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Cervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome.
Despite advances in treatment, the disease's advanced stages and spread to other parts of the body often lead to poor outcomes. This highlights the urgent need for better diagnostic and treatment methods tailored to each patient and their specific tumour. Treatment for cervical cancer usually involves a combination of therapies. Chemotherapy and focused radiation therapy are commonly used before or after surgery to improve outcomes. However, some patients develop resistance to these treatments, either from the start or after initially responding to therapy. This resistance can make treatment less effective and increase the risk of side effects. Chemotherapy resistance is often linked to changes in the genes and proteins of cancer cells. These changes disrupt the normal balance within the cells, making them more prone to grow and survive, resist cell death, and repair DNA damage caused by treatment. Despite progress in cancer research and treatment, drug resistance remains a significant challenge. This review aims to explore how acquired genetic mutations contribute to drug resistance in cervical cancer. By understanding these mutations better, researchers and clinicians in low- to middle-income countries can develop more effective treatment strategies to improve outcomes for patients.
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Resistencia a Antineoplásicos , Mutación , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Femenino , Resistencia a Antineoplásicos/genética , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacologíaRESUMEN
Background: Two-thirds of people living with human immunodeficiency virus type 1 (HIV-1) infection reside in Sub-Saharan Africa, where there are the highest prevalence and incidence rates of human papillomavirus (HPV) infection. Both infections are sexually transmitted and enter the body via the epithelium. This review describes the extent of involvement of the epithelium in each infection in the female genital tract. Methods: A narrative review was conducted on the role of the epithelium in HPV and HIV-1 infections. Results: An intact epithelial barrier is the predominant form of protection against viral entry and infection, including from HIV-1 and HPV. HPV is an intraepithelial pathogen, and thus, its growth and amplification, which are dependent on squamous cell differentiation, occur in the epithelium. It gains entry to the basal cells of the stratified squamous epithelium via micro-abrasions or other epithelial injuries that expose the basement membrane. HIV-1, conversely, passes through the epithelium to infect subepithelial tissues. Following deposition of the HIV-1-containing inoculum into the lumen, the virus enters the mucosa through breaks in the epithelial barrier within hours of infection. Further, HIV-1 penetrates the epithelium via various mechanisms, including paracellular passage or across epithelial cells through transcytosis. The capture of the virus from the mucosal surface by intraepithelial and/or subepithelial target cells has also been documented. Conclusions: Epithelial disruption is the major pathogenetic pathway in HIV-1 and HPV infections. Therefore, biochemical compounds that strengthen the epithelial barrier must be prioritized to prevent these infections.
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BACKGROUND: Cervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk. METHODS: Primary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies. RESULTS: The only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%]. DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%]. CONCLUSION: Using hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite.
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BACKGROUND: Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use. METHODS: The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires. RESULTS: One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer. CONCLUSION: The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.
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Conocimientos, Actitudes y Práctica en Salud , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Conducta Sexual , Neoplasias del Cuello Uterino , Humanos , Femenino , Sudáfrica/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Adolescente , Infecciones por Papillomavirus/prevención & control , Adulto Joven , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Encuestas y Cuestionarios , Vacunación/psicología , Vacunación/estadística & datos numéricosRESUMEN
OBJECTIVE: Guidelines for effective triage following positive primary high-risk human papillomavirus (HPV) screening in low- and middle-income countries with high human immunodeficiency virus (HIV)-prevalence have not previously been established. In the present study, we evaluated the performance of three triage methods for positive HPV results in women living with HIV (WLHIV) and without HIV in Botswana. METHODS: We conducted baseline enrollment of a prospective cohort study from February 2021 to August 2022 in South-East District, Botswana. Non-pregnant women aged 25 or older with an intact cervix and no prior diagnosis of cervical cancer were systematically consented for enrollment, with enrichment of the cohort for WLHIV. Those who consented completed a questionnaire and then collected vaginal self-samples for HPV testing. Primary HPV testing for 15 individual genotypes was conducted using Atila AmpFire® HPV assay. Those with positive HPV results returned for a triage visit where all underwent visual inspection with acetic acid (VIA), colposcopy, and biopsy. Triage strategies with VIA, colposcopy and 8-type HPV genotype restriction (16/18/31/33/35/45/52/58), separately and in combination, were compared using histopathology as the gold standard in diagnosing cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+). RESULTS: Among 2969 women enrolled, 1480 (50%) tested HPV positive. The cohort included 1478 (50%) WLHIV; 99% were virologically suppressed after a mean of 8 years on antiretroviral therapy. In total, 1269 (86%) women had histopathology data for analysis. Among WLHIV who tested positive for HPV, 131 (19%) of 688 had CIN2+ compared with 71 (12%) of 581 in women without HIV. Screening by 8-type HPV genotype restriction was more sensitive as triage to detect CIN2+ in WLHIV 87.79% (95% CI: 80.92-92.85) and women without HIV 85.92% (95% CI: 75.62-93.03) when compared with VIA (WLHIV 62.31% [95% CI: 53.39-70.65], women without HIV 44.29% [95% CI: 32.41-56.66]) and colposcopy (WLHIV 70.77% [95% CI: 62.15-78.41], women without HIV 45.71% [95% CI: 33.74-58.06]). However, 8-type HPV genotype restriction had low specificity in WLHIV of 30.88% (95% CI: 27.06-34.90) and women without HIV 37.06% (95% CI: 32.85-41.41). These results were similar when CIN3+ was used as the outcome. When combining 8-type HPV genotype restriction with VIA as the triage strategy, there was improved specificity to detect CIN2+ in WLHIV of 81.65% (95% CI: 78.18-84.79) but dramatically reduced sensitivity of 56.15% (95% CI: 47.18-64.84). CONCLUSIONS: Eight-type HPV genotype restriction is a promising component of effective triage for HPV positivity. However, novel triage strategies in LMICs with high HIV prevalence may be needed to avoid the trade-off between sensitivity and specificity with currently available options. CLINICAL TRIALS REGISTRATION: This study is registered on Clinicaltrials.gov no. NCT04242823, https://clinicaltrials.gov/ct2/show/NCT04242823.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Embarazo , Masculino , Estudios Prospectivos , VIH , Triaje/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Botswana/epidemiología , Prevalencia , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Colposcopía , Genotipo , Ácido Acético , Detección Precoz del Cáncer/métodosRESUMEN
BACKGROUND: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. METHODS: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. RESULTS: The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. CONCLUSION: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.
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Background: Sexual history-taking competence in medical students is an essential skill that they need to acquire. It requires them to learn to develop comfort in using sexuality-related language and raising the subject with patients. Sexual history exploration skills are inadequately taught in a significant number of medical schools. Aim: We studied comfort levels in using sexuality-related language in medical students who had no training yet in history taking. Methods: First-year medical students in a South African university engaged in an exercise in pairs-a dyad-alternating the role of interviewer and interviewee. Provided questions and answers were offered to the students, who videotaped their dyad interview and uploaded it to a safe university environment for peer review. Outcomes: As part of the exercise, students rated their comfort in the interview for 35 questions on a 5-point Likert scale. Students then participated in online discussion forums with fellow students and tutors on their experience. Results: Students posing the questions, the interviewers, were significantly more comfortable with the questions than interviewees. Total comfort scores over the 35 questions showed a roughly normal distribution for both. Questions with explicit sexual behavior or vocabulary were rated more uncomfortable by interviewers as well as interviewees. The total scores for interviewers showed a distribution with a longer tail toward discomfort. Female interviewees were significantly more uncomfortable than male interviewees, but this was not the case for interviewers. Dyads of 2 females were significantly more uncomfortable than mixed-gender and 2-male dyads. Qualitative data showed wide acceptance of the exercise by students, with increasing confidence and comfort in using sexually explicit terms in strong appreciation of the responder's perspective in the exercise, as well as awareness that receiving a question-the patient's position-is more uncomfortable. Clinical Translation: Data indicate that comfort assessment in asking sexuality-related questions with expected different levels of comfort and discomfort is a valuable measure that can evaluate progress in this skill. The data also suggest the need for students to select profiles and questions to provide a trauma-informed approach, knowing that some of the medical students will have experienced sexually related trauma, as in the general population. Strengths and Limitations: This study provides a method and student feedback in teaching sexual history elicitation and increasing comfort with sexual language in a clinical context. The study is limited to first-year medical students. Conclusion: Histories with provided questions and answers allow for rating of comfort and provision of trauma-informed education in developing sexual history exploration clinical skills.
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BACKGROUND: Stellenbosch University's (SU) Faculty of Medicine and Health Sciences (FMHS), developed a sexual health course to be integrated throughout the revised medical curriculum. AIM: To use the Sexual Health Education for Professionals Scale (SHEPS) to gather baseline and future follow-up data to inform curriculum development and evaluation. SETTING: The first-year medical students (N = 289) of the FMHS SU. METHODS: The SHEPS was answered before the start of the sexual health course. The knowledge, communication and attitude sections were answered with a Likert-type scale. Students had to describe their perceived confidence in their knowledge and communication skills to care for patients within specific sexuality-related clinical scenarios. The attitude section measured the students' level of agreement or disagreement on sexuality-related opinion statements. RESULTS: The response rate was 97%. Most students were female, and 55% of the class were first taught about sexuality in the age group 13-18 years. The students had more confidence in their communication skills than knowledge before any tertiary training. The attitude section revealed a binomial distribution, ranging from acceptance to a more restrictive attitude towards sexual behaviour. CONCLUSION: It is the first time the SHEPS has been used in a South African context. The results provide novel information about the range of perceived sexual health knowledge, skills and attitudes of first-year medical students before they start tertiary training.Contribution: Findings from this study will guide content development and evaluation of the sexual health course at the institution where the study was conducted, as well as allow for culture sensitive education.
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Salud Sexual , Estudiantes de Medicina , Humanos , Femenino , Adolescente , Masculino , Salud Sexual/educación , Universidades , Conducta Sexual , CurriculumRESUMEN
OBJECTIVE: Screening with primary human papillomavirus (HPV) testing has been evaluated in highly prescreened populations with lower HPV and HIV prevalence than what is the case in South Africa. High prevalence of HPV and underlying precancer in women living with HIV (WLWH) affect the clinical performance of screening tests significantly. This study investigates the utility and performance of an extended genotyping HPV test in detection of precancer in a population with a high coinfection rate with HIV. METHODS: A total of 1,001 women aged 25 to 65 years with no cervical cancer screening in the preceding 5 years were tested with cytology and primary extended genotyping HPV testing. The cohort of 1,001 women included 430 WLWH (43.0%) and 564 HIV-negative (56.3%) women. RESULTS: Abnormal cytology (atypical squamous cells of undetermined significance or higher) was significantly higher in WLWH (37.2% vs 15.9%) and high-grade squamous intraepithelial lesion or above (23.5% vs 5.2%). The WLWH also tested positive more often for any HPV type (44.3% vs 19.6%; p < .0001) The specificity for cervical intraepithelial neoplasia 2+ at 91.2% of a combination of HPV types, 16/18/45 (very high risk) and 31/33/58/52 (moderate risk), performed better than cytology or any HPV-positive result to predict cervical intraepithelial neoplasia 3+ on histology. The additional genotype information supports direct referral to treatment or colposcopy in a larger proportion of the screen-positive population. CONCLUSIONS: The potential contribution of extended genotyping is demonstrated. The ideal choice of sensitivity and specificity ultimately depends on the health budget. More information will allow a screening algorithm, guiding management according to risk.
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Coinfección , Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Coinfección/epidemiología , Infecciones por VIH/epidemiología , Colposcopía , Detección Precoz del CáncerRESUMEN
BACKGROUND: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. METHODS: In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. RESULTS: Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003]). CONCLUSIONS: Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , VIH , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Detección Precoz del Cáncer , Estudios de Cohortes , Sudáfrica/epidemiología , Displasia del Cuello del Útero/diagnóstico , Metilación de ADN , Papillomaviridae/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genéticaRESUMEN
OBJECTIVE: This study aimed to determine 5-year progression-free and overall survival in patients with uterine carcinosarcoma, to determine clinical and surgical-pathologic features, to recognize patterns of recurrence and to identify prognostic factors influencing progression-free survival (PFS) and overall survival (OS). DESIGN: This was a single institution, retrospective 10-year review of patients treated at Tygerberg Hospital in South Africa with pathologically confirmed uterine carcinosarcoma. METHODS: A total of 61 patients were studied. Demographic, clinicopathological, treatment and outcome information were obtained. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the effects of variables on PFS and OS. RESULTS: Eighteen patients (29%) presented as FIGO stage I disease, 5 patients (8%) as stage II, 16 patients (26%) as stage III and 22 patients (36%) as stage IV disease. Fifty of the 61 patients (82%) had surgery. Five-year PFS and 5-year OS were 17.3% (CI 8.9%-27.9%) and 19.7% (CI 10.6%-30.8%), respectively. Seventeen patients presented with recurrence of which 5 (29.4%) were local and 12 (70.6%) were outside the pelvis. In the univariate analysis, tumour diameter ≥ 100mm (HR 4.57; 95% CI 1.59-13.19; p-value 0.005) was associated with 5-year PFS and in univariate analysis of OS, a positive family history (HR 0.42; 95% CI 0.18-0.99; p-value 0.047), receiving a full staging operation (HR 0.37; 95% CI 0.18-0.78; p-value 0.008) and receiving any other modality of treatment, with or without surgery, (HR 0.48; 95% CI 0.27-0.85; p-value 0.012) were associated with better survival. An abnormal cervical smear (HR 2.4; 95% CI 1.03-5.6; p-value 0.041), late-stage disease (HR 3.48; 95% CI 1.79-6.77; p-value < 0.001), presence of residual tumour (HR 3.66; 95% CI 1.90-7.02; p-value < 0.001), myometrial invasion more than 50% (HR 2.29; 95% CI 1.15-4.57; p-value 0.019), cervical involvement (HR 3.38; 95% CI 1.64-6.97; p-value 0.001) and adnexal involvement (HR 3.21; 95% CI 1.56-6.63; p-value 0.002) were associated with a higher risk of death. In the multivariate analysis, full staging operation was associated with a risk of progression of disease (HR 3.49; 95% CI 1.17-10.41; p-value 0.025). Advanced stage (HR 4.2; 95% CI 2.09-8.44; p-value < 0.001) was associated with a higher risk of death. Any other modality of treatment (HR 0.28; 95% CI 0.15-0.53; p-value < 0.001) and full staging laparotomy (HR 0.27; 95% CI 0.12-0.59; p-value 0.001) was a protective factor for death. CONCLUSIONS: Carcinosarcoma is an aggressive cancer with poorer survival in this specific cohort than has been described in other contemporary cohorts. Biological or genetic factors are a possible explanation for lower overall survival in this population. Although it is also possible that later diagnosis and poor access to health care contribute to poorer survival. Most recurrences occur outside of the pelvis. Full staging surgery (including pelvic lymphadenectomy) and additional use of other modalities (either for radical or palliative intent) improve survival.
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Carcinosarcoma , Neoplasias Uterinas , Carcinosarcoma/patología , Carcinosarcoma/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Uterinas/cirugíaRESUMEN
OBJECTIVE: The platform provided by human papillomavirus (HPV) vaccination for linked public health interventions to improve cervical cancer prevention remains incompletely explored. The Vaccine And Cervical Cancer Screen (VACCS) cross-sectional observation trials aimed to evaluate the efficacy of school-based HPV vaccination linked with maternal cervical cancer screening. METHODS: Girls from 29 schools in two provinces in South Africa were invited in writing to receive HPV vaccination. Two approaches to informed consent were compared, namely an audiovisual presentation (VACCS1) and in written format (VACCS2). Markers of vaccine uptake and coverage were calculated, namely uptake among the invited and consented cohorts, and rates of completion and sufficient vaccination. Mothers and female guardians received educational material about cervical cancer, and either a self-sampling device or an invitation to attend existing screening facilities. Knowledge was assessed via structured questionnaires (before and after), and screening uptake was self-reported and directly assessed and compared between these approaches. RESULTS: Vaccine acceptance among 5137 invited girls was similar for the two methods of consent; 99.3% of consented girls received a first dose; overall completion rate was 90.5%. More girls were vaccinated using a two-dose (974/1016 (95.9%)) than a three-dose regimen (1859/2030 (91.6%)). The questionnaire (n=906) showed poor maternal knowledge which improved significantly (p<0.05) after health education; only 54% of mothers reported any previous screening. The offer of a self-sampling device (n=2247) was accepted by 43.9% of mothers, but only 26% of those invited to screen at existing facilities (n=396) reported subsequent screening. CONCLUSIONS: Successful linking of primary health interventions to control cervical cancer was demonstrated. School-based HPV vaccination, linked to health education, self-sampling, and molecular screening resulted in significant improvements in knowledge and screening.
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Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Madres , Papillomaviridae , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Aceptación de la Atención de Salud , Sudáfrica/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , VacunaciónRESUMEN
OBJECTIVE: Young women in South Africa are highly affected by sexually transmitted infections (STI), like C. trachomatis (CT) and N. gonorrhoeae (NG). We aimed to estimate the incidence of CT and NG, and its determinants, among young women from the Western Cape, South Africa, participating in an HPV vaccine trial (the EVRI study). METHODS: HIV-negative women aged 16-24 years were enrolled between October 2012 and July 2013. At enrolment and month 6 participants were screened for CT and NG (Anyplex CT/NG real-time detection method). A questionnaire on demographic and sexual history characteristics was completed at enrolment and month 7. Treatment for CT and/or NG was offered to infected participants. Incidence rates (IR) of CT and NG were estimated. Determinants of incident CT and NG infections were assessed using Poisson regression. RESULTS: 365 women were tested for CT and/or NG at least twice. Prevalence of CT and NG at baseline was 33.7% and 10.4%, respectively. Prevalence of co-infection with CT and NG was 7.1%. During 113.3 person-years (py), 48 incident CT infections were diagnosed (IR = 42.4 per 100 py, 95% confidence interval (CI) 31.9-56.2). Twenty-nine incident NG were diagnosed during 139.3 py (IR = 20.8 per 100 py, 95%CI 14.5-29.9). Prevalent CT infection at baseline was associated with incident CT (adjusted incidence rate ratio (aIRR) 5.8, 95%CI 3.0-11.23. More than three lifetime sex partners increased the risk for incident NG (3-4 partners aIRR = 7.3, 95%CI 2.1-26.0; ≥5 partners aIRR = 4.3, 95%CI 1.1-17.5). CONCLUSIONS: The IR of bacterial STIs among young women in the Western Cape is very high. Besides being previously infected and a higher lifetime number of sex partners, no other risk factors were found for CT and NG, suggesting that the majority of these women were at risk. This indicates the need for intensified prevention of STIs as well as screening and treatment programs to increase sexual health in this region.
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Infecciones por Chlamydia/epidemiología , Gonorrea/epidemiología , Adolescente , Adulto , Infecciones por Chlamydia/microbiología , Infecciones por Chlamydia/virología , Chlamydia trachomatis/patogenicidad , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , Femenino , Gonorrea/microbiología , Gonorrea/virología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Incidencia , Tamizaje Masivo/métodos , Neisseria gonorrhoeae/patogenicidad , Prevalencia , Factores de Riesgo , Conducta Sexual/fisiología , Parejas Sexuales , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/microbiología , Sudáfrica/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Cancer screening programs hold much potential for reducing the cervical cancer disease burden in developing countries. The aim of this study was to determine the feasibility of mobile health (mHealth) phone technology to improve management and follow-up of clients with cervical cancer precursor lesions. METHODS: A sequential mixed methods design was employed for this study. Quantitative data was collected using a cross-sectional survey of 364 women eligible for a Pap smear at public sector health services in Cape Town, South Africa. Information was collected on socio-demographic status; cell phone ownership and patterns of use; knowledge of cervical cancer prevention; and interest in Pap smear results and appointment reminders via SMS-text messages. Descriptive statistics, crude bivariate comparisons and logistic regression models were employed to analyze survey results. Qualitative data was collected through 10 in-depth interviews with primary health care providers and managers involved in cervical cancer screening. Four focus group discussions with 27 women attending a tertiary level colposcopy clinic were also conducted. Themes related to loss of mobile phones, privacy and confidentiality, interest in receiving SMS-text messages, text language and clinic-based management of a SMS system are discussed. Thematic analyses of qualitative data complemented quantitative findings. RESULTS: Phone ownership amongst surveyed women was 98% with phones mostly used for calls and short message service (SMS) functions. Over half (58%) of women reported loss/theft of mobile phones. Overall, there was interest in SMS interventions for receiving Pap smear results and appointment reminders. Reasons for interest, articulated by both providers and clients, included convenience, cost and time-saving benefits and benefits of not taking time off work. However, concerns were expressed around confidentiality of SMS messages, loss/theft of mobile phones, receiving negative results via SMS and accessibility/clarity of language used to convey messages. Responsibility for the management of a clinic-based SMS system was also raised. CONCLUSIONS: Results indicated interest and potential for mHealth interventions in improving follow-up and management of clients with abnormal Pap smears. Health system and privacy issues will need to be addressed for mHealth to achieve this potential. Next steps include piloting of specific SMS messages to test feasibility and acceptability in this setting.
Asunto(s)
Prueba de Papanicolaou/métodos , Lesiones Precancerosas/prevención & control , Sistemas Recordatorios , Telemedicina/estadística & datos numéricos , Envío de Mensajes de Texto/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Adulto , Teléfono Celular/estadística & datos numéricos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto JovenRESUMEN
The incidence of cancer in pregnancy is increasing. The most frequent malignancies include breast and cervical cancers. Diagnosis may be complicated by late presentation. Imaging during pregnancy should consider risks to the fetus. Diagnostic work-up, including tumor markers, can be influenced by the physiology of pregnancy. Treatment of cancer can often be safely administered with good maternal and fetal outcomes. Chemotherapy, radiotherapy, and surgery must be adapted to the pregnancy state. Counselling and emotional support are an essential part of management.
Asunto(s)
Neoplasias de la Mama/terapia , Complicaciones Neoplásicas del Embarazo/terapia , Neoplasias del Cuello Uterino/terapia , Neoplasias de la Mama/patología , Femenino , Feto/patología , Humanos , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: In South Africa, where HIV prevalence among adults is 18.9%, cervical carcinoma is the second most common malignancy in women. However, oncology services are considerably more accessible in South Africa than in many neighbouring countries. This study reports five-year overall survival in a cohort of HIV-positive and -negative cervix carcinoma patients undergoing primary radiotherapy at a single institution in South Africa. METHODS: Prospective cohort study of all locally advanced cervix carcinoma patients referred for radiotherapy (EBRT) from July 2007 to November 2011. Overall survival (OS) was the primary end-point. RESULTS: A total of 492 patients commenced treatment with radical intent, including 71 HIV-positive patients (14.4%) and 421 HIV-negative patients (85.6%). Of the 433 who were prescribed standard fractionation EBRT, 384 were prescribed concurrent platinum-based chemotherapy (88.7%). Fewer HIV-positive than HIV-negative patients (58.5% vs. 76.1%; pâ¯=â¯0.007) completed ≥4â¯cycles. The OS of HIV-negative patients was 49.5% (95%CI; 44.6%-54.4%) at 5â¯years. The OS of HIV-positive patients was significantly lower, 35.9% (95% CI; 23.9%-48.0%) at 5â¯years (pâ¯=â¯0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, presence of hydronephrosis, and delivery of concurrent chemotherapy. CONCLUSION: In our large cohort, HIV-positive patients had poorer survival than HIV-negative patients, however nearly 40% survived 5â¯years, justifying provision of the best standard of care to HIV-positive patients with cervical carcinoma.
Asunto(s)
Quimioradioterapia , Infecciones por VIH/complicaciones , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/inmunología , Humanos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/mortalidadRESUMEN
OBJECTIVE: To estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial. METHODS: HIV-negative women aged 16-24â years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2 and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence. RESULTS: Among 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08). CONCLUSIONS: Among high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease. TRIAL REGISTRATION NUMBER: NCT01489527; Post-results.
Asunto(s)
Coinfección/epidemiología , Seronegatividad para VIH , Infecciones por Papillomavirus/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Consumo de Bebidas Alcohólicas/epidemiología , Chlamydia trachomatis/aislamiento & purificación , Coinfección/microbiología , Coinfección/virología , Femenino , Genotipo , Gonorrea/epidemiología , Gonorrea/microbiología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Herpes Genital/epidemiología , Herpes Genital/virología , Herpesvirus Humano 2 , Humanos , Área sin Atención Médica , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/administración & dosificación , Prevalencia , Conducta Sexual , Parejas Sexuales , Enfermedades de Transmisión Sexual/microbiología , Enfermedades de Transmisión Sexual/virología , Sudáfrica/epidemiología , Sífilis/epidemiología , Sífilis/microbiología , Adulto JovenRESUMEN
BACKGROUND: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. METHODS: Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. RESULTS: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. CONCLUSION: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.
RESUMEN
OBJECTIVE: The aim of this study was to explore and understand women's experience with cervical cancer screening and with the referral pathways for abnormal Papanicolau (Pap) smears. DESIGN AND SETTING: Focus group discussions were conducted with first time colposcopy clinic attendees at a tertiary hospital colposcopy clinic in Cape Town, South Africa during November 2014. A thematic analysis was conducted to identify key themes. Initial coding categories were drawn from the interview guide. PARTICIPANTS: 27 women participated in 4 focus group discussions. RESULTS: Participants mean age was 34â years, most did not complete secondary level education and were unemployed. Negative community opinions relating to Pap smears and colposcopy referral might deter women from seeking treatment. Having a gynaecological symptom was the most commonly cited reason for having a Pap smear. Fear of having a HIV test performed at the same time as Pap smear and low encouragement from peers, were factors identified as potential access barriers. Participants commented on insufficient or lack of information from primary providers on referral to the colposcopy clinic and concerns and apprehension during waiting periods between receiving results and the colposcopy appointment were discussed. CONCLUSIONS: There is a strong and urgent need to improve current knowledge about cervical cancer and Pap smears and the necessity and benefits of timely access to screening programmes, results and treatment. Strategies such as community health education programmes and mass media interventions could be employed to disseminate cervical cancer information and address negative community perceptions. Better training and support mechanisms to equip healthcare providers with the skills to convey cervical cancer information to women are needed. The use of short message service (SMS) to deliver Pap smear results and provide patients with more information should be considered to improve waiting times for results and alleviate apprehension during waiting periods.
Asunto(s)
Colposcopía/psicología , Países en Desarrollo , Detección Precoz del Cáncer/psicología , Aceptación de la Atención de Salud/psicología , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Comunicación , Vías Clínicas , Femenino , Grupos Focales , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud , Humanos , Persona de Mediana Edad , Prueba de Papanicolaou/psicología , Educación del Paciente como Asunto , Investigación Cualitativa , Derivación y Consulta , Sudáfrica , Factores de Tiempo , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/psicología , Listas de Espera , Adulto JovenRESUMEN
OBJECTIVE: The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). METHODS: HIV-negative, sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. RESULTS: HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. CONCLUSIONS: Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.