Sexual Reproductive Health and Rights Repository (Aga Khan University)
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Role of phosphatidylinositol 3-kinase and its catalytic unit PIK3CA in cervical cancer: a mini-review
Get PDFIn complicated disorders like cancer, signaling pathways form a tangled network. Targeting one gene may result in an unfavorable reaction from another off-target gene. Such entwined complexities may result in treatment resistance or failure in cancer patients. The PI3K/Akt/mTOR (phosphoinositol 3-kinase/protein kinase B/mammalian target of rapamycin) pathway is dysregulated in cervical cancer and is used as a biomarker for therapy. PI3K is a kinase that consists of a regulatory and catalytic domain and has phosphorylation capability. Class I components like the catalytic part (PIK3CA and PIK3CD) and regulatory part (like PIK3R1, PIK3R2, PIK3R3, and PIK3R5) are associated with oncogenesis and growth factors in cervical cancer. This review is aimed at discussing the involvement of the PI3K component of the PI3K/Akt/mTOR network in cervical cancer. Specifically, class I catalytic subunit PIK3CA has been identified as a pharmacological target, making it therapeutically significant. Apart from discussing the function of PI3K and PIK3CA in cervical cancer, we also discuss their inhibitors, which may be beneficial in treating cervical cancer
Definitive vs palliative pelvic radiation for patients with newly diagnosed stage IVB cervical cancer treated with bevacizumab – An exploratory study
Get PDFObjective:
Platinum-based chemotherapy and bevacizumab is the standard treatment for stage IVB cervical cancer. When metastases resolve, the benefit of radiating the primary tumor is unclear. We investigate the effect of pelvic radiation on PFS following chemotherapy and bevacizumab in stage IVB cervical cancer.
Methods:
This is a retrospective series of 29 patients with stage IVB cervical cancer treated with platinum-based chemotherapy and bevacizumab. 3 subgroups were evaluated: definitive pelvic radiation, palliative radiation, and no radiation. The primary outcome was the mean PFS. Progression was determined radiographically. Kaplan-Meier method and the log-rank test for equality analyzed OS and PFS.
Results:
The median OS was 38.4 months. 11 patients (38%) received definitive radiation, 9 (31%) received palliative and 9 (31%) received no radiation. 7/8 in the palliative group, 7/10 who received no radiation and all in the definitive group experienced progression. The median PFS was 7.5 months and not statistically different (p = 0.62). The median OS was not attained in the definitive group, was 23 months [19.6, -] for the palliative group and 19 months [24.9–45.4] for the no radiation group (p = 0.13). OS was higher in patients receiving definitive radiation vs all others (median OS survival not reached vs 6.6 months, p = 0.04). No difference in PFS between those receiving definitive radiation vs others (12 months vs 5.1 months p = 0.32).
Conclusion:
Definitive radiation is associated with improved survival among in stage IVB cervical cancer treated with chemotherapy and bevacizumab. This association could be due to treatment, patient, or disease factors associated with improved oncologic outcomes. In absence of higher-level data, shared decision-making with consideration for comorbidities and performance status should be employed
Prevalence and predictors of cervical cancer screening among reproductive age group women: evidence from cross-sectional study in Rohtak and Delhi
Get PDFBackground:
The present study aims to estimate the prevalence and determine the factors for cervical cancer screening among women in the reproductive age group in Delhi and Rohtak, India.
Methods:
The data were utilized from a survey conducted as part of a larger study to increase the access to cervical cancer screening and care by MAMTA-Health Institute for Mother and Child in collaboration with the Health Departments of Palam, New Delhi, and Rohtak, Haryana between 2015 and 2017. Data pertaining to the socio-economic and demographic information along with the information related to cervical cancer screening were utilized for the present study. The sample size was 1020 women in reproductive age group. Descriptive statistics (percentage and frequency distribution), bivariate analysis along with multivariable analysis were done to represent the results. The Fisher exact test was used to test the level of significance during bivariate analysis.
Results:
About 35.2% [Delhi: 44.9% and Rohtak: 23.8%] of the respondents had heard about cervical cancer screening. Further about 3.9% [Delhi-2.9% and Haryana-5.1%] had screened for cervical cancer. Women who had heard about cervical cancer were five times more likely to go for screening [aOR: 5.27; CI: 2.53,10.96]. It was found that women over 30 years of age had 12.04 significantly higher odds of going for cervical cancer screening in reference to women aged 30 years and less [aOR: 12.04; CI: 3.01,53.20]. Women from households with a monthly income of more than 15000 had 2.98 significantly higher odds of going for cervical cancer screening in reference to women from households with an income of 5000 and less [aOR : 2.98; CI: 1.12,9.09].
Conclusion:
Findings suggest that awareness about cervical cancer screening test along with its thorough knowledge about its benefits would be an effective intervention to increase the uptake of cervical cancer screening
HPV types 16/18 L1 E6 and E7 proteins seropositivity and cervical cancer risk in HIV-positive and HIV-negative black South African women
Get PDFBackground:
In populations with high rates of human immunodeficiency virus (HIV)-coinfection, the nature of the relationship between human papillomavirus (HPV)-16 and -18 (L1, E6 and E7) antibodies and cervical cancer is still uncertain. We measured the association between seropositivity to HPV (L1, E6 and E7) proteins and cervical cancer among black South African women with and without HIV co-infection.
Methods:
We used questionnaire data and serum collected from consecutively recruited patients with a newly diagnosed cancer from the Johannesburg Cancer Study from 1346 cervical cancer cases and 2532 controls (diagnosed with other non-infection related cancers). Seropositivity to HPV proteins was measured using a multiplex serological assay based on recombinant glutathione S-transferase (GST) fusion proteins. We measured associations between their presence and cervical cancer using unconditional logistic regression models and evaluated the sensitivity and specificity of these HPV biomarkers.
Results:
Among controls, HIV-negative women from rural areas compared to urban had significantly higher HPV seroprevalence, HPV16 E7 (8.6% vs 3.7%) and HPV18 E7 (7.9% vs 2.0%). HPV16 E6 and E7 antibodies were positively associated with cervical cancer in HIV-positive (Adjusted Odds Ratio (AOR) = 33; 95% CI 10–107) and HIV-negative women (AOR = 97; 95% CI 46–203). In HIV-positive women, HPV E6/E7 antibodies had low sensitivity (43.0%) and high specificity (90.6%) for cervical cancer detection. In HIV-negative women, HPV E6/E7 antibodies sensitivity was 70.6% and specificity was 89.7%.
Conclusions:
Our data show that HPV (L1, especially E6 and E7) antibody positivity is associated with cervical cancer in both HIV-positive and HIV-negative women. Nonetheless, being HIV-positive plays an important role in the development of cervical cancer
A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome
Get PDFThere is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with Chlamydia trachomatis (CT) significantly impacts the foreskin proteome composition. We developed and optimized a shotgun liquid chromatography coupled tandem mass spectrometry (MS)-based proteomics approach and utilized this on foreskins collected at medical male circumcision (MMC) from 16 aSTI+ men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed (DE) proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI, whereas homotypic cell–cell adhesion proteins were enriched in foreskin tissue from men without an aSTI. Collectively, our data show that asymptomatic urethral sexually transmitted infections result in profound alterations in epithelial tissue that are associated with depletion of barrier integrity and immune activation
A cohort analysis of sexually transmitted infections among different groups of men who have sex with men in the early era of HIV pre-exposure prophylaxis in France
Get PDFBackground:
MSM are at particular risk of STIs due to sexual behavior and substance use. HIV PrEP use may increase this risk.
Design:
Our aim was to comparatively assess incident STIs among different at-risk groups—PLWHIV, HIV-negative PrEP and no-PrEP users—seen at our center early after PrEP implementation.
Methods:
Clinical data were retrospectively collected on 636 MSM seen at the Infectious Diseases Department between September 2016 and October 2018. STI incidence rate was assessed among groups for the whole period, as well as separately for each year of the study.
Results:
Overall STI incidence rate ratio was higher in HIV-neg when compared to PLWHIV. In multivariate analysis, STI risk was significantly higher among HIV-neg no-PrEP users compared to PLWHIV, while not different between PLWHIV and PrEP users.
STI incidence globally increased during the first 2 years after PrEP approval among PLWHIV and no-PrEP users, stated by odds ratio (OR = 1.77 [1.23–2.55], p = 0.0020 and OR = 2.29 [0.91–5.73], p = 0.0774 respectively) while it remained rather stable for HIV-neg PrEP users (OR = 1.19 [0.60–2.38], p = 0.6181). The HIV-neg no-PrEP group remained at higher risk of STI than PLWHIV and PrEP users during the two periods.
Conclusion:
These results suggest that a proactive approach of an efficient follow-up of MSM participants since PrEP approval may have prevented an increase of the incidence of STIs among PrEP users
Factors contributing to delays in initiation of front-line cervical cancer therapy: disparities in a diverse south Florida population
Get PDFObjective:
Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation.
Methods:
Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis.
Results:
Of 274 patients studied, the median time to treatment initiation was 60 days (range 0–551). The median times to initiate surgery (54 days, range 3–96) and chemoradiation (58 days, range 4–187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center.
Conclusion:
Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time
Toripalimab combined with concurrent platinum-based Chemoradiotherapy in patients with locally advanced cervical cancer: an open-label, single-arm, phase II trial
Get PDFBackground:
Concurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer.
Methods/design:
The primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival.
Discussion:
PD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study
Combining theory and research to validate a social norms framework addressing female genital mutilation
Get PDFFemale Genital Mutilation (FGM) is a harmful practice with no benefits and considerable harm to girls and women who undergo it. In 2016, the United Nations Joint Program to Eliminate FGM, funded the development and subsequent validation of a monitoring and evaluation framework to understand the relationship between social norms and practicing FGM. Evidence on the framework was gathered through a pilot study in Ethiopia. This paper uses cross-sectional quantitative data from the pilot to operationalize the framework and determine what factors are associated with practicing FGM. A total of 554 and 481 participants answered the question “Have you undergone FGM?” and “Do you know a family member who has undergone FGM?” respectively. Overall, 65% of participants said they had undergone FGM and 32% said they knew someone in their family who had undergone FGM. Predictors of not undergoing FGM included most progressive attitudes vs. less progressive attitudes about FGM and relationship to identity [OR: 1.9 (95% CI: 1.1–3.3)]; region [Afar vs. Addis Ababa: OR: 0.09 (95% CI: 0.02–0.5); Southern Nations Nationalities and People's Regions vs. Addis Ababa: OR: 0.1 (95% CI: 0.05–0.3)], being 36 years old and above vs. 10–19 years (OR: 0.2 (95% CI: 0.1 to 0.7)) and being single, never married vs. married or engaged (OR: 2.8 (95% CI: 1.1–7.0)]. Predictors of knowing a family member who has not undergone FGM included: Higher knowledge vs. lower knowledge [OR: 0.3 (95% CI: 0.1–0.5)]; if the family expected you to abandon FGM, you had a greater odds of knowing a family member who had not undergone FGM [43.6 (95% CI: 2.7–687.8)]; coming from Southern Nations, Nationalities and People's Region was associated with a lower odds of knowing a family member who had not undergone FGM [0.3 (95% CI: 0.1–0.6)]. Being a female influential vs. female caregiver was associated with a higher odds of knowing a family member who had not undergone FGM [2.9 (95% CI: 1.01–5.2)]. This paper has allowed us to validate a theory and research based social norms framework, specifically examining how social and behavior change communication can be used as a mechanism for shifting norms around a given harmful practice. Now that this model has been developed and validated, it is likely to provide a foundation to study the direct and indirect impacts of social norms programming on changing harmful practices, such as FGM
Efficacy and safety of Ashwagandha (withania somnifera) root extract for improvement of sexual health in healthy women: a prospective, randomized, placebo-controlled study
Get PDFBackground:
Poor sexual function is a widespread problem affecting about 40% of women and this may worsen their quality of life. Ashwagandha (Withania somnifera) an adaptogenic herb has been reported to improve sexual satisfaction, sleep, and quality of life in women.
Objective:
The purpose of the study was to evaluate the efficacy and safety of standardized Ashwagandha root extract in improving sexual function in healthy females.
Methods:
In this prospective, randomized, placebo-controlled study, 80 women between 18 and 50 years of age without any hormonal disturbances and having hypoactive sexual desire disorder (HSDD) with a Female Sexual Function Index (FSFI) score 11 were randomized to receive either capsule containing standardized Ashwagandha root extract 300mg twice daily (n=40), or identical placebo (n=40) for eight weeks. Sexual function was assessed using FSFI, FSDS, and Satisfying Sexual Encounters (SSEs). Assessments were done at baseline, four weeks, and eight weeks. Quality of life (QoL) was assessed using the general health questionnaire (GHQ-28) scale, and safety was assessed using clinical signs and symptoms. Repeat measures analysis of variance (ANOVA) was used for the assessment of treatment effect at different time periods. Nominal data were analyzed for differences using Fischer’s Chi-square test.
Results:
There was statistically significant improvement (p<0.0001) in FSFI scores with Ashwagandha [14.20 (0.98) at baseline to 22.62 (2.06) at week 8] as compared to placebo [14.17 (0.71) at baseline to 19.25 (2.23) at eight weeks], and this improvement was observed in all sub-scales (desire, arousal, lubrication, orgasm, sexual satisfaction, and pain) of the FSFI scale. There was a greater improvement (p<0.0001) in FSDS scores with AG as compared to placebo. Although not statistically significant (p, 0.078), there was a greater reduction (improvement) in GHQ-28 scores at eight weeks with Ashwagandha as compared to placebo, and this trend was observed for all domains of GHQ-28 (global, physical, psychological, and social function). More women with Ashwagandha had improvement in SSEs at week 4 (p, 0.017) and week 8 (p, 0.002) as compared to placebo. Adverse events were comparable in the two groups. Two women reported nausea and one reported drowsiness with AG, whereas two reported nausea, one reported drowsiness and one reported nausea with drowsiness in the placebo group.
Conclusions:
Oral administration of Ashwagandha 300mg twice daily administered for eight weeks improves the female sexual health in otherwise healthy women who do not have any hormonal disturbances. Ashwagandha is a known adaptogen, maintains general well-being and improves vitality