RESUMO
OBJECTIVE: To understand the knowledge, preferences, and barriers for self-collected cervical cancer screening (SC-CCS) and follow-up care at the individual and health system level to inform the implementation of community-based SC-CCS. METHODS: Surveys and focus group discussions (FGDs) with women and FGDs with healthcare providers were conducted in Uganda. Survey data were analyzed using frequencies and FGD data were analyzed using thematic content analysis. Data were triangulated between methods. RESULTS: Sixty-four women were surveyed and 58 participated in FGDs. Facilitators to screening access included decentralization, convenience, privacy, confidentiality, knowledge, and education. Barriers to accessing screening included lack of transportation and knowledge, long wait times, difficulty accessing health care, and lack of trust in the health system. Additional implementation challenges included insufficiently trained human resources and lack of infrastructure. CONCLUSION: Integrating SC-CCS within rural health systems in low-resource settings has been under-evaluated. Community-based SC-CSS could prevent high cervical cancer-related mortalities while working within the human and financial resource limitations of rural health systems. SC-CCS is acceptable to women and healthcare providers. By addressing rural women's preferences and barriers to care, decision-makers can build health systems that provide community-centered care close to women's homes across the care continuum.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/prevenção & controle , Cooperação do Paciente , Autocuidado , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , População Rural , Inquéritos e Questionários , Uganda , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem , Displasia do Colo do Útero/diagnósticoRESUMO
BACKGROUND: In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. METHODS: We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012. RESULTS: By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. CONCLUSIONS: To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.
Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Estudos de Coortes , Colposcopia , Feminino , Seguimentos , Humanos , Programas de Rastreamento , Programas Nacionais de Saúde , Gradação de Tumores , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Prognóstico , Escócia/epidemiologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vacinação , Potência de Vacina , Esfregaço Vaginal , Adulto JovemRESUMO
Human pappilomavirus (HPV) has been recognized as the most common sexually transmitted disease in the world and over 100 different HPV types have been identified. Persistent HPV infection has been closely linked to the development of invasive cervical cancer. Although surgical and ablative therapies have been the mainstay of treatment, vaccination against the main oncogenic type of HPV is a reasonable preventive strategy for HPV-induced cervical cancer.
Assuntos
Neoplasias do Colo do Útero/terapia , Feminino , Humanos , Imunoterapia , Estadiamento de Neoplasias , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/uso terapêutico , Fototerapia , Guias de Prática Clínica como Assunto , Prevenção Terciária , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: In vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention. METHODS: Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. RESULTS: Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)]. CONCLUSION: Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4 months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.
Assuntos
Catequina/análogos & derivados , Infecções por Papillomavirus/tratamento farmacológico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Catequina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Efeito Placebo , Chá/química , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologiaRESUMO
DNA from high risk types of human papillomavirus (HPV-HR) is detected in virtually all cervical cancer samples. Most of HPV infections are transient, some persist and lead to development of neoplastics or even cervical cancer lesions. Cervical cancer screening programs are designed to detect early precancerous changes, which should decrease the cancer morbidity and mortality and reduce the costs of diagnosis and treatment. The most effective are screening programs that use cytological and HPV testing. Screening with this method are proven to reduce both the incidence and mortality from cervical cancer WOMEN AGED 21-29 YEARS: HPV testing should not be used to screen women aged 21-29 years, either as a stand-alone test or as a cotest with cytology DNA HPV HR testing in this group of women is recommended in diagnostics ofASCUS. Women DNA HPV positive with ASCUS should be referred to colposcopy WOMEN AGED 30-65 YEARS: Screening by HPV testing alone is not recommended. Women should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years (acceptable). DNA HPV HR /+/, PAP /-/: Two options are recommended. Option 1: 12-months follow-up with contesting (PAP and DNA HPV HR tests). Option 2: Test for HPV16 or HPV16/18 genotypes. If HPV16 or HPV16/18 positive: refer to colposcopy If HPV16 or HPV16/18 negative:12-months follow-up with cotesting. DNA HPV HR /-/, ASC-US: Repetition of cytology in 12 moths is recommended. WOMEN AGED >65 YEARS: No screening is recommended following adequate negative prior to screening. Women with a history of CIN2 or a more severe diagnosis should continue routine screening for at least 20 years. WOMEN HPV VACCINATED: Follow age-specific recommendations (same as unvaccinated women). REQUIREMENTS OF DNA HPV HR TESTS IN CERVICAL SCREENING: The DNA HPV tests used in cervical screening should detect as much as possible of 14 HPV HR types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 i 68) and genotyping HPV 16/18. Candidates' tests should have control of DNA HPV purification and amplification processes and be preserved against contaminations. Clinical sensitivity for CIN 2 + should be no less than 90%. HPV tests and specimen collection system should fulfill the requirements of the act on medical devices.
Assuntos
DNA Viral/isolamento & purificação , Prevenção Primária/normas , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/normas , Adulto , Idoso , Colo do Útero/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Programas Nacionais de Saúde/normas , Polônia , Guias de Prática Clínica como Assunto , Gravidez , Sociedades Médicas/normas , Neoplasias do Colo do Útero/prevenção & controle , Saúde da Mulher , Adulto Jovem , Displasia do Colo do Útero/prevenção & controleRESUMO
OBJECTIVE: To determine whether Curcuma longa Linn extract, NBFR-03, can arrest low-grade squamous intraepithelial neoplasia (LSIL) a 12 week intervention study was performed. METHODS: Of a total of 1473 women undergoing Pap smear screening, 88 cases had LSIL. Only those with persistent LSIL subsequent to antimicrobial therapy, and willing to follow the protocol (N=21), were included for clinical examination, Pap smears, colposcopy, clinical biochemistry, urinalysis and assessment of serum IL-6, being conducted before and after treatment. Standardised NBFR-03 (0.2gm) capsules were administered, twice daily, for 12 weeks. RESULTS: None progressed to higher grade lesion as assessed by Pap smears and colposcopy. Sixteen cases regressed to atypia, ASCUS or inflammatory pattern; 3 persisted as LSIL, 1 discontinued early because of itching, and 1 did not start. None developed any significant abnormality clinically or biochemically. Micrometry showed a significant reduction in nuclear diameter and nucleocytoplasmic ratio after treatment (p<0.02, and <0.05 respectively). Serum IL-6 levels showed a significant decline (mean 248∓ 156 (SEM) vs 27.7∓ 10.5 (SEM) pg/ ml; p<0.05). CONCLUSION: Use of NBFR-03 for 12 weeks was associated with an arrest or regression of LSIL in Pap smears and colposcopy, with reduction in the circulating IL-6 levels.
Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Curcuma/química , Frutas/metabolismo , Interleucina-6/sangue , Extratos Vegetais/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Colposcopia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Teste de Papanicolaou , Prognóstico , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/sangue , Displasia do Colo do Útero/patologiaRESUMO
BACKGROUND: Visual inspection, with acetic acid (VIA) and with Lugol's iodine (VILI), has been demonstrated to have test characteristics comparable to those of Pap smear but are more affordable and easier implement. It also presents an opportunity for management of female genital tract infection. OBJECTIVES: Pilot test integration of cervical cancer screening using visual inspection with genital tract infection identification into an existing MCH-FP in MTRH. METHODS: Cross sectional, descriptive study in which consecutive women were screened for genital tract inflammatory morbidity and cervical cancer through visual inspection. RESULTS: Two hundred and nineteen women with a mean age of 31-3 years, parity of 3.1 were screened. About 54% of study participants had multiple sex partners, 62% had sexual debut earlier than 20 years, while use of tobacco was reported by 4%. The test positivity rate was 13.9% and 16.9% for VIA and VILI respectively. Positive test finding was significantly related to contraceptive never-use after controlling for previous screening (p=0.006).Symptoms of genital tract infections were reported by 38% of the participants with features of cervicitis being reported by nearly 24%. CONCLUSION: Integration of cervical cancer screening and genital tract infection identification and treatment into the existing MCH-FP appears feasible.
Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Doenças dos Genitais Femininos/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Fatores Etários , Criança , Estudos Transversais , Serviços de Planejamento Familiar/organização & administração , Feminino , Doenças dos Genitais Femininos/epidemiologia , Doenças dos Genitais Femininos/prevenção & controle , Humanos , Quênia/epidemiologia , Programas de Rastreamento/estatística & dados numéricos , Centros de Saúde Materno-Infantil/organização & administração , Projetos Piloto , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem , Displasia do Colo do Útero/prevenção & controleRESUMO
OBJECTIVE: To examine the effects of dietary supplements on high-risk human papillomavirus (HPV) infection and cervical carcinogenesis. METHODS: A multi-institutional cross-sectional study was carried out to examine whether dietary supplements were associated with the risk of cervical intraepithelial neoplasia (CIN). We enrolled 1096 women aged 18 to 65 years to participate in an HPV cohort study from March 2006 up to present. For this analysis, we included 328 HPV-positive women (166 controls; 90 CIN I and 72 CIN II/III). The details of each participant's routine dietary intake during the prior year were collected. Specific dietary supplements were classified into 5 categories, namely, multivitamins, multinutrients, vitamin C, calcium, and miscellaneous. RESULTS: A higher HPV viral load was associated with an increased risk of CIN II/III (odds ratio [OR], 3.32; 95% confidence interval [CI], 1.54-7.16; P for trend 0.002). Dietary supplement use including multivitamins (OR, 0.21; 95% CI, 0.09-0.48), vitamins A (OR, 0.19; 95% CI, 0.07-0.53), C (OR, 0.24; 95% CI, 0.10-0.56), E (OR, 0.20; 95% CI, 0.07-0.53), and calcium (OR, 0.21; 95% CI, 0.08-0.50) was significantly associated with a lower risk of CIN II/III. The patients who took multivitamins and had a lower HPV viral load (<15.5 relative light units/positive control) had a significantly decreased frequency of CIN I (OR, 0.35; 95% CI, 0.14-0.87; interaction P = 0.925) and CIN II/III (OR, 0.11; 95% CI, 0.04-0.37; interaction P = 0.304). CONCLUSIONS: The findings of this study suggest that dietary supplements may reduce the risk of CINs in women with high-risk HPV infection.
Assuntos
Suplementos Nutricionais , Infecções por Papillomavirus/prevenção & controle , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Papillomavirus Humano 16/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Infecções por Papillomavirus/etiologia , Infecções por Papillomavirus/patologia , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Carga Viral , Adulto Jovem , Displasia do Colo do Útero/etiologia , Displasia do Colo do Útero/patologiaRESUMO
BACKGROUND: Cervical cancer is the second most common cause of cancer death in women. We have demonstrated previously that zerumbone (ZER) has an anti-cancer effect towards human cervical cancer cells (HeLa). METHODS: Anti-cancer properties of ZER were investigated using female Balb/c mice exposed prenatally to diethylstilboestrol. Female offspring have been treated with ZER (4, 8 and 16 mg/kg), normal saline and cisplatin (10mg/kg; positive control). The anti-cancer properties of ZER were evaluated using histopathology, TdT-mediated dUTP nick end labeling (TUNEL) Assay and immunohistochemical staining of Bcl-2-associated X protein (Bax), a key protein in mitochondrial pathway of apoptosis. In addition, laser capture microdissection microscopy isolated RNA was amplified using reverse transcriptase polymerase chain reaction (RT-PCR) based on the specific primer of B-cell lymphoma 2 (Bcl-2). RESULTS: Treatment with ZER resulted (P<0.05, chi(2) statistics) in the regression of cervical intraepithelial neoplasia (CIN) resembling cisplatin effect (10mg/kg). TUNEL micrographs showed the absence of apoptosis in cancerous tissues treated with normal saline compared to ZER and cisplatin where abundant apoptotic cells were noticed. A post hoc analysis showed a significant (P<0.01) difference in mean percentage of apoptosis between normal saline treatment (0%), ZER (15.7%) and cisplatin (21.7%). Immunohistochemical staining of Bax protein revealed that ZER modulates the expression of this apoptosis marker. Administration of ZER has also modulated the expression of Bcl-2 gene. CONCLUSION: These findings showed that ZER induces apoptosis efficiently in cervical tissues from female Balb/c mice treated prenatally with diethylstilboestrol. This suggested that ZER, a plant-derived compound, could be introduced as a new chemo-preventive agent for CIN in future.
Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Animais , Carcinógenos/toxicidade , Dietilestilbestrol/toxicidade , Feminino , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Mitocôndrias/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias do Colo do Útero/induzido quimicamente , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/induzido quimicamente , Displasia do Colo do Útero/patologiaRESUMO
Disparities related to cervical cancer continue to exist in Mexico, including insufficient screening coverage, problems with quality control and a resulting greater risk of mortality among women from marginalized areas. A lack of opportunities and requirements for continuing education and accreditation of healthcare personnel involved in the screening program is also an issue. HPV DNA testing and HPV vaccines are recent technological innovations that offer a potential solution to the continued negative impact of cervical cancer among Mexican women. This essay attempts to answer questions such as: Why should HPV testing be integrated into the early detection program in Mexico? How can HPV testing best be integrated into the program in Mexico? How-from a public health perspective that seeks to reduce disparities-can HPV vaccination best be implemented in Mexico? HPV testing allows increased positive predictive value while also reducing costly and unnecessary overtreatment of low-grade abnormalities, and HPV vaccines offer the possibility of primary prevention of cervical cancer. The strategy proposed for Mexico includes primary prevention with HPV vaccination for girls aged between 12 and 16 years (before sexual initiation), Pap testing with excellent quality control for women 24-34 years of age and high-risk HPV DNA testing for women 35 years and older. HPV samples would be either clinically collected or self-collected and women with positive HPV test results would receive follow-up high-quality Pap testing. This approach is creative and focuses on reducing disparities and providing high-quality care that is also cost effective.
Assuntos
Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , DNA Viral/análise , Feminino , Humanos , Programas de Rastreamento/métodos , México , Programas Nacionais de Saúde/economia , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/economia , Saúde Pública/economia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/economia , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or Assuntos
Ácido Fólico/metabolismo
, Alimentos Fortificados
, Displasia do Colo do Útero/sangue
, Displasia do Colo do Útero/diagnóstico
, Vitamina B 12/sangue
, Ácido Ascórbico/sangue
, Biópsia
, Carotenoides/sangue
, Feminino
, Seguimentos
, Humanos
, Pré-Menopausa
, Estudos Prospectivos
, Risco
, Tocoferóis/sangue
, Vitamina A/sangue
, Displasia do Colo do Útero/prevenção & controle
RESUMO
This manuscript reviews the current state of knowledge of cervical carcinogenesis and present recent results and introduces ongoing studies on the relationships among micronutrients and natural history of high-risk human papillomaviruses (HR-HPVs) and cervical intraepithelial neoplasia (CIN). Numerous studies have attempted to determine associations between micronutrients and risk of CIN and cervical cancer. Studies that were conducted before a reliable test for assessing HPV infections was available may have resulted in misclassification because of differences in assay sensitivity, which could have led to residual confounding. Another limitation in previous studies may be related to methodologic limitations such as the proper choice of controls for case-control studies. Since cervical cancer does not develop in the absence of HR-HPV infections, only controls exposed to HR-HPV should be included in studies that investigate cofactors for CIN or cervical cancer. Also, the recruitment of subjects for these studies had been based on screening programs that used different approaches such as cytology, colposcopic impression, or biopsy to identify pre-neoplastic cervical lesions. Recent studies have demonstrated that some of these approaches could lead to substantial underdetection and misclassification of preneoplastic lesions of the cervix. Recent studies that addressed these issues have demonstrated that folate is an important micronutrient in cervical cancer prevention via its influence on HR-HPV and the development of CIN. Carefully designed ongoing studies are expected to generate data on whether folate-related biomarkers could be used to identify subjects who are at risk of developing cervical cancer and whether folate supplementation will be beneficial in preventing cervical cancer in women exposed to HR-HPV.
Assuntos
Micronutrientes/farmacologia , Displasia do Colo do Útero/prevenção & controle , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Estados Unidos , Displasia do Colo do Útero/dietoterapia , Displasia do Colo do Útero/etnologiaRESUMO
BACKGROUND: 2006 was an eventful year in the area of screening to prevent cervical cancer. New screening guidelines were introduced nationally in July, and in November the Australian Government agreed to fund one of the human papillomavirus (HPV) vaccines, Gardasil, under the National Immunisation Program. OBJECTIVE: This article discusses the cervical screening program and the Pap test in the era of HPV vaccination. DISCUSSION: With the introduction of a vaccine to prevent the acquisition of significant genital HPV types, many practitioners will be questioning the continuing need for the Pap test. But for those women who have missed out on the vaccine, the Pap test will still play a crucial role in preventing the development of cervical cancer, and the vaccinated cohort will need to continue screening in some form as the vaccine does not cover all the HPV types responsible for anogenital cancer.
Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Adenocarcinoma/epidemiologia , Algoritmos , Austrália/epidemiologia , Colposcopia , Feminino , Humanos , Programas de Rastreamento , Programas Nacionais de Saúde , Neoplasias de Células Escamosas/epidemiologia , Papillomaviridae , Guias de Prática Clínica como Assunto , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/tendências , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: We investigated the effect of folic acid fortification of enriched cereal grains on folate intake in women of predominantly childbearing age at high risk for cervical cancer. METHODS: Subjects in this cross-sectional study were 77 women randomized between November 1999 and December 2000 in the Women's Intervention to Stay Healthy (WISH), a clinical trial evaluating the effect of a tobacco control intervention on the progression of cervical dysplasia. All subjects were cigarette smokers, had a previously abnormal Papanicolaou test, and were positive for high-risk human papillomavirus at entry. Dietary intake was assessed with food-frequency questionnaires completed at the baseline visit for WISH. The effect of folic acid fortification on folate intake was assessed by using pre- and postfortification folate databases to estimate folate intake. RESULTS: Mean folate intake assessed with the postfortification database was 63% higher than intake assessed with the prefortification database: 417 versus 256 microg/d of dietary folate equivalents (P < 0.0001). The proportion of subjects below the estimated average requirement for folate was smaller after fortification than before fortification: 40.3% versus 75.3% (P < 0.0001). Several foods, including white bread, cheese dishes, spaghetti, and rice, became major sources of folate as a result of fortification. CONCLUSIONS: Folic acid fortification resulted in an increased intake of folate in these subjects. However, even with fortification, folate intake in a large proportion of these women remained below recommended levels. These results should be considered before decisions regarding future levels of folic acid fortification are made.
Assuntos
Ácido Fólico/administração & dosagem , Alimentos Fortificados , Fumar/efeitos adversos , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Estudos Transversais , Registros de Dieta , Feminino , Humanos , Pessoa de Meia-Idade , Necessidades Nutricionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Abandono do Hábito de Fumar , Inquéritos e Questionários , Neoplasias do Colo do Útero/etiologia , Displasia do Colo do Útero/etiologiaRESUMO
Many therapies are available for the treatment of human papillomavirus (HPV)-associated disease, particularly external genital warts. However, at present, these therapies aim to remove the lesion rather than specifically target HPV infection. When disease and infection are local, as in cervical intraepithelial neoplasia (CIN), excisional therapies removing lesion and transformation-susceptible cells are highly effective. However, when infection is regional, as is usually the case for the anogenital warts, vulval intraepithelial neoplasia (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia, and vaginal intraepithelial neoplasia, then current treatments are generally inadequate, with high recurrence rates. Future therapies will be directly or indirectly antiviral, targeting HPV protein functions or enhancing the ability of the immune system to resolve infection or inducing apoptosis indirectly in HPV-infected cells. In the short to the medium term, immunotherapies for low-grade disease are the most likely to be in the clinic. Vaccines targeting the E1 and E2 early proteins combined with immunomodulators or conventional adjuvants that induce a strong cell-mediated HPV antigen-specific response and good immune memory would be the predicted combination. Vaccines designed to target high-grade intraepithelial disease, even when used in combination with immunomodulators, are unlikely to effect lesion clearance in more than a fraction of the cases. However, they may have a role as adjunct therapy after cervical conization to prevent the recurrence of CIN or HPV reinfection. They certainly appear to have a role in multifocal disease, such as VIN and AIN, where partial clearance may be effected and lesion size reduced enough for effective ablative or excisional therapy. It seems unlikely that anti-HPV chemotherapies specifically targeting HPV protein functions will be in the clinic in the medium term. However, agents such as indole-3-carbinol have shown efficacy in small clinical trials, and if these effects are confirmed in larger, randomized, placebo-controlled trials, they could be clinically useful.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anticarcinógenos/uso terapêutico , Antivirais/uso terapêutico , Papillomaviridae , Infecções por Papillomavirus/terapia , Infecções Tumorais por Vírus/terapia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/virologia , Vacinas Anticâncer/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Conização , DNA Viral/isolamento & purificação , Feminino , Humanos , Indóis/uso terapêutico , Masculino , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/transmissão , Fotoquimioterapia , Lesões Pré-Cancerosas/terapia , Lesões Pré-Cancerosas/virologia , Retinoides/uso terapêutico , Doenças Virais Sexualmente Transmissíveis/terapia , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/prevenção & controle , Infecções Tumorais por Vírus/transmissão , Neoplasias do Colo do Útero/cirurgia , Vacinas Virais/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
9-Cis-retinoic acid (aliretinoin) is a pan-retinoid receptor agonist and has been demonstrated in preclinical models to have potent chemoprevention effects. The purpose of this study was to determine the utility of using aliretinoin as a chemoprevention agent in cervical dysplasia. Patients with histological evidence of cervical intraepithelial neoplasia (CIN) 2/3 were randomized in a double-blind manner to receive high-dose aliretinoin (50 mg), low-dose of aliretinoin (25 mg), or placebo daily for 12 weeks. Compliance and side effects were monitored at various time points during therapy. At the completion of therapy, all of the patients underwent a loop procedure. Histology of pretreatment biopsies was compared with that of loop specimens. One-hundred and fourteen patients with CIN 2/3 were enrolled in the study. In the 112 patients evaluable for toxicity, headache was the most common clinical side effect and was experienced more frequently (74%) in the high-dose aliretinoin group. Eight patients withdrew from the study before completion of study medication because of unacceptable side effects. In the 104 patients evaluable for efficacy, there was no statistical difference in the rate of regression among the placebo (32%), the low-dose aliretinoin (32%), and the high-dose aliretinoin (36%) groups. (P = not significant; power 0.06). Aliretinoin at these dosages and this schedule does not appear to result in significant regression rates in CIN 2/3 patients when compared with placebo. Headache is encountered frequently and may thwart efforts to increase the dose or duration of aliretinoin in future cervical cancer chemoprevention studies. The rate of histological regression in biopsied CIN 2/3 patients is high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size in cervical dysplasia chemoprevention studies.
Assuntos
Antineoplásicos/uso terapêutico , Quimioprevenção , Tretinoína/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Adolescente , Adulto , Alabama , Alitretinoína , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Avaliação de Medicamentos , Feminino , Hemoglobinas/efeitos dos fármacos , Humanos , Cooperação do Paciente , Índice de Gravidade de Doença , Resultado do Tratamento , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Triglicerídeos/sangue , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Saúde da MulherRESUMO
Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical intraepithelial neoplasia (CIN) and cancer. A newly designed vaccine, comprising the HPV16 L2, E6 and E7 as a single fusion protein (TA-CIN), was shown to elicit HPV16-specific CTL, T-helper cells and antibodies in a pre-clinical mouse model. These immune responses effectively prevented outgrowth of HPV16-positive tumour cells in a prophylactic setting as well as in a minimal residual disease setting. CTL immunity was optimally induced when TA-CIN was employed in heterologous prime-boost regimens in combination with TA-HPV, a clinical grade vaccinia-based vaccine. These data provide a scientific basis for the use of TA-CIN, alone or in combination with TA-HPV in future human trials.
Assuntos
Vacinas Anticâncer/toxicidade , Proteínas do Capsídeo , Capsídeo/toxicidade , Proteínas Oncogênicas Virais/toxicidade , Papillomaviridae/imunologia , Proteínas Recombinantes de Fusão/toxicidade , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/uso terapêutico , Antígenos de Neoplasias/toxicidade , Antígenos Virais/administração & dosagem , Antígenos Virais/imunologia , Antígenos Virais/uso terapêutico , Antígenos Virais/toxicidade , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Capsídeo/administração & dosagem , Capsídeo/imunologia , Capsídeo/uso terapêutico , Linhagem Celular , Linhagem Celular Transformada , Avaliação Pré-Clínica de Medicamentos , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas Virais/administração & dosagem , Proteínas Oncogênicas Virais/imunologia , Proteínas Oncogênicas Virais/uso terapêutico , Proteínas E7 de Papillomavirus , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Vacinas Acelulares/administração & dosagem , Vacinas Acelulares/imunologia , Vacinas Acelulares/uso terapêutico , Vacinas Acelulares/toxicidade , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/terapia , Displasia do Colo do Útero/virologiaRESUMO
Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.