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1.
Medicine (Baltimore) ; 99(9): e19273, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118737

RESUMO

A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV), progress rapidly to cervical disease. We characterized HPV genotypes within cervical tumor biopsies, assessed the relationships of cervical disease stage with age, HIV-1 status, absolute CD4 count, and CD4 percentage, and identified the predictive power of these variables for cervical disease stage in a cohort of South African women.We recruited 181 women who were histologically diagnosed with cervical disease; 87 were HIV-1-positive and 94 were HIV-1-seronegative. Colposcopy-directed tumor biopsies were confirmed by histology and used for genomic DNA extraction. The Roche Linear Array HPV genotyping test was used for HPV genotyping. Peripheral whole blood was used for HIV-1 rapid testing. Fully automated FC500MPL/CellMek with PanLeucogate (PLG) was used to determine absolute CD4 count, CD4 percentage, and CD45 count. Chi-squared test, a logistic regression model, parametric Pearson correlation, and ROC curves were used for statistical analyses. We used the Benjamini-Horchberg test to control for false discovery rate (FDR, q-value). All tests were significant when both P and q were <.05.Age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (P < .0001, q < 0.0001) and HIV-1-positive women (P = .0003, q = 0.0003). Sixty eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with a CD4 percentage equal or less than 28%, and a median absolute CD4 count of 400 cells/µl (IQR 300-500 cells/µl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells vs 25% (10/40) who possessed >28% CD4 cells (both P < .001, q < 0.001). Furthermore, 70% (28/40) of women with ICC possessed CD4 count >350 compared to 30% (12/40) who possessed CD4 count ≤ 350 (both P < .001, q < 0.001).Age is an independent predictor for ICC. In turn, development of ICC in HIV-1-positive women is independent of the host CD4 cells and associates with low CD4 percentage regardless of absolute CD4 count that falls within the normal range. Thus, using CD4 percentage may add a better prognostic indicator of cervical disease stage than absolute CD4 count alone.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por HIV , HIV-1 , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Neoplasia Intraepitelial Cervical/sangue , Neoplasia Intraepitelial Cervical/virologia , Estudos de Coortes , Feminino , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/virologia , Fatores de Risco , África do Sul/epidemiologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/virologia
2.
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
3.
Int J Cancer ; 146(7): 1810-1818, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31245842

RESUMO

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.


Assuntos
Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Adulto , Idoso , Colúmbia Britânica/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/etiologia , DNA Viral , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Vigilância em Saúde Pública , Neoplasias do Colo do Útero/diagnóstico
4.
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
5.
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
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
7.
Gynecol Oncol ; 155(3): 436-443, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31604662

RESUMO

OBJECTIVE: Human papillomavirus (HPV) 16/18 genotyping is an effective method for triage of high-risk (hr) HPV-positive women in primary hrHPV screening for cervical cancer. The present study aimed to evaluate whether co-infected with other hrHPV types will affect the risk of cervical carcinogenesis in HPV16/18 positive women. METHODS: A total of 313,704 women aged ≥30 years were screened in China. Among them, 4,933 HPV16/18-positive participants underwent colposcopy-directed biopsy. The HPV genotypes were identified using the Cobas HPV genotyping system. Multinomial logistic regression was used to model different HPV16/18 infection patterns. RESULTS: The overall prevalence rates of hrHPV and HPV16/18 were 7.85% (24,456/311,382) and 1.95% (6,086/311,382) respectively. Among HPV16/18 positive individuals, 33.24% (2,023/6,086) were co-infection with multiple types. Of the 4933 women who underwent colposcopy, their HPV16/18 infection patterns were as follows: 52.38% (2,584/4,933) HVP16 only, 23.54% (1,161/4,933) HPV16 + other hrHPVs, 14.98% (739/4,933) HPV18 only, 6.83% (337/4,933) HPV18 + other hrHPVs, 1.13% (56/4,933) HPV16 + 18, 1.13% (56/4,933) HPV16 + 18+other hrHPVs. After adjusting for cofactors, compared with single HPV16 infection, the risk of developing cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+) was significantly lower in HPV16 + other hrHPVs group (odds ratio [OR] = 0.637, 95% confidence interval [CI] = 0.493-0.822). CONCLUSION: HPV16/18 co-infection with other hrHPVs is a common phenomenon. Different HPV16/18 infection patterns may influence the risk of cervical carcinogenesis. HPV16 co-infected with other hrHPVs appears to have a lower associated risk of CIN3+ in ≥30 years old women.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Carcinogênese , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Coinfecção/epidemiologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/virologia
8.
Asian Pac J Cancer Prev ; 20(9): 2579-2582, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31554348

RESUMO

Objectives: The objectives of the study are to assess the prevalence of colposcopic and histological abnormalities in patients diagnosed with ASCUS and ASC-H and to compare the prevalence of CIN in each group. Methods: Population-based cross-sectional retrospective study was conducted in one of tertiary hospitals in UAE. All cervical smears reported as ASCUS or ASC-H in 2015 were included in this study. The local guideline in 2015 was to refer all cases of ASC for colposcopy assessment. Results: Overall 7,418 cervical smears were processed at our laboratory service, 5.6% (n=413) were reported as ASC. 95% of them (n=394) were ASCUS and 5% (n=19) were ASC-H. The overall prevalence of high grade CIN in patients with ASC-H is 26% compared with 0.8% for patients with ASCUS regardless the age. The relative risk of patients with ASC-H is 8 folds higher than patients with ASCUS to have low grade CIN but 29 fold higher risk of having High grade CIN and the P value =0.0001.Conclusion: ASC-H cytology confers a substantially higher risk for high grade CIN than ASCUS regardless of age. HPV test is an important triage test in patients with ASCUS to predict cellular changes and CIN.


Assuntos
Células Escamosas Atípicas do Colo do Útero/patologia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/epidemiologia , Colposcopia/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/métodos , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Triagem , Emirados Árabes Unidos/epidemiologia
9.
Mymensingh Med J ; 28(3): 655-661, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31391440

RESUMO

This cross-sectional and population based study was carried out in four randomly selected Upazila of four districts of Dhaka division by the department of Obstetrics and Gynaecology of Dhaka Medical College Hospital (DMCH) and Bangabandhu Sheikh Mujib University (BSMMU), Dhaka, Bangladesh from October 2014 to March 2015 to detect the prevalence of Cervical Intraepithelial Neoplasia (CIN) among women in four Upazila of Dhaka division of Bangladesh. Married women ages between 25-55 years, mentally able to provide informed consent were recruited. Women with chronic illness, pregnancy and women with previous treatment for CIN were excluded from the study. During 6 months of study period, a total 1165 cases were examined. Most of the attendants were between 30-35 years. Muslim participants were more than Hindus (95.27% vs. 4.37%) and 0.34% attendants were from Christian religion. Among the participants majority (42.37%) of them were up to primary level. Most (98.45%) of the women were house wife and most (54.5%) of them had monthly family income between Tk. 5001-10000. It was observed that 6.5% of their husband had 2 wives and 1.2% had 3 wives. Regarding their living status, 90.6% were living together, 8.6% of their husband was living at their work place & 0.7% was living abroad. About 30.4% of their husbands were farmer others were businessman, unemployed, driver and other service holder. It was found that 67(5.8%) out of 1165 cases were diagnosed as VIA +ve cases. Among 1165 cases 94.2% were normal, 4.7% were diagnosed as CIN I, 1% were CIN II and none of them was CIN III. Colposcopy guided punch biopsy were taken from all CIN cases and found that among 67 cases of colposcopically diagnosed CIN, histopathologically 28(2.4%) cases were diagnosed as normal, 32(2.7%) cases were CIN I, 4(0.3%) cases were CIN II & 3 (0.3%) cases were CIN III. In this study, crude prevalence of CIN I, CIN II and CIN III were 2.7%, 0.3% and 0.3% respectively. This study provides the first population-based prevalence of CIN in Bangladesh which will guide the Government of Bangladesh to upgrade the activities of already existing cervical cancer screening programme.


Assuntos
Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Adulto , Bangladesh/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Prevalência , Neoplasias do Colo do Útero/epidemiologia
10.
Asian Pac J Cancer Prev ; 20(8): 2409-2413, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450914

RESUMO

Background: WHO has recommended Visual Inspection with Acetic acid (VIA) or Human Papillomavirus (HPV) DNA testing if feasible, for cervical cancer screening in low income countries. However, the number of women undergoing screening is very low as a result of limited information, inadequate infrastructure and invasive nature of sampling. Methods: A cross sectional study was carried out comparing HPV DNA detection by Polymerase Chain Reaction (PCR) in paired cervical and urine samples procured from histologically confirmed cervical cancer cases. Results: Amongst the samples collected from 114 cervical cancer cases, HPV DNA was tested positive in cervical samples of 89 (78.1%) and urine samples of 55 (48.2%) patients. The agreement between the two sampling methods was 66.7% and the kappa value was 0.35 indicating a fair agreement. The sensitivity of HPV detection using urine samples was 59.6% (95% confidence interval 49.16%-69.15%) and the specificity was 92% (95% confidence interval 75.0%-97.8%). Conclusion: Even though not acceptable as an HPV DNA screening tool due to low sensitivity, the urine sampling method is inexpensive and more socially acceptable for large epidemiological surveys in developing countries to estimate the burden.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , DNA Viral/urina , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Manejo de Espécimes/métodos , Urinálise/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Estudos Transversais , Países em Desenvolvimento , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
11.
Int J Gynaecol Obstet ; 147(1): 43-48, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31272132

RESUMO

OBJECTIVE: To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology. METHODS: A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24 months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline. The outcome was regression, persistence, or progression of CIN2. RESULTS: Overall, 93 women aged 18-56 years were enrolled. Spontaneous regression was observed for 61 (66%) women, and 21 (23%) progressed to CIN3. Eight (9%) women had chlamydia seropositivity at baseline. Multivariate analysis showed that anti-chlamydia IgG seropositivity (odds ratio [OR], 19.1; 95% confidence interval [CI], 1.9-189.7), previous high-grade squamous intraepithelial lesion cytology (OR, 5.0; 95% CI, 1.7-14.6), and HPV16 (OR, 4.8; 95% CI, 1.7-13.7) increased the risk of CIN2 persistence or progression. CONCLUSION: Women with CIN2 and chlamydia IgG seropositivity had increased risk of progression to CIN2+ and immediate treatment may be recommended for these women. Larger clinical studies are needed to confirm the results, but chlamydia serology might be introduced into CIN2 management to better individualize treatment.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Infecções por Chlamydia/sangue , Neoplasias do Colo do Útero/patologia , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/terapia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Tratamento Conservador , Progressão da Doença , Feminino , Humanos , Imunoglobulina G/sangue , Infecções por Papillomavirus/diagnóstico , Estudos Prospectivos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia
12.
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
13.
Diagn Cytopathol ; 47(10): 1028-1036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359607

RESUMO

BACKGROUND: The cytology diagnosis of glandular cell abnormalities (GCAs) is diagnostically challenging, causing inadequate reproducibility. Histological outcome of GCA on cytology varies from benign to malignant diseases. The goal of this study is to evaluate histological outcome and identify distinctive cohorts of patients with GCA based on human papillomavirus (HPV) status, age, and associated squamous abnormality to stratify the patient into high risk for squamous/glandular lesions. METHODS: From 2012 to 2017, out of 162 088 ThinPrep Papanicolaou tests performed, 998 (0.61%) were reported as GCAs. Histologic follow-up was available in 638 cases and 429 had concurrent HPV results. RESULTS: The overall rate of high-risk human papillomavirus (hrHPV)-positivity (hrHPV+) was 33.6% (144/429 cases). Among the hrHPV+ cases, 18.1% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 3.5% squamous cell carcinoma (SCC), 3.5% cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 2.8% endometrial carcinoma. Among hrHPV- cases, 1.4% had CIN2/3, 1.1% AIS/ADC, and 17.5% endometrial carcinoma. The high-grade cervical lesions (CIN2/3/AIS/ADC) were significantly higher in women with hrHPV+ and associated squamous abnormalities compared to hrHPV- and no squamous abnormality in all age groups except patients >65 years. Endometrial carcinoma was most commonly present in women >65 years especially with HPV- and no associated squamous abnormalities. CONCLUSIONS: HPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with GCA especially with associated squamous abnormalities on cytology. The endometrial carcinoma is more frequent in hrHPV- older women. The combination of cytology with knowledge of associated squamous abnormality, hrHPV status, and age can significantly aid in stratifying the patient into high risk for glandular/squamous lesions which facilitates appropriate management of these patients.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Células Epiteliais/patologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Células Epiteliais/virologia , Feminino , Testes de DNA para Papilomavírus Humano/normas , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou/normas , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
15.
Asian Pac J Cancer Prev ; 20(7): 2059-2064, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350966

RESUMO

Background/Objective: Cervical cancer ranks the second among the most common gynecologic cancers. This study was established to determine the distribution of cervical HPV genotypes among different Pap readings in Duhok/Iraq. Methods: Between January and September-2016, HPV-DNA was tested in 64 women. Genotyping was carried out by the hybridization reverse blot technique. Cervical smears were taken, performed by ThinPrep technique and stained by Pap stain. Results: Twenty six (40.6%) cases were positive for HPV, 12 (46.2%) in normal and 14 (53.8%) in abnormal Pap smears. 39 (19 high-risk and 16 low-risk) genotypes were identified. The high risk group comprised 6 HPV16, 4 HPV18, 2 HPV66, 2 HPV52, 2 HPV39, 1 HPV56, 1 HPV31 and 1 HPV45. The 16 low risk strains encompassed 4 HPV6 strains, 4 HPV71, 2 HPV54 and 2 HPV83, HPV11, HPV61 HPV84, and HPV62. Mixed infections were described in 4 women (6.25%), limited to the NILM, ASC-US and LSIL smears. They included variable admixtures of 7 high risk genotypes, HPV39 (both copies), HPV66 (both copies), HPV52, HPV31, HPV45 and 6 low risk strains: HPV83, HPV6, HPV11, HPV54, HPV62 and HPV71. Conclusions: The higher frequency of HR-HPV than the LR-HPV with identification of 4 mixed cases indicates that our women are at risk of developing cervical cancer. Detection of HR-HPV in NILM and ASC-US smears with restriction of some strains to these 2 categories highlights the great value of HPV genotyping as a surrogate test to pick up unscreened women at risk of developing cervical malignancy particularly when a proper screening program is absent.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Programas de Rastreamento/métodos , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/classificação , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/genética , Feminino , Seguimentos , Genótipo , Humanos , Iraque/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto Jovem
16.
Asian Pac J Cancer Prev ; 20(7): 2139-2143, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350977

RESUMO

Background: To compare the cytomorphological features of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) observed in a liquid-based Pap smear with the histopathological features observed in a concurrent colposcopic biopsy specimen obtained immediately after obtaining the Pap smear. Methods: Cytomorphological features such as cytoplasmic differentiation, nuclear/cytoplasm (N/C) ratio, chromatin pattern, thickening of nuclear contour, and the appearance of the nucleolus of 247 ASC-H obtained from 25 liquid-based Pap smear ASC-H cases were compared with those of the cells obtained from biopsied samples. Human papillomavirus (HPV) infection was tested for 39 HPV genotypes using Uniplex E6/E7 polymerase chain reaction method. Results: Of the 25 ASC-H cases, 22 (88%) showed cervical intraepithelial neoplasia grade 1 or greater (CIN1+) and 3 (12%) were benign. HPV infection was detected in 100% CIN1+ cases and 66.7% benign cases. Significant differences such as marked hyperchromasia, thickened nuclear contour, and prominent nucleoli were observed between ASC-H cases with CIN1+ and the benign cases. Conclusion: The presence of small dysplastic cells displaying marked hyperchromasia, thickening of nuclear contour, and prominent nucleoli on Pap smear strongly suggest the presence of CIN in ASC-H cases.


Assuntos
Células Escamosas Atípicas do Colo do Útero/patologia , Neoplasia Intraepitelial Cervical/patologia , Colposcopia/métodos , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Adulto , Células Escamosas Atípicas do Colo do Útero/virologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/virologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Prognóstico , Manejo de Espécimes , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
17.
BJOG ; 126(11): 1365-1371, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356722

RESUMO

OBJECTIVE: To assess the 5-year risk of high-grade lesions in women with a transient high-risk HPV infection. DESIGN: Population-based cohort study. SETTING: HPV primary testing within population-based organised cervical cancer screening programmes. POPULATION: Italian women enrolled in seven pilot projects and attending the second round. METHODS: On the basis of the cytology triage performed on HPV-positive women, immediate colposcopy or HPV repeat at 12 months was recommended. Data were collected at the subsequent round 3-4 years after HPV infection clearance. MAIN OUTCOME MEASURES: Rates of HPV infection, CIN2+ and CIN3+ detection at subsequent round after HPV clearance, and relative risks (RR) in comparison with HPV-negative women (with 95% confidence interval). RESULTS: Data on 1230 women (1027 aged 25-64 years and 203 aged 35-64 years) have been analysed. Overall compliance with repeat HPV testing was 84%. In comparison with HPV-negative women, those with a transient HPV infection had higher proportions of HPV positivity (15% versus 3.7%) and of CIN2+ lesions (0.87% versus 0.23%) in round two; most of these (7/10) were CIN2; no cancers were detected, and CIN3 occurred in 3/1230 (0.24%). CONCLUSIONS: HPV-based protocols for cervical cancer screening allow long intervals for HPV-negative women; it is important to monitor the clinical outcome in the women with transient high-risk HPV infection. CIN3 detection is similar to that observed in routine European cytology-based screening programmes (CIN3+: 2.7‰); 5-year intervals may provide reasonable protection but longer intervals are not recommended. TWEETABLE ABSTRACT: A screening interval of 5 years (but no longer) appears safe in women with transient HPV detection.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Detecção Precoce de Câncer , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Neoplasia Intraepitelial Cervical/epidemiologia , Estudos de Coortes , Colposcopia , Feminino , Humanos , Itália/epidemiologia , Metanálise como Assunto , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Projetos Piloto , Medição de Risco , Fatores de Tempo , Neoplasias do Colo do Útero/epidemiologia
18.
Gynecol Oncol ; 154(2): 368-373, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31182225

RESUMO

OBJECTIVE: This study evaluates the long-term risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV positive women triaged with FAM19A4/miR124-2 methylation analysis. METHODS: In a post hoc analysis, data on FAM19A4/miR124-2 methylation, cytology, and HPV16/18 genotyping of HPV positive women (n = 1025) from a large population-based screening cohort with 14-year follow-up were evaluated. Cumulative CIN3+ incidences over 3 screening rounds (5-year intervals) of 4 triage strategies were compared: FAM19A4/miR124-2 methylation analysis, cytology, HPV16/18 genotyping with FAM19A4/miR124-2 methylation, and HPV16/18 genotyping with cytology. RESULTS: Kaplan-Meier estimates of 14-year cumulative CIN3+ incidence of HPV positive women with a negative methylation and a negative cytology triage test were comparable (16.3% and 15.6%, respectively). The cumulative CIN3+ incidence of methylation positive and cytology positive women were 39.8% and 46.5%, respectively. HPV16/18 genotyping with methylation and HPV16/18 genotyping with cytology resulted in the lowest 14-year cumulative CIN3+ incidence among triage negative women (10.7% and 10.0%, respectively), but cumulative CIN3+ incidence among triage positive women was lower (33.4% and 35.7%, respectively) compared with triage by methylation alone and cytology alone. CONCLUSIONS: Among HPV positive women of 30 years and older, a negative FAM19A4/miR124-2 methylation triage test provides a similar long-term CIN3+ risk compared with a negative cytology triage test. Because of their high CIN3+ risk, women with a positive methylation triage test could be referred for colposcopy. Therefore, FAM19A4/miR124-2 methylation analysis is a promising alternative to cytology for triage of HPV positive women.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Citocinas/isolamento & purificação , Neoplasias do Colo do Útero/genética , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/classificação , Neoplasia Intraepitelial Cervical/epidemiologia , Metilação de DNA , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/isolamento & purificação , Infecções por Papillomavirus/genética , Valor Preditivo dos Testes , Medição de Risco , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/epidemiologia
19.
Gulf J Oncolog ; 1(30): 52-56, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31242982

RESUMO

OBJECTIVE: To determine the incidence and the association between atypical glandular cells (AGC) reported on cervical pap smears and the underlying malignant and pre-malignant genital tract pathology. METHODS: A retrospective study was performed on the files of women who were had attended our colposcopy clinic at King Hussein Medical Centre (KHMC), between April 2014 and April 2018. Out of 8483 cervical pap smears reviewed, 68 patients have smears reported to be atypical glandular cells of undetermined significance (AGUS). Proper evaluation and follow up was available for 62 patients by performing colposcopic examination, repeating pap smear, proper biopsies and histological results. The factors considered included patients age, parity, symptoms, presence of pregnancy, smoking habits, hormonal therapy usage, colposcopic finding, and histological results of biopsies performed. Data were analyzed and comparison was performed between malignant and pre-malignant lesions. RESULTS: 68 cases of AGUS pap smears were identified out of 8483 cases reviewed forming incidence of about (0.8%). Of 62 patients with AGUS pap smears, twenty-two cases (32.3%) were found to have clinically significant malignant lesions on subsequent histological follow up. It included 12 cases of endometrial adenocarcinoma, 5 cases of adenocarcinoma of cervix, 3 cases of squamous cell carcinoma of cervix and 2 cases with secondary metastasis to vagina. Of the 62 patients with AGUS pap smears, fourteen cases (20.6%) were found to have pre-malignant lesions. This included 7 cases of endometrial hyperplasia, 3 cases of adenocarcinoma in situ of cervix (ACIS) and 4 cases with cervical squamous intra-epithelial lesions. Abnormal vaginal bleeding was the most common presenting symptom (30.6%); Woman above the age of 40 years and especially post-menopausal were more likely to have significant histological abnormalities. CONCLUSION: Though the incidence of AGUS is low, it still important and clinically significant due to high substantial risk of having underlying premalignant or malignant lesions. Colposcopy and directed biopsy, endo-cervical curettage and endometrial biopsy should be performed to all women with AGUC especially to those above the age of 40 years, menopause, or having abnormal vaginal bleeding.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasia Intraepitelial Cervical/epidemiologia , Colo do Útero/patologia , Lesões Pré-Cancerosas/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/estatística & dados numéricos , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/patologia , Feminino , Seguimentos , Humanos , Incidência , Jordânia/epidemiologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Prognóstico , Estudos Retrospectivos , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia
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