RESUMEN
Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem.
Asunto(s)
Infecciones por VIH/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer , Femenino , Humanos , Huésped Inmunocomprometido , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Lesiones Precancerosas/terapia , Prevención Primaria , Prevención SecundariaRESUMEN
BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Alphapapillomavirus , Infecciones por VIH , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adolescente , Adulto , Detección Precoz del Cáncer , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Tamizaje Masivo/métodos , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/terapiaRESUMEN
We conducted a meta-analysis of test agreement/concordance between human papillomavirus (HPV) testing in self-collected vs clinician-collected samples in 26 studies (10 071 participants) updating a previous meta-analysis on accuracy for cervical precancer. Pooled overall agreement was 88.7% (95% CI: 86.3%-90.9%), positive agreement was 84.6% (95% CI: 79.9%-88.7%), negative agreement was 91.7% (95% CI: 89.1%-94.0%) and kappa was 0.72 (95% CI: 0.66-0.78). Subgroup meta-analyses suggested higher overall agreement for target amplification-based DNA assays (90.4%) compared to signal amplification-based DNA assays (86.7%; P = .175) or RNA assays (82.3%; P < .001). HPV test agreement/concordance targets may provide criteria to extend existing validations toward alternative sampling approaches and devices/storage media.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Alphapapillomavirus/genética , ADN , ADN Viral/análisis , ADN Viral/genética , Detección Precoz del Cáncer , Femenino , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Sensibilidad y Especificidad , Manejo de Especímenes , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
There is limited access to effective cervical cancer screening programs in many resource-limited settings, resulting in continued high cervical cancer burden. Human papillomavirus (HPV) testing is increasingly recognized to be the preferable primary screening approach if affordable due to superior long-term reassurance when negative and adaptability to self-sampling. Visual inspection with acetic acid (VIA) is an inexpensive but subjective and inaccurate method widely used in resource-limited settings, either for primary screening or for triage of HPV-positive individuals. A deep learning (DL)-based automated visual evaluation (AVE) of cervical images has been developed to help improve the accuracy and reproducibility of VIA as assistive technology. However, like any new clinical technology, rigorous evaluation and proof of clinical effectiveness are required before AVE is implemented widely. In the current article, we outline essential clinical and technical considerations involved in building a validated DL-based AVE tool for broad use as a clinical test.
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Aprendizaje Profundo , Detección Precoz del Cáncer/métodos , Neoplasias del Cuello Uterino/diagnóstico , Algoritmos , Femenino , Humanos , Papillomaviridae/aislamiento & purificación , Reproducibilidad de los Resultados , Neoplasias del Cuello Uterino/virologíaRESUMEN
BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.
Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Infecciones por Papillomavirus/inmunología , Linfocitos T/inmunología , Neoplasias del Cuello Uterino/inmunología , Carcinogénesis/inmunología , Carcinogénesis/patología , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/patología , Linfocitos T/patología , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. METHODS: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. DISCUSSION: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.
Asunto(s)
Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/inmunología , Anticuerpos Antivirales , Niño , Femenino , Humanos , Esquemas de Inmunización , Inmunogenicidad Vacunal , Masculino , Infecciones por Papillomavirus/inmunología , Vacunas contra Papillomavirus/uso terapéutico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: We evaluated acceptability of cervico-vaginal self-collection (CVSC) and prevalence of human papillomavirus (HPV) in Human immunodeficiency virus (HIV)-infected and HIV-uninfected women living in the Tapajós region, Amazon, Brazil. METHODS: Cross-sectional study recruited 153 non-indigenous women (HIV-uninfected, nâ¯=â¯112 and HIV-infected, nâ¯=â¯41) who voluntarily sought assistance in health services. Peripheral blood for HIV screening and cervical scraping (CS) for HPV detection were collected. Women who accepted to perform CVSC received instructions and individual collection kits. Risk factors for high-risk HPV genotypes (hrHPV) were identified by uni- and multivariate analyses. RESULTS: The overall acceptability of CVSC was 87%. Only HIV-infected women had cytological abnormalities (12.2%). Prevalence of any HPV and hrHPV infection was 42.9% and 47.9% for HIV-uninfected and 97.6% and 77.5% for HIV-infected women, respectively. There was significant agreement in the detection of HPV (88%, 0.76, 95% confidence interval [CI], 0.65-0.87) and hrHPV (79.7%, 0.56, 95% CI, 0.41-0.71) between self-collected and clinician-collected samples. The most prevalent hrHPV types were HPV16 and HPV18 in HIV-uninfected and HPV16, HPV51 and HPV59 in HIV-infected women. HIV-infected women with hrHPV infection had multiple hrHPV infections (pâ¯=â¯0.005) and lower CD4 count (pâ¯=â¯0.018). Risk factors for hrHPV infection included being HIV-infected and having five or more sexual partners. CONCLUSIONS: CVSC had high acceptability and high prevalence of hrHPV types in women living in the Tapajós region, Amazon, Brazil.
Asunto(s)
Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Anciano , Brasil/epidemiología , Recuento de Linfocito CD4 , Cuello del Útero/patología , Cuello del Útero/virología , Estudios Transversales , ADN Viral/aislamiento & purificación , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Infecciones por VIH/virología , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Prevalencia , Factores de Riesgo , Manejo de Especímenes/métodos , Manejo de Especímenes/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Vagina/patología , Vagina/virología , Adulto JovenRESUMEN
Literature published between 1975 and 2015 was systematically reviewed to conduct a case-comparator study of tissue based, immunohistochemical biomarker expression among malignant glandular histotypes of the uterine cervix so as to identify differences that could have diagnostic utility. Of the 902 abstracts, 154 articles had a full review, and 52 were included. Biomarker positivity in cases of adenocarcinoma in situ (AIS) were compared with atypical lobular endocervical glandular hyperplasia and invasive histotypes grouped as mucinous, endometrioid, adenosquamous, serous clear cell, minimal deviation-gastric type, and mesonephric carcinomas (7 AIS case-comparators). The invasive histotypes were compared with each other (30 adenocarcinoma case-comparators). Biomarker positivity in all 37 case-comparators was calculated as weighted averages of histotype-specific estimates. Unsupervised hierarchical clustering examined differences in expression and were visualized via heatmaps and dendrograms. Of the 56 biomarkers tested, 1 or more of 15 showed a 50% or more difference in positive expression in 6 (86%) of the AIS and 21 (70%) of the adenocarcinoma case-comparators. There was no data on the comparison of serous clear cell to mesonephric carcinoma. AIS case-comparator biomarkers were HIK1083, alpha SMA, PAX8, VIL1, CEA, p53, p16, and CD10, and only alpha SMA had a difference of 100%. The adenocarcinoma case-comparator biomarkers were CEA, p53, Claudin18, HIK1083, p16, Calretinin, CD10, PR, Chromogranin, MUC6, Vimentin and p63, and none had a difference of 100%. Biomarker expression in the discrimination of AIS from invasive adenocarcinoma, and the invasive histotypes from each other is understudied. One or more of 15 biomarkers could have diagnostic utility.
Asunto(s)
Adenocarcinoma in Situ/metabolismo , Biomarcadores/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma in Situ/patología , Cuello del Útero/metabolismo , Cuello del Útero/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Glandulares y Epiteliales/patología , Neoplasias del Cuello Uterino/patologíaRESUMEN
Multiple epidemiological studies have documented an association between metformin, used for treatment of type 2 diabetes, and reduced cancer incidence and mortality. Cell line models may not accurately reflect the effects of metformin in the clinical setting. Moreover, findings from animal model studies have been inconsistent, whilst those from more recent epidemiological studies have tempered the overall effect size. The purpose of this review is to examine metformin's chemopreventive potential by outlining relevant mechanisms of action, the most recent epidemiologic evidence, and recently completed and ongoing clinical trials. Although repurposing drugs with excellent safety profiles is an appealing strategy for cancer prevention and treatment in the adjuvant setting, there is no substitute for well-executed, large randomised clinical trials to define efficacy and determine the populations that are most likely to benefit from an intervention. Thus, enthusiasm remains for understanding the role of metformin in cancer through ongoing clinical research.
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Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Neoplasias/prevención & control , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Reposicionamiento de Medicamentos/métodos , HumanosAsunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , ADN Viral , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Sensibilidad y Especificidad , Manejo de Especímenes , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.
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Adenocarcinoma/química , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Neoplasias del Cuello Uterino/química , Adenocarcinoma/patología , Adenocarcinoma in Situ/química , Adenocarcinoma in Situ/patología , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/patología , Cuello del Útero/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Femenino , Humanos , Antígeno Ki-67/análisis , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/clasificación , Neoplasias del Cuello Uterino/patologíaRESUMEN
Primary liver cancer occurs less commonly among women than men in almost all countries. This discrepancy has suggested that hormone levels and/or exogenous hormone use could have an effect on risk, although prior studies have reached inconsistent conclusions. Thus, the current study was conducted to examine the relationship between menopausal hormone therapy (MHT) use and development of liver cancer. A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Controls were matched, at a 4-to-1 ratio, to women diagnosed with primary liver cancer between 1988 and 2011. A second match, based on whether the cases and controls had diabetes, was also conducted. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with liver cancer were estimated using conditional logistic regression adjusted for known risk factors. In the overall match, 339 women with liver cancer were matched to 1318 controls. MHT use was associated with a significantly lower risk of liver cancer (ORadj = 0.58, 95%CI = 0.37-0.90) especially among users of estrogen-only MHT (ORadj = 0.44, 95%CI = 0.22-0.88) and among past users (ORadj = 0.53, 95%CI = 0.32-0.88). Among the matched cases (n = 58) and controls (n = 232) with diabetes, the odds ratios were similar to the overall analysis (ORadj = 0.57, 95%CI = 0.09-3.53), but did not attain statistical significance. In the current study, MHT use, especially estrogen-only MHT use, was associated with a significantly lower risk of liver cancer. These results support the need of further investigation into whether hormonal etiologies can explain the variation in liver cancer incidence between men and women.
Asunto(s)
Terapia de Reemplazo de Estrógeno , Neoplasias Hepáticas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Oportunidad Relativa , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Use of antibiotics could alter human microbiota composition and decrease bacterial diversity. Such microbial dysbiosis may have implications in hepatocarcinogenesis; however, the association between antibiotic use and liver cancer risk has been minimally examined in humans. METHODS: We performed a nested case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink. Antibiotic use was obtained from prescription records. Multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression. RESULTS: Ever-use of prescription antibiotics was associated with a slightly increased risk of liver cancer, compared to non-use (OR=1.22, 95% CI=1.03-1.45). However, there was no clear dose-response relationship by the number of prescriptions or cumulative dose of antibiotic use, suggesting a non-causal association. CONCLUSIONS: Our results do not support a role of antibiotic use in liver cancer development.
Asunto(s)
Antibacterianos/efectos adversos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Investigación Biomédica/métodos , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Microbiota/efectos de los fármacos , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Reino UnidoRESUMEN
UNLABELLED: Tanzania has the highest burden of cervical cancer in East Africa. This study aims to identify perceived barriers and facilitators that influence scale-up of regional and population-level cervical cancer screening and treatment programs in Tanzania. Convenience sampling was used to select participants for this qualitative study among 35 key informants. Twenty-eight stakeholders from public-sector health facilities, academia, government, and nongovernmental organizations completed in-depth interviews, and a seven-member municipal health management team participated in a focus group discussion. The investigation identified themes related to the infrastructure of health services for cervical cancer prevention, service delivery, political will, and sociocultural influences on screening and treatment. Decentralizing service delivery, improving access to screening and treatment, increasing the number of trained health workers, and garnering political will were perceived as key facilitators for enhancing and initiating screening and treatment services. In conclusion, participants perceived that system-level structural factors should be addressed to expand regional and population-level service delivery of screening and treatment. IMPLICATIONS FOR PRACTICE: Tanzanian women have a high burden of cervical cancer. Understanding the perceived structural factors that may influence screening coverage for cervical cancer and availability of treatment may be beneficial for program scale-up. This study showed that multiple factors contribute to the challenge of cervical cancer screening and treatment in Tanzania. In addition, it highlighted systematic developments aimed at expanding services. This study is important because the themes that emerged from the results may help inform programs that plan to improve screening and treatment in Tanzania and potentially in other areas with high burdens of cervical cancer.
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Detección Precoz del Cáncer , Conocimientos, Actitudes y Práctica en Salud , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/economía , Femenino , Humanos , Aceptación de la Atención de Salud , Tanzanía , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/terapiaRESUMEN
BACKGROUND: HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. METHODS: We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia's most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. RESULTS: Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. CONCLUSIONS: The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed.
Asunto(s)
Infecciones por VIH/complicaciones , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/virología , Humanos , Incidencia , Tamizaje Masivo , Persona de Mediana Edad , Modelos Teóricos , Prevalencia , Neoplasias del Cuello Uterino/virología , Adulto Joven , Zambia/epidemiología , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVE: We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. METHODS: We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period after cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. RESULTS: A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR], 28-36 years). The median CD4+ cell count was 350 cells/µL (IQR, 214-470 cells/µL), and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI], 83%-95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 25% (17/67) cleared their initial hrHPV infection within 12 weeks of treatment, although 65% (11/17) had new hrHPV types detected. CONCLUSIONS: Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women, and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia.
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Crioterapia/métodos , Infecciones por VIH/complicaciones , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/terapia , Enfermedades del Cuello del Útero/terapia , Adolescente , Adulto , Estudios de Cohortes , Femenino , Papillomavirus Humano 16 , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven , ZambiaRESUMEN
BACKGROUND: Natural human papillomavirus (HPV) antibody titers have shown protection against subsequent HPV infection, but previous studies were restricted to few HPV genotypes. We examined the association of naturally occurring antibodies against 8 carcinogenic HPV types with subsequent infections. METHODS: A total of 2302 women enrolled in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study provided blood samples at baseline. Serum samples were tested for antibodies against 8 carcinogenic HPV genotypes (16, 18, 31, 33, 35, 45, 52, and 58) using a multiplex serology assay. We analyzed the relationship between HPV antibodies and HPV infection during 2 years of follow-up among women negative for the specific HPV type at baseline. RESULTS: Baseline seroprevalence for HPV16 L1 was associated with decreased risk of DNA positivity for HPV16 (odds ratio, 0.39 [95% confidence interval, .18-.86]) at ≥2 follow-up visits. We observed similar but nonsignificant decreased risks for HPV18 and 31. These findings were restricted to women reporting a new sex partner during follow-up. There was no association between baseline seroprevalence and detection of precancer during follow-up. CONCLUSIONS: Seroprevalence conferred protection against subsequent HPV infection for HPV16 and indicated possible protection for 2 other genotypes, suggesting that this effect is common to several HPV genotypes.
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Virus Oncogénicos , Papillomaviridae/genética , Papillomaviridae/inmunología , Infecciones por Papillomavirus/epidemiología , Inmunidad Adaptativa , Femenino , Genotipo , Humanos , Oportunidad Relativa , Papillomaviridae/clasificación , Infecciones por Papillomavirus/sangre , Estudios Seroepidemiológicos , Displasia del Cuello del Útero/virologíaRESUMEN
While urine-based sampling for human papillomavirus (HPV) is being explored as a simple and noninvasive approach for cervical cancer screening, data comparing HPV genotyping in urine and those in cellular sampling of the cervix and vulva, and their correlation with rigorously confirmed cervical disease status, are sparse. We performed HPV genotyping on voided-urine and clinician-collected vulvar and cervical samples from 72 women undergoing colposcopy. Although urine-based HPV carcinogenic HPV detection was lower (58.3%) than cervical (73.6%) and vulvar (72.1%) detection (P = 0.05 and 0.07, respectively), the agreement of urine HPV with cervical and vulvar HPV was moderate (kappa = 0.55) and substantial (kappa = 0.62), respectively. Urine-based carcinogenic HPV detection had a clinical sensitivity of 80.8% (95% confidence interval [CI] = 60.7 to 93.5) and a specificity of 53.3% (95% CI = 37.9 to 68.3) for diagnosing cervical intraepithelial neoplasia grades 2/3 (CIN2/3) on histology; 90.0% of CIN3 was positive for urine HPV. The corresponding sensitivity and specificity values for vulvar sampling were 92% (95% CI = 74 to 99) and 40.5% (95% CI = 25.6 to 56.7), and those for cervical sampling were 96.2% (95% CI = 80.4 to 99.9) and 40% (95% CI = 25.7 to 55.7), respectively. HPV16 was the most common carcinogenic genotype detectable in 25% of urine, 33.8% of vulvar, and 31.9% of cervical samples overall, with prevalence increasing with cervical disease grade, regardless of the sampling method. Stronger cervical HPV PCR signal strengths were associated with increased frequency of urine HPV detection. In summary, the relatively lower detection rates but comparable clinical performance of urine-based HPV sampling underscore the need for larger studies to evaluate urine-based sampling for cervical cancer screening, epidemiologic studies, and postvaccination HPV disease surveillance.
Asunto(s)
Cuello del Útero/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Orina/virología , Vulva/virología , Adulto , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.
Asunto(s)
Enfermedades del Ano/diagnóstico , Técnicas de Genotipaje/métodos , Homosexualidad Masculina , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Adolescente , Adulto , Enfermedades del Ano/virología , Técnicas Citológicas/métodos , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Yunnan has one of the oldest and the most severe human immunodeficiency virus (HIV) epidemics in China. We conducted an observational study to evaluate the human papillomavirus (HPV) genotype distribution in relation to cervical neoplastic disease risk among HIV-infected women in Yunnan. METHODS: We screened 301 HIV-infected non-pregnant women in Mangshi prefecture in Yunnan province. All consenting participants underwent simultaneous and independent assessment by cervical cytology, colposcopy-histopathology, and HPV genotyping. Unadjusted and multivariable-adjusted multinomial logistic regression analysis was conducted to evaluate factors associated with single or multiple carcinogenic HPV genotypes. RESULTS: HPV genotypes were present in 43.5% (131/301) overall, and carcinogenic HPV genotypes were present in 37.5% (113/301) women. Among women with carcinogenic HPV genotypes, 80 (70.8% of 113) had a single carcinogenic HPV type, while 33 (29.2%) women had multiple (2 or more) carcinogenic HPV types. Overall, the most common carcinogenic HPV types were HPV52 (7.3%), HPV58 (6.6%), HPV18 (6.3%), HPV16 (6.0%), and HPV33 (5.3%). In women with cervical precancerous lesions (i.e., high-grade squamous intraepithelial lesions [HSIL] on cytology or cervical intraepithelial neoplasia grade 2 or worse [CIN2+] detected on colposcopy-histology), the most commonly detected genotypes were HPV16 (28.6%), HPV52 (25.0%), HPV58 (17.9%), HPV18 (10.7%) and HPV31 (10.7%). Increasing age was an independent risk factor associated with presence of single carcinogenic HPV types (adjusted odds ratio: 1.04, 95%CI: 1.01-1.07, p = 0.012) but not with the presence of multiple carcinogenic types in the multivariable-adjusted models. CONCLUSIONS: As HIV-infected women continue to live longer on antiretroviral therapy in China, it will be increasingly important to screen for, and prevent, HPV-associated cervical cancer in this population, especially given the wide diversity and multiplicity of HPV genotypes.