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1.
Lancet ; 394(10197): 497-509, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31255301

RESUMO

BACKGROUND: More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination. METHODS: In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks. FINDINGS: We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+. After 5-8 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0·17, 95% CI 0·11-0·25) among girls aged 13-19 years, and decreased significantly by 66% (RR 0·34, 95% CI 0·23-0·49) among women aged 20-24 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0·46, 95% CI 0·33-0·66) among girls aged 13-19 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0·33, 95% CI 0·24-0·46) among girls aged 15-19 years, decreased significantly by 54% (RR 0·46, 95% CI 0.36-0.60) among women aged 20-24 years, and decreased significantly by 31% (RR 0·69, 95% CI 0·53-0·89) among women aged 25-29 years. Among boys aged 15-19 years anogenital wart diagnoses decreased significantly by 48% (RR 0·52, 95% CI 0·37-0·75) and among men aged 20-24 years they decreased significantly by 32% (RR 0·68, 95% CI 0·47-0·98). After 5-9 years of vaccination, CIN2+ decreased significantly by 51% (RR 0·49, 95% CI 0·42-0·58) among screened girls aged 15-19 years and decreased significantly by 31% (RR 0·69, 95% CI 0·57-0·84) among women aged 20-24 years. INTERPRETATION: This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects. FUNDING: WHO, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Condiloma Acuminado/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Condiloma Acuminado/prevenção & controle , Condiloma Acuminado/virologia , Determinação de Ponto Final , Feminino , Humanos , Incidência , Masculino , Vacinação em Massa , Papillomaviridae/classificação , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/farmacologia , Prevalência , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
2.
BMJ ; 365: l1161, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944092

RESUMO

OBJECTIVE: To quantify the effect on cervical disease at age 20 years of immunisation with bivalent human papillomavirus (HPV) vaccine at age 12-13 years. DESIGN: Retrospective population study, 1988-96. SETTING: National vaccination and cervical screening programmes in Scotland. PARTICIPANTS: 138 692 women born between 1 January 1988 and 5 June 1996 and who had a smear test result recorded at age 20. MAIN OUTCOME MEASURES: Effect of vaccination on cytology results and associated histological diagnoses from first year of screening (while aged 20), calculated using logistic regression. RESULTS: 138 692 records were retrieved. Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction (95% confidence interval 81% to 94%) in prevalent cervical intraepithelial neoplasia (CIN) grade 3 or worse (from 0.59% (0.48% to 0.71%) to 0.06% (0.04% to 0.11%)), an 88% reduction (83% to 92%) in CIN grade 2 or worse (from 1.44% (1.28% to 1.63%) to 0.17% (0.12% to 0.24%)), and a 79% reduction (69% to 86%) in CIN grade 1 (from 0.69% (0.58% to 0.63%) to 0.15% (0.10% to 0.21%)). Younger age at immunisation was associated with increasing vaccine effectiveness: 86% (75% to 92%) for CIN grade 3 or worse for women vaccinated at age 12-13 compared with 51% (28% to 66%) for women vaccinated at age 17. Evidence of herd protection against high grade cervical disease was found in unvaccinated girls in the 1995 and 1996 cohorts. CONCLUSIONS: Routine vaccination of girls aged 12-13 years with the bivalent HPV vaccine in Scotland has led to a dramatic reduction in preinvasive cervical disease. Evidence of clinically relevant herd protection is apparent in unvaccinated women. These data are consistent with the reduced prevalence of high risk HPV in Scotland. The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer. The findings will need to be considered by cervical cancer prevention programmes worldwide.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Neoplasia Intraepitelial Cervical/patologia , Diagnóstico Precoce , Feminino , Humanos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/prevenção & controle , Prevalência , Estudos Retrospectivos , Escócia/epidemiologia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
3.
Gynecol Oncol ; 152(3): 465-471, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30876490

RESUMO

OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.


Assuntos
Erradicação de Doenças/métodos , Modelos Teóricos , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Austrália , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Erradicação de Doenças/normas , Detecção Precoce de Câncer , Feminino , Política de Saúde , Humanos , Modelos Biológicos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/virologia , Adulto Jovem
4.
Expert Rev Vaccines ; 18(3): 309-322, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30739514

RESUMO

BACKGROUND: Substantial heterogeneity has been reported in efficacy against high-grade cervical intraepithelial neoplasia (CIN) irrespective of HPV type in phase III results for bivalent and quadrivalent human papillomavirus virus (HPV) vaccines (AS04-HPV and qHPV). Real-world data recently confirmed a very high overall impact of AS04-HPV, supporting the validity of the observed heterogeneity. To explore the reasons for heterogeneous efficacy, we assessed vaccine impact on high-grade lesions not caused by vaccine types. RESEARCH METHODS: We extracted case counts of CIN lesions containing (1) at least one vaccine HPV type, (2) at least one vaccine HPV type and a high-risk non-vaccine type (co-infections) and (3) no vaccine types (non-vaccine or no high-risk HPV types). Based on these, Phase III cross-protective efficacies were estimated with exclusion (3) and with inclusion (2 and 3) of co-infections. RESULTS: Cross-protective efficacy of AS04-HPV against CIN3 lesions ranges from 81.3% (95%CI: 34.7;96.5) (excluding co-infections) to 88.5% (95%CI:62.4;97.8) (including co-infections). For qHPV the efficacy ranges from -58.7% (95%CI: -180.5;8.5) (excluding co-infections) to 13.1% (95%CI: -39.0;45.9) (including co-infections). CONCLUSIONS: Heterogenous overall efficacy against CIN3 between AS04-HPV and qHPV is driven by differential efficacy against lesions that do not contain vaccine types, which may be related to the impact of different adjuvants on the immune response.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Neoplasia Intraepitelial Cervical/prevenção & controle , Ensaios Clínicos Fase III como Assunto , Feminino , Seguimentos , Humanos , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Adulto Jovem
5.
Obstet Gynecol Clin North Am ; 46(1): 107-123, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30683258

RESUMO

Cervical cancer disproportionately burdens lower-resourced settings, in which nearly 90% of cervical cancer and cervical cancer-related deaths occur. Targeting human papillomavirus (HPV) by prophylactic HPV vaccination in young adolescent girls and HPV-based screening in mid-adult women offers the most cost-effective strategy to reduce cervical cancer burden worldwide and mitigate the health disparities in cervical cancer burden between low-resourced and high-resourced settings. Political and social will, along with the necessary financial investments, will be necessary to realize the opportunity for significant global reductions in the cervical cancer burden. Perfect cervical cancer prevention (total eradication) is practically and financially unrealistic.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Programas de Rastreamento , Vacinação em Massa/economia , Infecções por Papillomavirus/complicações , Vacinas contra Papillomavirus/farmacologia , Neoplasias do Colo do Útero/prevenção & controle , Saúde da Mulher , Neoplasia Intraepitelial Cervical/diagnóstico , Análise Custo-Benefício , Feminino , Humanos , Programas de Rastreamento/economia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/economia , Neoplasias do Colo do Útero/diagnóstico
6.
Vaccine ; 37(3): 412-416, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30551987

RESUMO

Australia's transition to primary human papillomavirus (HPV) based cervical screening, has for the first time, provided a passive mechanism for monitoring the impact of vaccination on infection prevalence among women attending screening. We assessed oncogenic HPV prevalence by single year of age in the first 7  months of the program, using data collected from a large screening laboratory in Victoria, Australia, which is routinely screening using cobas 4800, cobas 6800 and Seegene assays. Among 116,052 primary screening samples from women aged 25-74, 9.25% (95%CI: 9.09-9.42%) had oncogenic HPV detected: 2.14% (95%CI: 2.05-2.22%) were 16/18 positive and 7.12% (95%CI: 6.97-7.27%) were positive for only non-16/18 HPV. Prevalence peaked at age 25-29 then decreased with age, but this was driven by non-16/18 types. HPV16/18 prevalence remained low and flat across ages, contrasting with pre-vaccination epidemiology when HPV16/18 peaked in young women. HPV-based screening can precisely monitor HPV prevalence.


Assuntos
Fatores Etários , Colo do Útero/virologia , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/uso terapêutico , Vacinação/estatística & dados numéricos , Adulto , Idoso , Austrália/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/prevenção & controle , Prevalência , Neoplasias do Colo do Útero/prevenção & controle
7.
BMC Womens Health ; 18(1): 200, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541542

RESUMO

BACKGROUND: Previous studies have shown that woman attending their first cervical screening or colposcopy appointment experience negative emotions, primarily anxiety and fear. With the introduction of the Human Papillomavirus (HPV) vaccine, it is unknown whether these emotions will have altered or whether the information needs of vaccinated women will have changed. The objective of this study is to determine the knowledge, understanding and concerns that young women have about HPV when attending colposcopy and whether their information needs are met. METHODS: This is a qualitative study using semi-structured interviews which were audiotaped and transcribed. Data was analysed thematically, with recruitment until data saturation was reached. Women born after 01/09/1990 and attending colposcopy as a result of abnormal cytology were eligible to join the study. Recruitment took place in an out-patient regional colposcopy clinic, Aberdeen, Scotland. RESULTS: Fifteen women were interviewed. The majority of participants had some knowledge and understanding of HPV, cervical screening and colposcopy. Knowledge about the HPV vaccine was more limited; a third of participants misunderstood the effectiveness of the vaccine believing that is provided complete protection, and were left feeling that it had failed them. Some also felt that they were "test cases" for the vaccine. CONCLUSION: With the introduction of the HPV vaccine, the information and support needs of young women attending colposcopy are not fully met, leaving women with unanswered questions. With increasing numbers of vaccinated women entering the screening programme, it is timely to review the information available to these women.


Assuntos
Neoplasia Intraepitelial Cervical/psicologia , Colposcopia/psicologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Vacinas contra Papillomavirus , Instituições de Assistência Ambulatorial , Ansiedade/prevenção & controle , Neoplasia Intraepitelial Cervical/prevenção & controle , Feminino , Humanos , Infecções por Papillomavirus/psicologia , Pesquisa Qualitativa , Adulto Jovem
9.
JAMA ; 320(1): 43-52, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29971397

RESUMO

Importance: There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations. Objective: To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control). Design, Setting, and Participants: Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible. Interventions: A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing. Main Outcomes and Measures: The primary outcome was the cumulative incidence of CIN3+ 48 months following randomization. The cumulative incidence of CIN2+ was a secondary outcome. Results: Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). The CIN2+ incidence rate at 48 months was 5.0/1000 (95% CI, 3.8-6.7) in the intervention group and 10.6/1000 (95% CI, 8.7-12.9) in the control group. The CIN2+ risk ratio was 0.47 (95% CI, 0.34-0.67). Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 [95% CI, 0.8-2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13-0.48]). Conclusions and Relevance: Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness. Trial Registration: isrctn.org Identifier: ISRCTN79347302.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Adulto , Idoso , Neoplasia Intraepitelial Cervical/prevenção & controle , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias do Colo do Útero/prevenção & controle
10.
Pol J Pathol ; 69(1): 42-47, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895125

RESUMO

Cervical cancer is the third most common malignant neoplasm in women worldwide. HPV infection is the necessary factor for the cancer to develop. HPV DNA can be integrated into the genome of squamous epithelium and cause transcription of the viral oncoproteins and development of invasive cancer within 15-20 years. We assessed ICC co-expression of p16/Ki-67 proteins in smears collected from the uterine cervix and the association between p16/Ki-67 co-expression and cytologic and histologic results. Samples were collected from 93 women using liquid based cytology (LBC). Two microscopic slides were prepared: for Papanicolaou staining and ICC staining. Biopsy samples were collected from 43 women. Diagnosis of CIN 2+ was the endpoint of the study. p16/Ki-67 positive cells were found in women with: 1) a cytology result of ASC-US (3.59%), LSIL (2.22%), ASC-H (21.92%), HSIL (33.18%), SCC (72.22%) or NILM (3.44%); 2) a histopathologic result of CIN 1 (2.13%), CIN 2 (19.93%), CIN 3 (23.22%), SCC (69.72%) or normal histology (7.58%). p16/Ki-67 dual staining can increase the efficiency of screening methods and indicate women in whom further diagnostic procedures are required or those with extremely low risk of cancer. Sparing protocols will have a significant role in women of reproductive age.


Assuntos
Células Escamosas Atípicas do Colo do Útero/química , Neoplasia Intraepitelial Cervical/química , Inibidor p16 de Quinase Dependente de Ciclina/análise , Detecção Precoce de Câncer/métodos , Antígeno Ki-67/análise , Lesões Pré-Cancerosas/metabolismo , Prevenção Secundária/métodos , Neoplasias do Colo do Útero/química , Adolescente , Adulto , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
11.
Anticancer Res ; 38(5): 3079-3084, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29715143

RESUMO

BACKGROUND/AIM: This study gives an insight into recent trends for Human papillomavirus (HPV)-specific infection and its fluctuation over the years 2011-2016. MATERIALS AND METHODS: A total of 2,417 Caucasian women between the age of 18 and 71 years underwent their annual gynaecologic examination at the Outpatient Gynaecological Clinic in the study period. RESULTS: Overall HPV prevalence was 43.9%, and high-risk HPV accounted for 31.3%. HPV16 was the most common high-risk type followed by HPV51 and HPV31. HPV positivity was higher in those with low- and high-grade squamous intraepithelial lesions (HSILs) than in women with a normal cytological test. HPV infection was highest in 2011.The prevalence of single infections remained higher than multiple infections over the entire study period. HPV16 prevalence was very high in the first years of the study and HPV18 exhibited highest prevalence in 2011. Younger women exhibited a significant increase in HPV infection from 2014. Overall HPV infection decreased over the study period. CONCLUSION: These data suggest that HPV vaccination might reduce the frequency of HSILs and cervical cancer and are useful for the development of a national screening programme.


Assuntos
Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Feminino , Grécia/epidemiologia , Humanos , Pessoa de Meia-Idade , Vacinas contra Papillomavirus/uso terapêutico , Prevalência , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/prevenção & controle , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
12.
Vaccine ; 36(24): 3423-3426, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735324

RESUMO

Therapeutic HPV vaccine is an agent to induce E7-specific Th1 immune responses to treat cervical neoplasia (CIN2-3). Our previous clinical trial has demonstrated that oral administration of HPV16 E7-expressing Lactobacillus casei (L. casei), GLBL101c, resulted in the regression of HPV16-related CIN3. Here we examined optimization of the E7-expressing L. casei for induction of the mucosal immune responses to E7. Various doses of HPV16 E7 molecule were displayed on the L. casei. Immunization with E7-bound L. casei showed the induction of E7-specific mucosal IFNγ-producing cells was dependent on displayed E7-doses but saturated beyond 0.3 µg/108 cells. A new agent, L. casei with endogenous expression of E7 (IGMKK16E7), showed the optimal amount of displayed-E7. Immunization with IGMKK16E7 demonstrated 4-fold higher induction of E7-specific mucosal IFNγ-producing cells when compared with the former one. Our new system provided the optimal E7-expressing L. casei for displayed-E7 amount and induction of mucosal Th1 immune response.


Assuntos
Antígenos Virais/imunologia , Papillomavirus Humano 16/imunologia , Interferon gama/biossíntese , Lactobacillus casei/imunologia , Proteínas E7 de Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Células Th1/imunologia , Administração Oral , Animais , Antígenos Virais/genética , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Relação Dose-Resposta Imunológica , Feminino , Expressão Gênica , Engenharia Genética , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Papillomavirus Humano 16/genética , Humanos , Imunidade nas Mucosas , Imunização/métodos , Interferon gama/metabolismo , Lactobacillus casei/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/genética , Células Th1/virologia , Transgenes/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
13.
Cochrane Database Syst Rev ; 5: CD009069, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29740819

RESUMO

BACKGROUND: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. OBJECTIVES: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. SEARCH METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. SELECTION CRITERIA: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). DATA COLLECTION AND ANALYSIS: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. MAIN RESULTS: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). AUTHORS' CONCLUSIONS: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Lesões Pré-Cancerosas/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/mortalidade , Neoplasia Intraepitelial Cervical/virologia , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Vacinas contra Papillomavirus/efeitos adversos , Lesões Pré-Cancerosas/mortalidade , Lesões Pré-Cancerosas/virologia , Gravidez , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
14.
BMC Cancer ; 18(1): 273, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523108

RESUMO

BACKGROUND: Cervical cancer screening participation remains insufficient in most countries. Our aim was to evaluate whether offering a HPV self-sampling kit, either mailed directly to the woman's home or using timely opt-in procedures for ordering the kit, increased screening participation compared with a standard second reminder. METHODS: In this randomized, controlled effectiveness trial, 9791 Danish women aged 30-64 who were due to receive the second reminder were equally randomized to either: 1) direct mailing of a second reminder and a self-sampling kit (directly mailed group); 2) mailing of a second reminder that offered a self-sampling kit to be ordered by e-mail, text message, phone, or webpage (opt-in group); or 3) mailing of a second reminder to attend regular cytology screening (control group). In an intention-to-treat analysis, we estimated the participation rate at 180 days post intervention, by returning a self-sample or attending regular cytology screening. We calculated the proportion of women with a positive HPV self-sample who attended for cervical cytology triage at the general practitioner within 90 days. RESULTS: Participation was significantly higher in the directly mailed group (38.0%) and in the opt-in group (30.9%) than in the control group (25.2%) (participation difference (PD): 12.8%, 95% CI: 10.6-15.0% and PD: 5.7%, 95% CI: 3.5-7.9%, respectively). Within 90 days, 107 women (90.7%, 95% CI: 83.9-95.3%) with a HPV-positive self-sample attended follow-up. CONCLUSIONS: Offering the opportunity of HPV self-sampling as an alternative to regular cytology screening increased participation; the direct mailing strategy was the most effective invitation strategy. A high compliance with follow-up was seen. TRIAL REGISTRATION: Current Controlled Trials NCT02680262 . Registered 10 February 2016.


Assuntos
Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/complicações , Participação do Paciente , Serviços Postais/estatística & dados numéricos , Autocuidado , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prevalência , Prognóstico , Projetos de Pesquisa , Manejo de Espécimes , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
15.
J Low Genit Tract Dis ; 22(2): 123-125, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29474243

RESUMO

Cervical cancer prevention guidelines are benchmarked to risk of cervical precancer. In younger age cohorts, vaccination against high-risk types of human papillomavirus (HPV) has reduced HPV 16/18 prevalence and cervical intraepithelial neoplasia. Lower prevalence of precancer will impair the sensitivity of cytology and colposcopy, but negative predictive value will rise. Training and skills maintenance will become more difficult as abnormalities become less common. Primary screening with HPV assays will become more attractive but will require HPV genotyping as most positive HPV tests will reflect non-16/18 infections with lower oncogenicity. Screening will begin later and will occur at longer intervals. Colposcopy and treatment thresholds will become more stringent. Historical data sets will become inappropriate for guidelines development. As women immunized using nonavalent vaccine reach screening age, these trends will become still more pronounced.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/prevenção & controle , Competência Clínica , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Detecção Precoce de Câncer , Feminino , Humanos , Vacinas contra Papillomavirus/uso terapêutico , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Saúde da Mulher , Adulto Jovem
16.
J Med Virol ; 90(1): 148-156, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28661048

RESUMO

Human papillomavirus (HPV) is one of the most common sexually transmitted infectious pathogens. Persistent infection has been linked to cancer development, in particular to cervical cancer. This study aims to investigate the epidemiology of HPV infection in women in Inner Mongolia of China and to dissect the disparities between the Han and Mongolian ethnic populations. Cervical cell samples from 5655 women (17-68 years old) were collected during routine gynecologic examination. HPV infection was established using the HPV GenoArray kit detecting 21 HPV genotypes. The overall HPV prevalence was 14.5%. HPV16 (5.0%), HPV58 (2.2%), and HPV52 (1.5%) are the most common genotypes. Of the 21 genotypes investigated, high-risk HPV genotypes dominate in all age groups. HPV16 and HPV58 are the most common genotypes in patients with cervical lesions. HPV prevalence among Han women is 11.5% and the most common genotypes are HPV16 (4%) and HPV58 (2.1%). HPV prevalence is significantly higher in Mongolian women (32.6%), with the most common genotypes being HPV16 (10.7%), HPV31 (7.1%), and HPV52 (4.3%). The multiple infection rate in Mongolian participants (14.9%) is also higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian participants. HPV infection is highly prevalent in women in Inner Mongolia, China. HPV16 remains the most common genotype in this area. However, there are clear ethnical disparities in respect to the HPV epidemiology between the Han and Mongolian population.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/etnologia , Vigilância da População , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Colo do Útero/citologia , Colo do Útero/virologia , China/epidemiologia , Grupos Étnicos , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Parceiros Sexuais , Urbanização , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-28958633

RESUMO

HIV-related immunodeficiency has complex effects on female genital HPV, which include increased risks of infection, multiple types, persistence, reactivation and the risk to develop pre-invasive and invasive disease. Reconstitution of immunity with anti-viral drugs improves cellular immunity, but the risk of HPV-related malignancy remains higher than background incidences and presents at younger ages. Early initiation of antiretroviral therapy (ART) allows improved retention of immune memory through existing antibodies and T-cell clones and improves long-term outcomes. Suggestions of a higher risk to contract HIV if there is existing genital HPV infection are supported and explained by pathophysiological cervical changes, including inflammation. HIV-HPV interactions should influence public health decisions towards prioritising large-scale prepubertal HPV-vaccine roll-out, secondary cervical cancer prevention and early detection programmes for HIV-infected women and early initiation of ART. This chapter will also focus on special considerations for the management of women with co-infection with these two viruses and genital HPV-related diseases.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Coinfecção/virologia , Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/prevenção & controle , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Neoplasia Intraepitelial Cervical/virologia , Coinfecção/prevenção & controle , Coinfecção/terapia , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Imunocompetência , Programas de Rastreamento , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/transmissão , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/virologia , Fatores de Risco , Neoplasias do Colo do Útero/virologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-28986092

RESUMO

Persistent oncogenic human papillomavirus (HPV) is the cause of cervical cancer, as well as cancers of the anus, penis, vulva, vagina and oropharynx. There is good evidence that prophylactic HPV vaccines are immunogenic and effective against targeted-type HPV infections and type-specific genital lesions, including high-grade cervical intraepithelial neoplasia (CIN), when administered prior to HPV infection. There is good evidence that HPV vaccines are safe in population usage, with the most frequent adverse event being injection-site reactions. There is evidence to support some cross-protection against non-targeted types occurring following the administration of HPV vaccines. There is limited evidence suggesting that HPV vaccines may be beneficial in preventing future disease in women treated for high-grade CIN. This chapter focuses on the accumulated evidence regarding the global use of the three licensed HPV vaccines including safety, immunogenicity, duration of protection, effectiveness, coverage to date and barriers to higher coverage.


Assuntos
Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Cobertura Vacinal/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Distribuição por Idade , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Tomada de Decisões , Feminino , Saúde Global , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Gravidez , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/efeitos adversos
19.
Artigo em Inglês | MEDLINE | ID: mdl-28988647

RESUMO

Cervical cancer affects women in their reproductive ages. Screening is an important secondary prevention strategy. The long process of carcinogenic transformation from human papillomavirus (HPV) infection to invasive cancer provides ample opportunities to detect the disease at a stage when treatment is highly effective. Suitable screening tests are cytology, visual inspection after acetic acid application and HPV detection tests. Evidence of effectiveness of the tests to reduce cervical cancer mortality and the cost-effectiveness of screening programs have been demonstrated. Cervical intraepithelial neoplasia grade 2 and grade 3 are the high-grade cervical cancer precursors and need to be treated. Treatment is safe and effective with ablative or excisional techniques. The World Health Organization recommends screening women at least once in a lifetime between 30 and 49 years of age and ensuring effective treatment of the detected abnormalities. Combination of HPV vaccination and population-based screening will be instrumental in eliminating cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Prevenção Secundária , Neoplasias do Colo do Útero/prevenção & controle , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/mortalidade , Progressão da Doença , Feminino , Carga Global da Doença , Humanos , Programas de Rastreamento/economia , Teste de Papanicolaou/economia , Teste de Papanicolaou/estatística & dados numéricos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Esfregaço Vaginal/economia , Esfregaço Vaginal/estatística & dados numéricos
20.
Artigo em Inglês | MEDLINE | ID: mdl-29108943

RESUMO

High-risk human papillomavirus (HPV) infection is known to be a necessary factor for cervical and anogenital malignancies. Cervical cancers account for over a quarter of a million deaths annually. Despite the availability of prophylactic vaccines, HPV infections remain extremely common worldwide. Furthermore, these vaccines are ineffective at clearing pre-existing infections and associated preinvasive lesions. As cervical dysplasia can regress spontaneously, a therapeutic HPV vaccine that boosts host immunity could have a significant impact on the morbidity and mortality associated with HPV. Therapeutic vaccines differ from prophylactic vaccines in that they are aimed at generating cell-mediated immunity rather than neutralising antibodies. This review will cover various therapeutic vaccine strategies in development for the treatment of HPV-associated lesions and cancers.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Papillomaviridae , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Vacinas Anticâncer/uso terapêutico , Neoplasia Intraepitelial Cervical/terapia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Saúde Global , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/economia , Vacinas contra Papillomavirus/genética , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Cobertura Vacinal
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