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2.
Acta Cytol ; 64(1-2): 155-165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30982025

RESUMO

The Papanicolaou (PAP) test is widely used to screen for cervical cancer. All high-grade lesions such as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion, identified on a PAP test should be followed-up by a confirmatory cervical biopsy. In this review, we discuss the challenges in interpreting cervical tissue specimens and the various ancillary techniques used in the evaluation of cervical dysplasia. Ancillary studies include deeper levels, p16 immunohistochemistry (IHC), human papillomavirus (HPV) testing, and, importantly, cyto-histologic correlation. Of these, p16 IHC is consistently sensitive and specific for detecting HSIL. HPV RNA in situ hybridization (ISH) is a newer technique with excellent sensitivity and specificity for detecting virally infected cells and it may be more broadly applicable to both low- and high-grade squamous intraepithelial lesions.


Assuntos
Células Escamosas Atípicas do Colo do Útero/patologia , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Biópsia , Neoplasia Intraepitelial Cervical/diagnóstico , Curetagem , Feminino , Humanos , Teste de Papanicolaou/métodos , Papillomaviridae/fisiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico
3.
BJOG ; 127(3): 377-387, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31631477

RESUMO

OBJECTIVE: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ). DESIGN: Retrospective study. SETTING: Colposcopy clinic. POPULATION: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016. METHODS: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis. MAIN OUTCOME MEASURE: Histologically confirmed CIN 2-3, HR-HPV, margins, age. RESULTS: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001). CONCLUSIONS: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk. TWEETABLE ABSTRACT: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.


Assuntos
Neoplasia Intraepitelial Cervical , Efeitos Adversos de Longa Duração , Margens de Excisão , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Infecções por Papillomavirus , Traquelectomia , Neoplasias do Colo do Útero , Transformação Celular Neoplásica , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Colo do Útero/patologia , Colo do Útero/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Espanha/epidemiologia , Traquelectomia/efeitos adversos , Traquelectomia/métodos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
4.
BJOG ; 127(2): 171-180, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237400

RESUMO

BACKGROUND: Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer. OBJECTIVE: To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862). SEARCH STRATEGY: PubMed, Web of science, Embase and Cochrane database. SELECTION CRITERIA: All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer. DATA COLLECTION AND ANALYSIS: For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals. MAIN RESULTS: Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus. CONCLUSIONS: These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease. TWEETABLE ABSTRACT: This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Lactobacillus/fisiologia , Microbiota/fisiologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Vagina/patologia , Neoplasia Intraepitelial Cervical/microbiologia , Feminino , Humanos , Meta-Análise em Rede , Infecções por Papillomavirus/microbiologia , RNA Ribossômico 16S , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologia , Vagina/microbiologia , Vagina/virologia
5.
J Clin Pathol ; 73(1): 30-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31315894

RESUMO

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , DNA Viral/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Técnicas de Diagnóstico Molecular , Infecções por Roseolovirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Argentina , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/virologia , Feminino , Testes de DNA para Papilomavírus Humano , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/transmissão , Infecções por Roseolovirus/virologia , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Adulto Jovem
6.
BJOG ; 127(1): 58-68, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31541495

RESUMO

OBJECTIVES: To estimate long-term cervical intraepithelial neoplasia grade 3 (CIN3) risks associated with different triage strategies for human papillomavirus positive (HPV+) women with a view to reducing unnecessary referrals. DESIGN: The ARTISTIC trial cohort was recruited in Manchester in 2001-03 and was followed up for CIN3 and cancer notification through national registration until December 2015. RESULTS: The 10-year cumulative risk of CIN3+ was much higher for women with HPV16/18 infection (19.4%, 95% CI 15.8-23.8% with borderline/low-grade cytology and 10.7%, 95% CI 8.3-13.9% with normal cytology) than for those with other HPV types (7.3%, 95% CI 5.4-9.7% with borderline/low-grade cytology and 3.2%, 95% CI 2.2-4.5% with normal cytology). Among the 379 women with normal to low-grade cytology and new HPV infection, the 10-year cumulative CIN3+ risk was 2.9% (95% CI 1.6-5.2%). CONCLUSIONS: The CIN3 risk is confined to women with persistent type-specific HPV so partial genotyping test assays identifying HPV16/18 as a minimum are essential for efficient risk stratification. Immediate referral to colposcopy for HPV+ women with borderline or low-grade cytology and referral after a year if still HPV+ with normal cytology may be unnecessary. Low-grade lesions can safely be retested to identify those with persistent HPV. Recall intervals of 1 year for HPV16/18 and 2 years for other high-risk HPVs are justified for women with normal cytology and might also be considered for women with borderline/low-grade cytology. The minimal risk of invasive cancer that has progressed beyond stage 1A must be weighed against the advantages for patients and the NHS of reducing the number of referrals to colposcopy. TWEETABLE ABSTRACT: Cervical screening would be better for women and cheaper for the NHS if women with HPV and normal to low-grade cytology were retested after a year or two when many infections will have cleared.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Infecções por Papillomavirus/diagnóstico , Triagem , Neoplasias do Colo do Útero/diagnóstico , Adulto , Distribuição por Idade , Idoso , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Detecção Precoce de Câncer , Inglaterra/epidemiologia , Feminino , Seguimentos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
8.
BJOG ; 127(1): 99-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31502397

RESUMO

OBJECTIVE: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure. DESIGN: Prospective cohort study. SETTING: Barcelona, Spain. POPULATION: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP). METHODS: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins. MAIN OUTCOME MEASURE: Treatment failure. RESULTS: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%. CONCLUSION: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients. TWEETABLE ABSTRACT: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Detecção Precoce de Câncer/métodos , Eletrocirurgia , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Adulto , Alphapapillomavirus , Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Colposcopia/estatística & dados numéricos , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Biópsia Guiada por Imagem , Cuidados Intraoperatórios/métodos , Recidiva Local de Neoplasia/virologia , Estudos Prospectivos , Sensibilidade e Especificidade , Falha de Tratamento , Neoplasias do Colo do Útero/virologia
10.
Int J Cancer ; 146(3): 617-626, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861114

RESUMO

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%-0.046%), 0.041% (95% CI: 0.007%-0.076%) and 0.016% (95% CI: 0.000%-0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.


Assuntos
Adenocarcinoma in Situ/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/patologia , California/epidemiologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , Detecção Precoce de Câncer/normas , Feminino , Humanos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Medição de Risco/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
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.
J Exp Ther Oncol ; 13(2): 165-167, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31881134

RESUMO

Objective: Cervical carcinosarcomas (Malignant Mixed Mullerian Tumour [MMMT] ) are very rare neoplasms. Fewer than 100 cases were documented until recently. Because of the rarity, etiologic factors, prognosis and treatment modalities are unclear. A 53 year-old woman presented with postmenauposal vaginal bleeding and abnormal cervical cytology. Cervical biopsy followed by loop electrosurgical excision procedure (LEEP) and cold knife conisation (CKC) was documented as cervical intraepithelial neoplasia III (CIN III). Without follow-up, two years later, the patient was referred with a cervical 6,5 cm mass invading vagina, parametriums and rectum. Biopsy was reported as cervical carcinosarcoma with squmous carcinoma and homologous sarcoma component. Neoadjuvant chemotherapy provided partial response. Subsequently external beam whole pelvis radiotherapy with chemotherapy and brachytherapy was applied. In despite of the treatment, the patient developed sistemic recurrence and died of disease within 10 months. In previous reports most of the patients were in early stage and had better prognosis than uterine carcinosarcomas. Here in we present a case who had a history of high-grade cervical displasia and presented at advanced stage, managed with neoadjuvant chemotherapy and definitive chemoradiotherapy.


Assuntos
Carcinossarcoma , Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Carcinossarcoma/diagnóstico , Conização , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/diagnóstico
13.
Georgian Med News ; (294): 123-128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687963

RESUMO

Microenvironment plays central role in the development of cervical precancerous and cancerous lesions. Cervical intraepithelial neoplasia (CIN) represents a group of precancerous lesions, divided into three degrees. We investigated the distribution of intraepithelial lymphocytes and macrophages in different grades of CIN. We analysed lymphocyte marker CD103, macrophage marker CD68 and proliferation marker Ki67 using standard immunohistochemistry. In addition, we investigated the distribution of lymphocytes using standard haematoxylin and eosin method. The results of our study indicated thatgrade I CIN which subsequently progressed into grade II CIN was characterised with low lymphocytic infiltration, low lympho-epithelial index and low lymphocyte proliferation index. Similar results were seen in cases of CINII which were later progressed into CINIII or in carcinoma. Therefore, we would like to recommend the analysis of microenvironment alterations in CIN lesions, in order to assess their progression potential.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/patologia , Neoplasia Intraepitelial Cervical/patologia , Linfócitos Intraepiteliais/patologia , Antígeno Ki-67/metabolismo , Macrófagos/patologia , Microambiente Tumoral , Neoplasias do Colo do Útero/patologia , Antígenos CD/análise , Neoplasia Intraepitelial Cervical/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/análise , Gradação de Tumores , Neoplasias do Colo do Útero/metabolismo
14.
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
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 666-671, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762235

RESUMO

OBJECTIVE: To explore the dynamic changes of human papillomavirus (HPV) type 16 E5 gene in the development of cervical cancer and the significance of E5 mRNA in early screening of cervical cancer. METHODS: Paraffin specimens of cervical lesions were collected from 49 cases (HPV positive) during September 2015 to December 2017 According to the standard of FIGO, all cervical lesions were diagnosed as: 13 cases of cervicitis, cervical intraepithelial neoplasia disorders (CIN) Ⅰ in 5 cases, CIN Ⅱ in 18 cases, CIN Ⅲ in 5 cases, 8 cases of cervical cancer. Real-time fluorescence quantitative PCR was used to detect the integrity of E5 gene and the mRNA expression levels of E5, E6 and E 7in cervical tissues. RESULTS: All the 49 cases showed positive HPV16 infection. E5 genetic integrity in CINⅠwas higher than that in cervical inflammation, CIN Ⅱand cervical cancer (P < 0.05), which was also higher than that in CIN Ⅲ, but without statistically significance (P>0.05). The mRNA levels of E5, E6, E7 were the highest in CIN Ⅲ. Compared with E6 and E7, E5 presented superior expression in all types of cervical lesions (P < 0.05), while E 6and E7 mRNA expressions only increased in CIN Ⅲ and cervical cancer. CONCLUSION: In the patients with HPV16 infection, the integrity of E5 gene in cervical tissues may be related to the occurrence and development of cervical diseases. E5 gene is expected to be the target gene for early screening of cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Papillomavirus Humano 16 , Humanos , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 701-707, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762241

RESUMO

OBJECTIVE: To investigate the expression level of silencing information regulatory 2 (SIRT2) in cervical cancer and CIN tissues and its clinical significance. METHODS: Immunohistochemistry was carried out to examine the expression of SIRT2 in 262 cases of cervical cancer tissues, 75 cases of precancerous lesions and 75 cases of normal cervical tissues, and the clinical implications of SIRT2 was further analyzed. The protein expression level of SIRT2 in 40 cervical cancer fresh tissue samples and 20 normal cervical tissue samples was detected by Western blot. shRNA-SIRT2 virus was transfected into HeLa cells to obtain the SIRT2-down-regulated HeLa cells. And the influence of down-regulation of SIRT2 on cell proliferation and migration was investigated by MTT and Scratch test. RESULTS: Immunohistochemical results showed that SIRT2 protein expression level gradually increased in cervical cancer, CIN and normal cervix tissues (P < 0.001). Western blot confirmed that SIRT2 expression level was higher in cervical cancer tissues than in normal cervix tissues (P < 0.001). The expression level of SIRT2 in cervical cancer was correlated with some factors, such as lymph node metastasis, histological type, clinical staging and HPV infection (P < 0.05). At the same time, it was independent of some factors including age, differentiation degree, pelvic metastasis, whether involving the cervical interstitial and the involvement depth and whether involving the neck junction and vaginal ends (P>0.05). Mortality in SIRT2 high expression patient group was higher than that of SIRT2 low expression patient group (P < 0.05). shRNA interference technique could effectively inhibit the expression level of SIRT2 in HeLa cells (P < 0.05). MTT assay and Scratch test indicated that down-regulation of SIRT2 expression inhibited the proliferation and migration of HeLa cells (P < 0.05). CONCLUSION: SIRT2 may play a promoting role in the progress of cervical cancer, and SIRT2 may be related to the development of malignant degree of cervical cancer, and the inhibition of SIRT2 expression may be a potential therapeutic target for cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/metabolismo , Sirtuína 2/metabolismo , Neoplasias do Colo do Útero/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Metástase Linfática
17.
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
18.
JAMA ; 322(16): 1570-1579, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31638680

RESUMO

Importance: The World Health Organization recommends cryotherapy or loop electrosurgical excision procedure (LEEP) for histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2 or higher regardless of HIV status. Cryotherapy is more feasible in resource-limited settings but may be less effective for women living with HIV. Objective: To evaluate whether cryotherapy or LEEP is a more effective treatment for high-grade cervical lesions among women with HIV. Design, Setting, and Participants: Single-center randomized trial conducted among women with HIV and CIN grade 2 or 3. From June 2011 to September 2016, women with HIV in Kenya underwent cervical screening with Papanicolaou testing and confirmatory biopsy. The final date on which a study procedure was administered was September 7, 2016. Interventions: Women with HIV infection and CIN grade 2 or 3 were randomized 1:1 to receive cryotherapy (n = 200) or LEEP (n = 200) and were followed up every 6 months for 24 months with a Papanicolaou test and confirmatory biopsy. Main Outcome and Measures: The primary outcome was disease recurrence, defined as CIN grade 2 or higher on cervical biopsy, during the 24-month follow-up period. Results: Among 400 women who were randomized (median age, 37.4 [interquartile range, 31.9-43.8] years), 339 (85%) completed the trial. Over 2 years, 60 women (30%) randomized to cryotherapy had recurrent CIN grade 2 or higher vs 37 (19%) in the LEEP group (relative risk, 1.71 [95% CI, 1.12-2.65]; risk difference, 7.9% [95% CI, 1.9%-14.0%]; P = .01). Adverse events occurred in 40 women (45 events, including change in pathology and death due to other causes) in the cryotherapy group and in 30 women (38 events, including change in pathology and unrelated gynecological complications) in the LEEP group. Conclusions and Relevance: In this single-center study of women with HIV infection and CIN grade 2 or 3, treatment with LEEP compared with cryotherapy resulted in a significantly lower rate of cervical neoplasia recurrence over 24 months. Cost-effectiveness analysis is necessary to determine whether the additional benefit of LEEP represents an efficient use of the additional resources that would be required. Trial Registration: ClinicalTrials.gov Identifier: NCT01298596.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Criocirurgia , Eletrocirurgia , Infecções por HIV/complicações , Neoplasias do Colo do Útero/cirurgia , Adolescente , Adulto , Contagem de Linfócito CD4 , Neoplasia Intraepitelial Cervical/complicações , Neoplasia Intraepitelial Cervical/patologia , Colposcopia , Feminino , Humanos , Incidência , Análise de Intenção de Tratamento , Quênia , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Modelos de Riscos Proporcionais , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Adulto Jovem
19.
Cancer Sci ; 110(12): 3811-3820, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31596999

RESUMO

The Japanese government began a human papillomavirus (HPV) vaccination program for girls aged 12-16 years in 2010 but withdrew its recommendation in 2013 because of potential adverse effects, leading to drastically reduced vaccination uptake. To evaluate population-level effects of HPV vaccination, women younger than 40 years of age newly diagnosed with cervical intraepithelial neoplasia grade 1-3 (CIN1-3), adenocarcinoma in situ (AIS), or invasive cervical cancer (ICC) have been registered at 21 participating institutes each year since 2012. A total of 7709 women were registered during 2012-2017, of which 5045 were HPV genotyped. Declining trends in prevalence of vaccine types HPV16 and HPV18 during a 6-year period were observed in CIN1 (50.0% to 0.0%, Ptrend  < .0001) and CIN2-3/AIS (83.3% to 45.0%, Ptrend  = .07) only among women younger than 25 years of age. Overall, HPV vaccination reduced the proportion of HPV16/18-attributable CIN2-3/AIS from 47.7% to 33.0% (P = .003): from 43.5% to 12.5% as routine vaccination (P = .08) and from 47.8% to 36.7% as catch-up vaccination (P = .04). The HPV16/18 prevalence in CIN2-3/AIS cases was significantly reduced among female individuals who received their first vaccination at age 20 years or younger (P = .02). We could not evaluate vaccination effects on ICC owing to low incidence of ICC among women aged less than 25 years. We found HPV vaccination to be effective in protecting against HPV16/18-positive CIN/AIS in Japan; however, our data did not support catch-up vaccination for women older than 20 years. Older adolescents who skipped routine vaccination due to the government's suspension of its vaccine recommendation could benefit from receiving catch-up vaccination before age 20 years.


Assuntos
Neoplasia Intraepitelial Cervical/virologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/virologia , Vacinação , Adolescente , Criança , Feminino , Humanos , Estudos Prospectivos
20.
J Low Genit Tract Dis ; 23(4): 241-247, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31592970

RESUMO

OBJECTIVE: The aim of the study was to assess whether lower proportions of cervical intraepithelial neoplasia 2+ diagnosed by random biopsy are from lower cut points defining an abnormal colposcopic impression or obtaining only one random biopsy when colposcopic impression is normal. METHODS: We compared colposcopy experiences within Shanxi Province Cervical Cancer Screening Study (SPOCCS) (n = 1,383) and Shenzhen Cervical Cancer Screening Trial (SHENCCAST) (n = 631), which had instructive differences in the cut point defining an abnormal colposcopic impression. RESULTS: The proportion of CIN 2+ diagnosed by random biopsy in SPOCCS (35.0%, 141/403) was higher than SHENCCAST (18.4%, 35/190, p < .001). Quadrant-specific receiver operating characteristic curves for diagnosis of CIN 2+ by colposcopic impression in SPOCCS and SHENCCAST were similar; a lower cut point for an abnormal colposcopic impression in SHENCCAST resulted in lower proportion of CIN 2+ diagnosed by random biopsy. Normal colposcopic impression was found in 85.1% (120/141) of cases of CIN 2+ diagnosed by random biopsy in SPOCCS and in 57.1% (20/35) of such cases in SHENCCAST. Of CIN 2+ diagnosed by random cervical biopsy with normal colposcopic impression, one cervical quadrant was involved with CIN 2+ in 66.7% (80/120) of colposcopies in SPOCCS and 80% (16/20) of colposcopies in SHENCCAST. CONCLUSIONS: Colposcopy series with higher proportions of CIN 2+ diagnosed by random biopsy likely have more stringent cut points defining an abnormal colposcopic impression and have more random biopsies when the colposcopic impression is normal. At colposcopy, we advise multiple biopsies of all acetowhite epithelium or multiple random biopsies to increase the sensitivity of colposcopy.


Assuntos
Biópsia/métodos , Neoplasia Intraepitelial Cervical/diagnóstico , Colposcopia/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colo do Útero/patologia , China , Feminino , Humanos , Sensibilidade e Especificidade
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