater than three quarters of the cervix. CONCLUSIONS: With the progress of our understanding of the natural history of infection from human papillomavirus and the increasing use of colposcopy, thanks to the addition of HPV genotyping and the technique of immunohistochemistry, conservative management of these lesions is now possible.


Assuntos
Neoplasia Intraepitelial Cervical/complicações , Neoplasia Intraepitelial Cervical/terapia , Tratamento Conservador/métodos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Progressão da Doença , Feminino , Seguimentos , Genótipo , Humanos , Imuno-Histoquímica , Terapia a Laser , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/virologia
4.
Zhonghua Fu Chan Ke Za Zhi ; 55(10): 708-715, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33120484

RESUMO

Objective: Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening. Methods: Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated. Results: (1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ+ of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ+ was higher than those of Cobas-HPV and SEQ-HPV (P<0.01). The sensitivity for CIN Ⅲ+ of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ+ of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ+ or CIN Ⅲ+ in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV (P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ+ and CIN Ⅲ+ (P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions: BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/análise , DNA Viral/genética , Detecção Precoce de Câncer , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Programas de Rastreamento/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos
5.
Medicine (Baltimore) ; 99(38): e22320, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957398

RESUMO

Cervical cancer is a serious global health problem. The objective of this study was to provide a suitable cytology-based cervical screening method in women of different ages in primary hospitals.This study was a retrospective cohort study that included 9765 women who underwent primary cytology-based cervical screening and were grouped by age (35-44, 45-54, and 55-64 years old). Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Furthermore, patients with positive outcomes of the 2 indices underwent cervical tissue biopsy. The positive rate of TCT and HPV was compared among the 3 defined age groups. The sensitivity, specificity, and positive predictive value of TCT and HPV were assessed.In total, 2.5% (241/9765) of women had atypical squamous cells of undetermined significance or worse by TCT. High-risk (HR)-HPV infection was found in 70 triage participants. Neoplastic changes were confirmed in 95 patients (95/437, 21.7%) by biopsies. Among the different age groups, the positive rate of abnormal cytology was significantly different (P = .003), and the positive rate of HR-HPV was similar (P = .299). The sensitivity of initial TCT testing to detect intraepithelial neoplasia was higher than that of triage HPV testing, whereas the specificity, the positive predictive value of triage HPV testing was higher than that of TCT. The Youden index of HPV testing was higher than that of TCT detection in the 3 age groups, namely 0.582 versus 0.432, 0.553 versus 0.228, and 0.416 versus 0.332, respectively.The results of this study indicate that TCT testing is suitable as a cervical cancer screening method for women ≥35 years old in primary hospitals. Triage testing for women with HR-HPV has a high negative predictive value, reduces the rate of misdiagnosis, seems to be an excellent triage method for repeat atypical squamous cells of undetermined significance, and reduces the number of referral colposcopies preventing unnecessary overtreatment. The results of this study provide a crucial foundation for a unified guideline cervical cancer screening for primary health care institutions.


Assuntos
Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Distribuição por Idade , China , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/virologia
6.
Medicine (Baltimore) ; 99(37): e22072, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925744

RESUMO

INTRODUCTION: Evidence has consistently shown the high efficacy of human papillomavirus (HPV) vaccines in preventing cervical cancers. However, the HPV vaccine uptake rate in Hong Kong is very low. We will develop and evaluate an innovative, theory-based multidisciplinary team-led school-based HPV vaccination health-promotion program (MDL-SHPVP), engaging female adolescents, parents/guardians, and secondary school personnel in multicomponent educational strategies and interactive discussions. METHODS AND ANALYSIS: A cluster randomized controlled trial is proposed. We will recruit 2520 female adolescents and their parents/guardians from 18 secondary day schools. The MDL-SHPVP is underpinned by the Health Belief Model and Precaution Adoption Process Model. Multicomponent interventions will be offered, including education sessions with small group dialogues with a registered nurse and trained healthcare and lay volunteers, and educational computer games. A team of volunteers will be established to raise HPV, cervical cancer, and HPV vaccine awareness. Outcomes include adolescents' uptake of the HPV vaccine, adolescents' intention to receive HPV vaccination, vaccine acceptance among parents/guardians, and parents'/guardians' and adolescents' HPV knowledge, attitudes, and beliefs. Data will be collected at baseline, 1 month, and 1 year after intervention. The generalized estimating equations analysis will be used for comparing the outcomes between the 2 groups. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (Ref. no.: 2019.055). We will disseminate the study findings via peer-reviewed publications and presentations at relevant events and international and local conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04438291.


Assuntos
Informação de Saúde ao Consumidor/organização & administração , Vacinas contra Papillomavirus , Aceitação pelo Paciente de Cuidados de Saúde , Serviços de Saúde Escolar/organização & administração , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pais/psicologia , Fatores Socioeconômicos , Estudantes/psicologia , Neoplasias do Colo do Útero/virologia
7.
BMC Infect Dis ; 20(1): 642, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873233

RESUMO

BACKGROUND: Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). METHODS: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. RESULTS: Among 310,545 female, 6067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p < 0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53). CONCLUSIONS: Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Coinfecção/complicações , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/complicações , Vaginite por Trichomonas/complicações , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Coinfecção/diagnóstico , Colposcopia , Estudos Transversais , Citodiagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/parasitologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
8.
PLoS Pathog ; 16(9): e1008827, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886721

RESUMO

Global burden of cervical cancer, the most common cause of mortality caused by human papillomavirus (HPV), is expected to increase during the next decade, mainly because current alternatives for HPV vaccination and cervical cancer screening programs are costly to be established in low-and-middle income countries. Recently, we described the development of the broadly protective, thermostable vaccine antigen Trx-8mer-OVX313 based on the insertion of eight different minor capsid protein L2 neutralization epitopes into a thioredoxin scaffold from the hyperthermophilic archaeon Pyrococcus furiosus and conversion of the resulting antigen into a nanoparticle format (median radius ~9 nm) upon fusion with the heptamerizing OVX313 module. Here we evaluated whether the engineered thioredoxin scaffold, in addition to humoral immune responses, can induce CD8+ T-cell responses upon incorporation of MHC-I-restricted epitopes. By systematically examining the contribution of individual antigen modules, we demonstrated that B-cell and T-cell epitopes can be combined into a single antigen construct without compromising either immunogenicity. While CD8+ T-cell epitopes had no influence on B-cell responses, the L2 polytope (8mer) and OVX313-mediated heptamerization of the final antigen significantly increased CD8+ T-cell responses. In a proof-of-concept experiment, we found that vaccinated mice remained tumor-free even after two consecutive tumor challenges, while unvaccinated mice developed tumors. A cost-effective, broadly protective vaccine with both prophylactic and therapeutic properties represents a promising option to overcome the challenges associated with prevention and treatment of HPV-caused diseases.


Assuntos
Antígenos de Neoplasias , Antígenos Virais , Proteínas Arqueais , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer , Imunidade Celular/efeitos dos fármacos , Nanopartículas , Papillomaviridae , Vacinas contra Papillomavirus , Pyrococcus furiosus/química , Tiorredoxinas , Neoplasias do Colo do Útero/imunologia , Animais , Antígenos de Neoplasias/química , Antígenos de Neoplasias/farmacologia , Antígenos Virais/química , Antígenos Virais/farmacologia , Proteínas Arqueais/química , Proteínas Arqueais/farmacologia , Linfócitos T CD8-Positivos/patologia , Vacinas Anticâncer/química , Vacinas Anticâncer/farmacologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/farmacologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Papillomaviridae/química , Papillomaviridae/imunologia , Vacinas contra Papillomavirus/química , Vacinas contra Papillomavirus/farmacologia , Tiorredoxinas/química , Tiorredoxinas/farmacologia , Neoplasias do Colo do Útero/virologia
9.
PLoS One ; 15(9): e0239611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997696

RESUMO

BACKGROUND: Sweden revised their cervical cancer screening program in 2017 to include cytology-based screening for women aged 23-29 years and primary human papillomavirus (HPV) testing for women aged 30-64 years; however, alternative strategies may be preferred. To inform cervical cancer prevention policies for unvaccinated women, we evaluated the cost-effectiveness of alternative screening strategies, including the current Swedish guidelines. METHODS: We adapted a mathematical simulation model of HPV and cervical cancer to the Swedish context using primary epidemiologic data. We compared the cost-effectiveness of alternative screening strategies that varied by the age to start screening, the age to switch from cytology to HPV testing, HPV strategies not preceded by cytology, screening frequency, and management of HPV-positive/cytology-negative women. RESULTS: We found that the current Swedish guidelines were more costly and less effective than alternative primary HPV-based strategies. All cost-efficient strategies involved primary HPV testing not preceded by cytology for younger women. Given a cost-effectiveness threshold of €85,619 per quality-adjusted life year gained, the optimal strategy involved 5-yearly primary HPV-based screening for women aged 23-50 years and 10-yearly HPV-based screening for women older than age 50 years. CONCLUSIONS: Primary screening based on HPV alone may be considered for unvaccinated women for those countries with similar HPV burdens.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Testes de DNA para Papilomavírus Humano/economia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer/normas , Feminino , Testes de DNA para Papilomavírus Humano/normas , Humanos , Sensibilidade e Especificidade , Suécia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/estatística & dados numéricos
10.
BMC Infect Dis ; 20(1): 629, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842982

RESUMO

BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.


Assuntos
Biodiversidade , Neoplasia Intraepitelial Cervical/epidemiologia , Progressão da Doença , Microbiota/genética , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Vagina/microbiologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactobacillus/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , RNA Ribossômico 16S/genética , Neoplasias do Colo do Útero/virologia
11.
PLoS One ; 15(8): e0237745, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817627

RESUMO

BACKGROUND: Cervical cancer is the second most common female reproductive cancer after breast cancer with 84% of the cases in developing countries. A high uptake of human papilloma virus (HPV) vaccination and screening, and early diagnosis leads to a reduction of incidence and mortality rates. Yet uptake of screening is low in Sub-Saharan Africa and there is an increasing number of women presenting for treatment with advanced disease. Nine women in their twenties die from cervical cancer in Kenya every day. This paper presents the biopsychosocial risk factors that impact on cervical cancer knowledge among Kenyan women aged 15 to 24 years. The findings will highlight opportunities for early interventions to prevent the worrying prediction of an exponential increase by 50% of cervical cancer incidences in the younger age group by 2034. METHODS: Data from the 2014 Kenya Demographic and Health Survey (KDHS) was analysed using complex sample logistic regression to assess biopsychosocial risk factors of knowledge of cervical cancer among young women aged 15 to 24 years (n = 5398). FINDINGS: Close to one third of the participants were unaware of cervical cancer with no difference between participants aged 15-19 years (n = 2716) and those aged 20-24 years (n = 2691) (OR = 1; CI = 0.69-1.45). Social predisposing factors, such as lack of education; poverty; living further from a health facility; or never having taken a human immunodeficiency virus (HIV) test, were significantly associated with lack of awareness of cervical cancer (p<0.001). Young women who did not know where to obtain condoms had an OR of 2.12 (CI 1.72-2.61) for being unaware of cervical cancer. Psychological risk factors, such as low self-efficacy about seeking medical help, and an inability to refuse unsafe sex with husband or partner, perpetuated the low level of awareness about cervical cancer (p<0.001). CONCLUSIONS: A considerable proportion of young women in Kenya are unaware of cervical cancer which is associated with a variety of social and psychological factors. We argue that the high prevalence of cervical cancer and poor screening rates will continue to prevail among older women if issues that affect young women's awareness of cervical cancer are not addressed. Given that the Kenyan youth are exposed to HPV due to early sexual encounters and a high prevalence of HIV, targeted interventions are urgently needed to increase the uptake of HPV vaccination and screening.


Assuntos
Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/psicologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/psicologia , Adolescente , Adulto , Detecção Precoce de Câncer , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Quênia/epidemiologia , Modelos Logísticos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Autoeficácia , Parceiros Sexuais , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Esfregaço Vaginal , Adulto Jovem
12.
Arch Virol ; 165(11): 2633-2640, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32812092

RESUMO

Our aim was to analyze the prevalence of high-risk human papillomavirus (HR-HPV) and its association with risk factors related to cervical lesions. We used 362 cervical samples from a transversal study to detect nineteen types from the high-risk HPV clade by highly sensitive PCR. Unexpectedly, we found a very high prevalence of HPV type 66 (32.8%), particularly in low-grade squamous intraepithelial lesions. A significant association of HPV66 with previously sexually transmitted disease was observed (p < 0.05). Our results strongly suggest that HPV66 might be indicative of cervical lesions that will not progress to cancer. HPV genotyping by methods that grouped type 66 with other HR-HPV clade types should be interpreted with caution.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/patologia , Detecção Precoce de Câncer , Feminino , Genótipo , Técnicas de Genotipagem , Humanos , Modelos Logísticos , México/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/classificação , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
13.
PLoS One ; 15(8): e0237988, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853216

RESUMO

OBJECTIVE: To evaluate the 9-year incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cumulative adherence to perform a next test in a cohort of women aged 40+ years with no cervical screening cytology within a window of 5 years (underscreened women), after baseline cervical cytology and HPV tests. METHODS: In Catalonia, Spain, co-testing with cytology and HPV test has been recommended in the Public Health system since 2006 for underscreened women. In 2007, 1,594 women with underscreened criteria were identified and followed through medical records form Pathological Department. 9-year cumulative incidence of histologically confirmed CIN2+ and cumulative adherence to perform a next test were estimated using Kaplan-Meier statistics. RESULTS: Follow-up was available for 1,009 women (63.3%) resulting in 23 women with. CIN2+ (2.3%). Of them, 4 women (17%) had both tests negative at baseline (3CIN2 and 1CIN3) with cumulative incidence of CIN2+ of 0.4% (95% CI: 0.1-1.4) at 5-years and 1.3% (95% CI: 0.4-3.7) at 9-years. During the first year, the prevalence among women with both tests positive was 27.0% (95% CI: 13.0-50.6) for CIN2+. Lost to follow-up was higher among women with both tests negative compared to those with both positive tests (38.7% vs 4.2%, p-value <0.001). 40.5% of the women HPV-/cyto- had a re-screening test during the 4 years following the baseline, increasing until 53.5% during the 6 years of follow-up. CONCLUSIONS: HPV detection shows a high longitudinal predictive value at 9-year to identify women at risk to develop CIN2+. The data validate a safe extension of the 3-year screening intervals (current screening interval) to 5-year intervals in underscreened women that had negative HPV result at baseline. It is necessary to establish mechanisms to ensure screening participation and adequate follow-up for these women.


Assuntos
Programas de Rastreamento , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Idoso , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Risco , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia
14.
Nat Genet ; 52(8): 800-810, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747824

RESUMO

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV+) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV+, and performed extended mutation analysis on an additional 89 tumors. We detected human papillomavirus (HPV)-clade-specific differences in tumor DNA methylation, promoter- and enhancer-associated histone marks, gene expression and pathway dysregulation. Changes in histone modification at HPV integration events were correlated with upregulation of nearby genes and endogenous retroviruses.


Assuntos
Epigenoma/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Transcriptoma/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Metilação de DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Uganda , Regulação para Cima/genética
15.
Medicine (Baltimore) ; 99(27): e21005, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629719

RESUMO

INTRODUCTION: Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. PATIENT CONCERNS: Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. DIAGNOSIS: The diagnosis was based on identification of HPV types and abnormal cytological findings. INTERVENTIONS: The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. OUTCOMES: All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. CONCLUSION: This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.


Assuntos
Neoplasia Intraepitelial Cervical/terapia , Hipertermia Induzida/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia
16.
Arch Virol ; 165(10): 2241-2247, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681408

RESUMO

Cervical cancer is primarily caused by persistent infection with high-risk human papillomavirus (HPV), and 70% of cases are associated with HPV16 and 18 infections. The objective of this study was to establish rapid, simple, and sensitive internally controlled recombinase-aided amplification (IC-RAA) assays for the detection of HPV16 and 18. The assays were performed at 39 ℃ and were completed within 30 min. A total of 277 clinical samples of exfoliated cervical cells were tested by IC-RAA assays and commercial HPV real-time fluorescent PCR kits using extracted DNA and samples treated with nucleic acid releasing agent. The analytical sensitivity of the IC-RAA assay was found to be 10 copies/µL for the detection of HPV16 and 18 when using recombinant plasmids as targets. The optimal concentration of the internal control (IC) plasmid and 18 was 1000 copies/µL for HPV16 and 100 copies/µL for HPV18. The clinical sensitivity of the IC-RAA assays for HPV16 using extracted DNA and samples treated with nucleic acid releasing agent was 98.73% and 97.47%, respectively, with kappa values of 0.977 (P < 0.01) and 0.955 (P < 0.01), respectively, and 100% The specificity in both cases. For HPV18, the sensitivity and specificity were 100%, and the kappa value was 1 for both samples (P < 0.01). The IC-RAA assay is a promising tool for the detection of HPV16 and HPV18, especially in resource-constrained settings.


Assuntos
DNA Viral/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Técnicas de Amplificação de Ácido Nucleico , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Colo do Útero/patologia , Colo do Útero/virologia , Primers do DNA/síntese química , Primers do DNA/genética , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/classificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
17.
PLoS One ; 15(7): e0235264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658921

RESUMO

OBJECTIVE: To identify health systems-level barriers to treatment for women who screened positive for high-risk human papillomavirus (hrHPV) in a cervical cancer prevention program in Kenya. METHODS: In a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya in 2018-2019, women underwent hrHPV testing offered through community health campaigns, and women who tested positive were referred to government health facilities for cryotherapy. The current analysis draws on treatment data from this trial, as well as two observational studies that were conducted: 1) periodic assessments of the treatment sites to ascertain availability of resources for treatment and 2) surveys with treatment providers to elicit their views on barriers to care. Bivariate analyses were performed for the site assessment data, and the provider survey data were analyzed descriptively. RESULTS: Seventeen site assessments were performed across three treatment sites. All three sites reported instances of supply stockouts, two sites reported treatment delays due to lack of supplies, and two sites reported treatment delays due to provider factors. Of the 16 providers surveyed, ten (67%) perceived lack of knowledge of HPV and cervical cancer as the main barrier in women's decision to get treated, and seven (47%) perceived financial barriers for transportation and childcare as the main barrier to accessing treatment. Eight (50%) endorsed that providing treatment free of cost was the greatest facilitator of treatment. CONCLUSION: Patient education and financial support to reach treatment are potential areas for intervention to increase rates of hrHPV+ women presenting for treatment. It is also essential to eliminate barriers that prevent treatment of women who present, including ensuring adequate supplies and staff for treatment.


Assuntos
Crioterapia/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/terapia , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde Comunitária/estatística & dados numéricos , Crioterapia/economia , Detecção Precoce de Câncer/economia , Feminino , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/organização & administração , Alocação de Recursos para a Atenção à Saúde/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Implementação de Plano de Saúde/economia , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/estatística & dados numéricos , Promoção da Saúde/economia , Promoção da Saúde/organização & administração , Promoção da Saúde/estatística & dados numéricos , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/organização & administração , Acesso aos Serviços de Saúde/estatística & dados numéricos , Mão de Obra em Saúde/organização & administração , Mão de Obra em Saúde/estatística & dados numéricos , Humanos , Quênia/epidemiologia , Programas de Rastreamento/economia , Programas de Rastreamento/organização & administração , Estudos Observacionais como Assunto , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Educação de Pacientes como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , População Rural/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
18.
Life Sci ; 256: 118026, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615187

RESUMO

AIM: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Genes MHC da Classe II/genética , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Regulação para Baixo , Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Transcriptoma , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
19.
BMC Womens Health ; 20(1): 139, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615963

RESUMO

BACKGROUND: Although human papillomavirus (HPV) infection has been regarded as the cause of cervical cancer in over 99% of cases, only a small fraction of HPV-infected women develop this malignancy. Emerging evidence suggests that alterations of mitochondrial DNA copy number (mtCN) may contribute to carcinogenesis. However, the relationship between mtCN and cervical cancer remains undetermined. METHODS: The current study included 591 cervical cancer cases and 373 cancer-free controls, all of whom were infected with high-risk HPV. Relative mtCN in cervical cancer exfoliated cells was measured by qRT-PCR assays, and logistic regression analysis was performed to compute odds ratios (ORs) and 95% confidence intervals (CIs). Interaction between mtCN and HPV types was assessed by using the Wald test in logistic regression models. RESULTS: HPV16, 18, 52, and 58 were the most common types in both case and control groups. Median mtCN in cases was significantly higher than that in controls (1.63 vs. 1.23, P = 0.03). After adjustment for age and HPV types, the highest quartile of mtCN was associated with increased odds of having cervical cancer (OR = 1.77, 95% CI = 1.19, 2.62; P < 0.01), as compared to the lowest quartile. A dose-response effect of mtCN on cervical cancer was also observed (Ptrend < 0.001). The interaction between mtCN and HPV types was statistically nonsignificant. CONCLUSIONS: In women who test HPV positive, the increase of mtCN in cervical exfoliated cells is associated with cervical cancer. This suggests a potential role of mtCN in cervical carcinogenesis.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/epidemiologia , China/epidemiologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
20.
Ann Epidemiol ; 49: 36-41, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711054

RESUMO

PURPOSE: This study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. METHODS: This cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991-1993 and in 1993-1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. RESULTS: We found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64-1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82-1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63-1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71-1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56-1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11-0.95). CONCLUSIONS: Overweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.


Assuntos
Índice de Massa Corporal , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Programas de Rastreamento , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Vigilância da População , Magreza/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia
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