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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.
Int J Gynecol Cancer ; 30(8): 1097-1100, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487685
3.
BMC Public Health ; 20(1): 671, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398057

RESUMO

BACKGROUND: An infection with high-risk human papillomavirus (HPV) is the obligatory aetiological factor for the development of cervical cancer. In Switzerland, the prevention strategy for cervical cancer is based on primary prevention via HPV vaccination and secondary prevention with an opportunistic screening programme for precancerous lesions. Vaccination is recommended to 11-26 years old male and female persons. The objective of the study was to assess the epidemiological impact on cervical cancer of switching from the currently implemented programme with the 4-valent vaccine to the 9-valent vaccine, in an 11-26 years old gender-neutral vaccination programme in Switzerland. METHODS: A previously validated dynamic transmission model of HPV infections was adapted and calibrated to the Swiss setting assuming an 80% coverage rate in HPV-vaccination and lifelong vaccine type-specific protection. A gender-neutral vaccination programme (males and females) for 11-26 years old with a 9-valent HPV vaccine was compared with the current 11-26 years old gender-neutral 4-valent vaccination programme. Sensitivity analyses were conducted in order to test the impact of lower vaccination coverage rates and a shorter duration of protection on the model outcomes. RESULTS: In Switzerland, a 9-valent gender-neutral vaccination programme would result in an additional prevention of 2979 cervical cancer cases, 13,862 CIN3 and 15,000 CIN2 cases, compared with the 4-valent gender-neutral vaccination programme over 100 years. These additional disease cases avoided would correspond to a 24, 36 and 48% cumulative incidence decrease in cervical cancer, CIN3 and CIN2 cases, respectively. It would also prevent additional 741 cervical cancer-related deaths over 100 years. A substantial additional reduction in cervical cancer and precancerous lesions burden is still observed when varying the vaccination coverage rate from 30 to 60% or reducing the duration of protection from lifelong to 20 years. CONCLUSIONS: The switch to the 9-valent vaccine in Switzerland to prevent cervical diseases showed an important contribution in terms of public health impact compared with the 4-valent vaccine in an 11-26 years old gender-neutral population, even with very conservative assumptions such as low coverage rates or low duration of protection and limiting analysis to only cervical disease.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Programas de Imunização/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/economia , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Criança , Análise Custo-Benefício , Feminino , Humanos , Incidência , Programas de Rastreamento/estatística & dados numéricos , Suíça/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem
4.
Int J Gynaecol Obstet ; 150(1): 108-115, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32342504

RESUMO

OBJECTIVE: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence. METHODS: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015. RESULTS: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%. CONCLUSION: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer.


Assuntos
Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Vacinas contra Papillomavirus/imunologia , Adulto , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Feminino , Infecções por HIV/virologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/estatística & dados numéricos
5.
Artigo em Inglês | MEDLINE | ID: mdl-32291178

RESUMO

Cytology-based cervical screening had unequivocal success in reducing the incidence and mortality of cervical cancer in the last century. The recognition of the role of human papillomavirus (HPV) as a necessary cause of cervical cancer led to the development of HPV testing. Gradually, there has been a shift from reflex HPV testing for mild cytological abnormalities, to co-testing with cytology and HPV, and lately to primary HPV screening, based on evidence from well-designed large randomized controlled trials and meta-analyses. Advantages of primary HPV screening include higher sensitivity to detect pre-neoplastic lesions, better re-assurance with a negative test, and safe prolongation of screening intervals. However, clinicians and policy makers must ensure the availability of clinically validated HPV assays and triage protocols of screen positive cases prior to implementation of primary HPV screening. This is likely to reduce potential harm from over-treatment as well as extra burden on the health care system.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
6.
Am J Obstet Gynecol ; 223(3): 408.e1-408.e11, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32109465

RESUMO

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Colposcopia/normas , Recidiva Local de Neoplasia/prevenção & controle , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Sociedades Médicas , Estados Unidos , Neoplasias do Colo do Útero/patologia , Adulto Jovem
7.
Cancer ; 126(8): 1656-1667, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32037524

RESUMO

BACKGROUND: Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology. METHODS: This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up. RESULTS: The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively. CONCLUSIONS: The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/imunologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Criança , Gerenciamento de Dados , Feminino , Humanos , Estudos Retrospectivos , Estados Unidos , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Adulto Jovem
8.
N Z Med J ; 133(1508): 72-84, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945044

RESUMO

AIM: Determine the impact of quadrivalent human papillomavirus (HPV) vaccination on abnormal cervical cytology and histology rates in young New Zealand women. METHODS: Retrospective population-based cohort study of women born 1990-1994, with a cervical cytology or histology recorded when aged 20-24 between 1 January 2010 and 31 December 2015. Data was obtained through linking the National Immunisation Register and National Cervical Screening Programme Register. RESULTS: N=104,313 women (376,402 person years of follow up) were included. The incidence of high-grade cytology was lower in vaccinated women (at least one dose prior to 18 years) than in unvaccinated women (8.5 vs 11.3 per 1,000 person years [p1000py], incidence rate ratio [IRR 0.75], 95% CI 0.70, 0.80, p<.001). The incidence of high-grade histology was lower in vaccinated women than in unvaccinated women (6.0 vs 8.7 p1000py, IRR 0.69, 95% CI 0.64, 0.75, p<.001). There was no evidence of a difference in the incidence of high-grade histology between European and Maori women overall or after taking vaccination status into account. CONCLUSIONS: Receiving at least one dose of quadrivalent HPV vaccine prior to 18 years was associated with a 25% lower incidence of high-grade cytology and 31% lower incidence of high-grade histology in women aged 20-24 years.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Incidência , Programas de Rastreamento/métodos , Nova Zelândia/epidemiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Adulto Jovem
9.
J Womens Health (Larchmt) ; 29(4): 596-602, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31532298

RESUMO

Objective: Women without regular health care providers or a medical home routinely fail to complete recommended cervical cancer screening. At-home self-collection of samples to test for high-risk strains of human papillomavirus (hrHPV) can improve screening rates. This study documents acceptability and feasibility of community lay navigator (LN)-facilitated at-home self-collection for underscreened women in Appalachian Virginia. Materials and Methods: This study used mixed methods in three phases. Phase I involved focus groups of LNs to ensure cultural acceptability of self-collection, and to enhance recruitment of medically underserved women. An environmental scan of community resources and climate was created in Phase II. During Phase III, underscreened women in Appalachian Virginia (the far southwest corner of Virginia) were recruited to complete hrHPV testing using LN-provided self-collection kits. Results: LN-facilitated at-home self-collection for HPV testing was deemed culturally acceptable and feasible to participants in this community-based pilot study. Self-kit training included 64 LNs, of which 35 engaged in the study and were provided 77 kits and instructions. A total of 59 self-kits were returned, of which 42 were correctly completed with valid HPV results, yielding a 16.6% hrHPV rate. Conclusions: Over a quarter of the women LNs recruited had no medical home, indicating this delivery model may have potential to reach women at increased risk of being underscreened for cervical cancer. Research is needed to identify optimal approaches to increase LN participation in outreach self-collection interventions.


Assuntos
Agentes Comunitários de Saúde , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde , Manejo de Espécimes/métodos , Adulto , Região dos Apalaches , Neoplasia Intraepitelial Cervical/prevenção & controle , Estudos de Viabilidade , Feminino , Acesso aos Serviços de Saúde , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Teste de Papanicolaou/métodos , Papillomaviridae/isolamento & purificação , Projetos Piloto , Autocuidado/métodos , Inquéritos e Questionários , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal/métodos , Virginia
10.
Am J Epidemiol ; 189(4): 265-276, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-31680146

RESUMO

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


Assuntos
Adenocarcinoma in Situ/prevenção & controle , Neoplasia Intraepitelial Cervical/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Adenocarcinoma in Situ/virologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/virologia , Feminino , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Humanos , Vigilância da População , Neoplasias do Colo do Útero/virologia , Adulto Jovem
11.
Int J Cancer ; 146(3): 810-818, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980692

RESUMO

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adenocarcinoma in Situ/prevenção & controle , Adenocarcinoma in Situ/virologia , Adolescente , Adulto , Fatores Etários , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/isolamento & purificação , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Pré-Cancerosas/prevenção & controle , Lesões Pré-Cancerosas/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
12.
Am J Pathol ; 189(12): 2459-2468, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732107

RESUMO

Cervical dysplastic lesions called cervical intraepithelial neoplasias (CINs) need be treated to prevent cervical cancer. Currently available surgical procedures are effective, but the development of noninvasive treatment is warranted. In human papillomavirus transgenic mice engineered to express human papillomavirus type 16 E6 and E7, short-term treatment with 17ß-estradiol induces CINs that progress to cervical cancer if the treatment is continued. In the present study, this mouse model was used to determine whether medroxyprogesterone acetate (MPA), a progestin drug, is chemopreventive. Human papillomavirus transgenic mice bearing CIN lesions were treated with MPA plus 17ß-estradiol. Unlike control mice treated with 17ß-estradiol alone, cervical cancer was absent in the MPA-treated mice. This observation suggests that MPA prevented CIN from progressing to invasive cancer. MPA was associated with inhibited cell proliferation and the promotion of apoptosis in CIN lesions. Confirming the role of the progesterone receptor, the preventive effect of MPA was absent in human papillomavirus transgenic mice in which the expression of progesterone receptor was genetically ablated. These results suggest that MPA is efficient in treating progesterone receptor-positive CIN lesions. These findings provide the basis for a biomarker-driven clinical trial of the secondary prevention of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Acetato de Medroxiprogesterona/farmacologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Receptores de Progesterona/metabolismo , Neoplasias do Colo do Útero/prevenção & controle , Animais , Antineoplásicos Hormonais/farmacologia , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
13.
BMC Public Health ; 19(1): 1514, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718611

RESUMO

BACKGROUND: Cervical cancer was the fourth most common cancer among women worldwide in 2012 and was the eighth most common cancer in 2014 and the eighth greatest cause of female cancer deaths in Hong Kong in 2015. Human papillomavirus (HPV) vaccination has been clinically documented to have a high efficacy in reducing HPV-related cervical intraepithelial neoplasia incidence. Therefore, receiving vaccination is a crucial public health measure to reduce disease burden. Significant others, such as schools and schoolteachers, have prominent influence in shaping adolescents' health perceptions and behavior. Therefore, the perspective of schools and schoolteachers regarding vaccination can significantly influence students' acceptance and accessibility of the vaccine. However, few studies have analyzed the perceptions of schoolteachers toward HPV vaccination, and even fewer have concerned how schoolteachers' perceptions influence their schools' motivation in implementing school-based HPV vaccination programs. This study was thus conducted to fill this literature gap. METHODS: With a Chinese community as the field site of this study, a qualitative approach of five focus group interviews was conducted with 35 schoolteachers from five primary and eight secondary schools in Hong Kong between July 2014 and January 2015. Thematic content analysis was used for data analysis. RESULTS: Perceptual, institutional, student and parental, and collaborator barriers interacted to discourage the sampled schoolteachers from organizing school-based HPV vaccination programs. Lack of knowledge regarding HPV vaccination, perception of HPV vaccination as inappropriate given the students' age, violation of traditional cultural values, lack of perceived needs and perceived risk, opposition from schools, low priority of HPV vaccination over other health education topics, lack of government support, lack of interest from parents and students, and lack of confidence in implementing organizations, all were the mentioned barriers. CONCLUSIONS: The sampled schoolteachers were demotivated to organize school-based HPV vaccination programs because of their perceptions and various social and cultural factors. As significant influencers of adolescent students, schoolteachers and schools should receive more support and information on organizing school-based HPV vaccination programs in the future.


Assuntos
Neoplasia Intraepitelial Cervical/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Professores Escolares , Instituições Acadêmicas , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Neoplasia Intraepitelial Cervical/virologia , Criança , Feminino , Educação em Saúde , Hong Kong/epidemiologia , Humanos , Programas de Imunização , Masculino , Motivação , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Pesquisa Qualitativa , Serviços de Saúde Escolar , Estudantes , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
14.
Jpn J Clin Oncol ; 49(9): 877-880, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613356

RESUMO

We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.


Assuntos
Papillomavirus Humano 16 , Imunoterapia , Proteínas E7 de Papillomavirus/imunologia , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/terapia , Adulto , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Método Duplo-Cego , Feminino , Humanos , Imunidade nas Mucosas , Lactobacillus/genética , Pessoa de Meia-Idade , Lesões Intraepiteliais Escamosas Cervicais/imunologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
15.
Asian Pac J Cancer Prev ; 20(10): 2987-2994, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31653145

RESUMO

OBJECTIVE: Evaluation of prevalence and risk factors of cervical dysplasia among Human Immunodeficiency Virus sero-positive (HIV+ve) females on Highly Active Antiretroviral Therapy (HAART) attending HIV clinic at University of Nigeria Teaching Hospital (UNTH) Enugu, Southeastern, Nigeria. METHODS: Structured questionnaire was used to obtain socio-demographic and risk factors data. Cervical specimens were collected from 105 HIV +ve females on HAART and 104 HIV seronegative (HIV-ve) females. Pap smears were collected using cytobrush and Ayre's spatula in a secluded place. Smears were made on slides and placed in 95% ethyl alcohol for conventional Pap staining and the cytobrush washed into the preservative containers for later Immunocytochemistry staining. Blood samples were used for HIV screening. Immunocytochemistry activity using anti-P16INK4A was carried out on the Pap smears that were positive for cervical dysplasia. RESULTS: Pap staining showed prevalence of cervical dysplasia among HIV+ve on HAART 19.05%, (ASCUS 14.29%, LSIL 3.81%, HSIL 0.95%) whereas HIV-ve was 6.73%, p = 0.008. Only the HSIL 0.95% was positive for P16INK4A. Odds ratios at 95% Confident Interval of the risk factors of cervical dysplasia were thus; HIV+ve, 3.26 (1.31-8.09), education less than secondary school 3.23 (1.25-8.37), polygamy 3.23 (1.25-8.37), smoking 1.36 (0.15-12.10), married 2.08 (0.43-2.31), grand multi gravidity 1.72 (0.72-4.11), grand multi parity 1.54 (0.66-3.61), positive history of sexually transmitted diseases 2.49 (1.06-5.80). Uptake of cervical cancer screening was low in both study groups, 7 (6.7%) among HIV+ve on HAART and 14 (13.5%) among HIV-ve females, P = 0.102. CONCLUSION: HAART had cytoprotective effect against cervical dysplasia in HIV+ve females, by reducing progression of ASCUS to LSIL, HSIL and cervical cancer. Progression from normal to ASCUS increased which could be due to latency or/and prolonged persistent high risk HPV and HIV infections, of the most sexually active age group before diagnosed of HIV.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , HIV/efeitos dos fármacos , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Seguimentos , Infecções por HIV/virologia , Humanos , Nigéria/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
16.
Papillomavirus Res ; 8: 100177, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31319173

RESUMO

AIM: Prophylactic human papillomavirus (HPV) vaccines are highly effective at preventing pre-cancerous cervical lesions when given in a three-dose schedule. Some post-hoc trial data suggest that one dose prevents HPV infection. If one dose could prevent pre-cancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated. We assessed the effectiveness of quadrivalent HPV vaccine by number of doses against cervical intraepithelial neoplasia (CIN) 2 or 3/adenocarcinoma-in-situ (AIS)/cancer in Australia up to seven years post vaccination. METHODS: We linked registry data from all 8 jurisdictional cervical screening registers, with the national HPV vaccination register, death index and cancer registers for all Australian women aged 15 or under when eligible for vaccine who screened between April 2007 (when vaccination commenced) and 31 December 2014. We performed Cox proportional hazard regression, adjusted a priori for age, socioeconomic status, and area of residence, to estimate hazard ratios of histologically confirmed CIN2/CIN3/AIS/cancer. RESULTS: We included 250,648 women: 48,845 (19·5%) unvaccinated, 174,995 (69·8%) had received three doses, 18,190 (7·3%) two doses and 8,618 (3·4%) one dose. The adjusted hazard ratio was significantly lower for all dose groups compared to unvaccinated women (1 dose 0·65 (95%CI 0·52-0·81), 2 doses 0·61 (0·52-0·72) and 3 doses 0·59 (0·54-0·65).) With adjustment for age at vaccination amongst the vaccinated group, the adjusted hazard ratios for one dose and two dose recipients were comparable to three dose recipients (one dose 1.01 (95%CI 0.81-1.26), two doses 1.00 (0.85-1.17).) Multiple sensitivity analyses, including use of different dose assignment methods, produced consistent findings. Comparison with a historical cohort of age matched women showed that the result was not due to herd protection alone. CONCLUSIONS: One dose had comparable effectiveness as two or three doses in preventing high-grade disease in a high coverage setting. These findings support the hypothesis that one dose vaccination may be a viable strategy when working towards the global elimination of cervical cancer.


Assuntos
Alphapapillomavirus/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Austrália/epidemiologia , Neoplasia Intraepitelial Cervical/etiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Vacinação , Adulto Jovem
17.
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
18.
Vaccine ; 37(31): 4262-4267, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31248688

RESUMO

BACKGROUND: Incidence of high-grade cervical lesions (HGCL) has declined in the U.S following the introduction of the human papillomavirus (HPV) vaccine in 2006. However, many women continue to be diagnosed with HGCLs, including those eligible to receive the vaccine but did not. We determined self-reported barriers to and correlates of HPV vaccination in vaccine-eligible women diagnosed with cervical intraepithelial neoplasia grades 2, 2/3, 3 and adenocarcinoma in situ (CIN2+). METHODS: Data from a statewide surveillance system in Connecticut for CIN 2+ during 2008-2015 were used for this analysis. Enhanced surveillance data were collected for women residing in New Haven County, including HPV vaccine history and demographic factors, through chart review and patient interviews. Women who reported being unvaccinated were asked why they did not receive the vaccine. We evaluated trends in reasons for not receiving the vaccine using a two-sided Cochran Armitage trend test. Log-binomial analysis was used to assess associations between sociodemographic characteristics and vaccination status. RESULTS: Between 2008 and 2015, 1625 vaccine-eligible women were diagnosed with CIN2+, with 882 of these women reporting never receiving the HPV vaccine. The proportion of unvaccinated vaccine-eligible women did not significantly change from 2008 to 2015 (p = 0.18, range 49.1% to 60.0%). The most commonly reported reason for being unvaccinated was age/too old, followed by previous HPV diagnosis and no provider recommendation. Women who had public or no insurance were significantly more likely than privately insured women to report being unvaccinated (p = <0.001, p = 0.0034). CONCLUSIONS: Commonly cited barriers to vaccination, such as age/too old and previous HPV diagnosis, are not contraindications for vaccination. Furthermore, frequent reporting of no provider recommendation underscores the important role providers play in the immunization of their patients. These results indicate the need for greater efforts by providers to dispel myths about HPV vaccine eligibility and to promote vaccination for all of their eligible patients.


Assuntos
Infecções por Papillomavirus/complicações , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Vacinação , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/etiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Connecticut/epidemiologia , Feminino , Humanos , Incidência , Seguro Saúde , Avaliação de Resultados em Cuidados de Saúde , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Prevalência , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
19.
Eur J Cancer ; 116: 21-26, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31163338

RESUMO

Vaccines against human papillomavirus (HPV) are available in Europe since 2006. They have been highly effective in preventing infection and disease caused by the vaccine types. Clinical efficacy data are available for cervical, vulvovaginal and anal precancer and invasive cervical cancer. Disease reduction is best with early vaccination and a coverage of more than 70%. Gender-neutral vaccination provides direct protection for all men and improves the coverage. A good coverage is followed by herd protection of the unvaccinated men and women. School-based programs appear to be most effective; under the age of 15 years, two doses with an interval of 6-12 months are sufficient. From the age of 15 years, the standard regimen with three doses is recommended. A broad catch-up program for young adult women and men improves the effectiveness. The vaccines are also effective in sexually active women and men with previous but cleared infections. Vaccination in addition to local treatment of HPV-related disease appears to reduce recurrent or subsequent HPV-related disease. Combination of HPV vaccination and screening with HPV testing is the most effective approach to prevention of cervical cancer. The screening intervals may increase in the vaccinated cohorts. The upper age limit for vaccination remains to be evaluated, is country specific and depends on cost-effectiveness. The European Society of Gynaecologic Oncology and the European Federation for Colposcopy strongly support gender-neutral vaccination programs for children and young adolescents, with a catch-up program for young adults.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Europa (Continente) , Feminino , Humanos , Masculino , Infecções por Papillomavirus/complicações
20.
BMJ Open ; 9(4): e025388, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036707

RESUMO

OBJECTIVES: Human papillomavirus (HPV) testing in cervical screening offers the potential for self-sampling to improve uptake among non-attenders. High-risk (HR) HPV detection in urine shows promise, but few studies have examined its sensitivity for cervical intraepithelial neoplasia (CIN2+) detection compared with standard cervical samples. The aims of this cross-sectional study were to optimise conditions for urine testing for HPV detection; to determine concordance for HR-HPV detection in matched urine, vaginal and cervical samples; to compare the sensitivity of HR-HPV testing for the detection of CIN2+ in matched samples; and to determine the acceptability of urine testing for cervical screening. DESIGN: Cross-sectional study. SETTING: Secondary care colposcopy clinic in North West England. PARTICIPANTS: Women aged 25 years of age or older, attending colposcopy clinic for management of abnormal cervical screening results or a suspicious-looking cervix. In total, 104 women took part in the study. Triple matched samples were available for 79 and 66 women using Abbott RealTime (ART) and Roche Cobas 4800 (RC), respectively. INTERVENTION: Self-collected urine and vaginal samples and practitioner-obtained cervical samples were tested for HR-HPV by ART and RC assays, including comparison of neat and preservative-fixed urine. Colposcopic opinion was recorded and directed cervical biopsies taken if clinically indicated. The acceptability of self-testing was evaluated by questionnaire. PRIMARY OUTCOME MEASURE: The sensitivity of urine to detect underlying CIN2+. SECONDARY OUTCOME MEASURES: The comparative sensitivity of vaginal and cervical samples to detect CIN2+; the acceptability of urine sampling. RESULTS: Preservative-fixed, but not neat urine, showed good concordance with vaginal samples for the detection of HR-HPV. The sensitivity for detecting CIN2+ was 15/18 (83%) for urine and 16/18 (89%) for cervical and vaginal samples by ART, and 15/17 (88%) for all samples by RC. Urine-based testing was broadly acceptable to women. CONCLUSIONS: Urinary HR-HPV detection offers an alternative strategy of cervical screening. Larger studies to determine its clinical utility are warranted.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/urina , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
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