Disparities in Breast, Lung, and Cervical Cancer Trials Worldwide

Purpose As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown. Methods We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank. Results Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs ( P < .001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P = .66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work. Conclusion There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences.

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Bevacizumab in Advanced Cervical Cancer: Issues and Challenges for Low- and Middle-Income Countries

Journal of Global Oncology ◽

10.1200/jgo.2016.004895 ◽

2017 ◽

Vol 3 (2) ◽

pp. 93-97 ◽

Cited By ~ 9

Author(s):

Bishal Gyawali ◽

Mahesh Iddawela

Keyword(s):

Cervical Cancer ◽

Cost Effective ◽

Optimal Number ◽

Advanced Cervical Cancer ◽

Cancer Trial ◽

Middle Income ◽

Middle Income Countries ◽

The Status ◽

Number Of Cycles ◽

Low And Middle Income

Bevacizumab became the first molecular antibody to show survival benefit in advanced cervical cancer. In the GOG-0240 (Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer) trial, it improved overall survival by a significant 3.7 months over platinum doublet chemotherapy alone. However, this discovery is not likely to improve the status of global cervical cancer because more than 85% of patients with cervical cancer live in low- and middle-income countries and cannot afford bevacizumab. This commentary looks at the options by which this drug can be made more affordable and cost-effective for patients in low- and middle-income countries. We also discuss other important questions related to its affordability and cost issues such as the optimal number of cycles and personalizing the treatment. Finally, we emphasize that although the unaffordability of bevacizumab in cervical cancer seems to be a very important issue, the best cost-effective strategy against cervical cancer is prevention with screening and vaccination.

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The Development of Priority Cervical Cancer Trials: A Gynecologic Cancer InterGroup Report

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181e730aa ◽

2010 ◽

Vol 20 (6) ◽

pp. 1092-1100 ◽

Cited By ~ 15

Author(s):

Henry Charles Kitchener ◽

William Hoskins ◽

William Small ◽

Gillian M. Thomas ◽

Edward Lloyd Trimble

Keyword(s):

Cervical Cancer ◽

Clinical Trials ◽

Early Stage ◽

Gynecologic Cancer ◽

Good Clinical Practice ◽

Middle Income ◽

Middle Income Countries ◽

Current State ◽

International Participation ◽

Cancer Trials

Since the late 1990s, when a spate of US studies reported the benefit of chemoradiation for cervical cancer, there has been a dearth of clinical trials in cervical cancer. This requires to be addressed with urgency because this disease is responsible for a quarter of a million deaths globally each year, mostly in developing countries, but therapeutic advances are required in all health care settings.The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaborative of leading national groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representations from most of the GCIG groups and selected large centers in low- and middle-income countries. The focus was to identify consensus on several concepts for clinical trials, which would be developed and promoted by the GCIG and launched with major international participation.The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps most needing new evidence. The second half of the meeting was concerned with achieving consensus on the way forward. There were 2 principal outcomes. The first was a proposal to establish, under the umbrella of GCIG, a cervical cancer trials network of centers from countries currently outside GCIG (Eastern Europe, India, Thailand, Southern Africa, and South and Central America), which could increase international participation in trials, conducted within the principles of good clinical practice. The second was to identify the priorities for clinical trials. These included additional systemic therapy before or after chemoradiation; less radical surgery for small, early-stage tumors; the use of fewer fractions to improve cost-effectiveness of treatment in centers with limited resources; and chemotherapy to improve resectability of bulky tumors.

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'Have a Pap smear!' – doctors, their clients, and opportunistic cervical cancer screening

International Journal of STD & AIDS ◽

10.1258/0956462053420266 ◽

2005 ◽

Vol 16 (3) ◽

pp. 233-236 ◽

Cited By ~ 7

Author(s):

L C Chingang ◽

U Bischof ◽

G Andall-Brereton ◽

O Razum

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Pap Smear ◽

Cervical Screening ◽

Pap Test ◽

Community Members ◽

Middle Income ◽

Middle Income Countries ◽

High Incidence

In many middle-income countries with a high incidence of cervical cancer, organized screening programmes with the Pap test are being planned. We assessed the knowledge of, and attitudes towards, cervical screening among 63 doctors and 102 randomly selected community members in Trinidad where screening is still opportunistic. Doctors were well informed about cervical cancer, but not all knew the approximate specificity of the Pap test. Many did not routinely discuss the benefits and disadvantages of screening with their clients. Most women had heard of the Pap test, but only 56% knew its purpose; 25% would not participate in screening, stating reasons such as being in menopause or not having symptoms. More information about the aim of screening and the purpose of the Pap test must be communicated. Doctors need to keep their knowledge on screening up-to-date, and offer counselling that helps women to make an informed decision whether or not to participate in screening.

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Development of HPV 16/18 E6 oncoprotein paper-based nanokit for enhanced detection of HPV 16/18 E6 oncoprotein in cervical cancer screening

10.1101/2020.04.29.20084459 ◽

2020 ◽

Author(s):

Lucy Muthoni Mwai ◽

Mutinda C. Kyama ◽

Caroline W. Ngugi ◽

Edwin Walong

Keyword(s):

Cervical Cancer ◽

Gold Nanoparticles ◽

Cancer Screening ◽

Diagnostic Accuracy ◽

Predictive Value ◽

Intraepithelial Neoplasia ◽

Hpv 16 ◽

Middle Income ◽

Middle Income Countries ◽

E6 Oncoprotein

AbstractCervical cancer caused mainly by high risk human papillomavirus (HPV) 16 and 18 strains is the second most prevalent cancer of women in Kenya. It is often diagnosed late when treatment is difficult due to very low percentage of women attending screening thus, mortalities remain high. The most available tests in low-and-middle-income countries (LMICs) have relatively low specificity, low sensitivity, require a laboratory setting and huge technical and financial support not readily available. HPV 16/18 E6 oncoprotein has been identified as a potential biomarker in a more specific early diagnosis of cervical cancer. This retrospective cross-sectional study developed a paper-based nanokit with enhanced detection of HPV 16/18 E6 oncoprotein for cervical cancer screening. The HRP labelled antibodies HPV 16 E6/18 E6-HRP (CP15) passively conjugated to citrate stabilized 20nm gold nanoparticles were evaluated for immune sensing mechanism using a recombinant viral HPV E6 protein. The diagnostic accuracy was evaluated using 50 tissue lysates from formalin fixed paraffin embedded cervical biopsy, including control (n=10), Mild Dysplasia (n=10), Cervical intraepithelial neoplasia 3 (CIN3) (n=10), Cervical intraepithelial neoplasia 4 (CIN4) (n=10) and invasive carcinoma (n=10). The molecular technique used was dot blot molecular assay. A positive result was generated by catalytic oxidation of peroxidase enzyme on 3,3’,5,5’-Tetramethylbenzidine (TMB) substrate. The gold nanoparticles were used to enhance the signal produced by peroxidase activity of horseradish peroxidase (HRP) enzyme giving a more sensitive assay as compared to use of non-conjugated antibody. This study provides a significantly high and reliable diagnostic accuracy for precancerous and cancerous lesions with a sensitivity of 90%, a specificity of 90%, a likelihood ratio for positive and negative tests as 9:1 and 1:9 respectively, a Positive Predictive Value of 97.3% and a Negative Predictive Value of 69.2%. This study avails a sensitive, rapid test using paper-based nanotechnology which can be utilised in community-based screening outreaches particularly in low- and middle-income countries.

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Human Papillomavirus (HPV)

10.33442/vt202145 ◽

2021 ◽

Author(s):

Anne Schuind

Keyword(s):

Cervical Cancer ◽

Neutralizing Antibodies ◽

Invasive Cervical Cancer ◽

Cancer Control ◽

Middle Income ◽

Middle Income Countries ◽

Common Cancer ◽

Associated Lesions ◽

Hpv Types ◽

E6 And E7

HPV is extremely common worldwide and mainly transmitted through sexual contact; most people are infected with HPV shortly after onset of sexual activity. There are >200 types of HPV, of which at least 12 are cancer-causing (oncogenic or high-risk types). HPV is a causal factor for several anogenital and a subset of oropharyngeal cancers with 2 HPV types (16 and 18) causing 72% of all HPV-associated cancers. Cervical cancer is the fourth most common cancer among women globally with nearly 90% of the deaths occurring in low- and middle-income countries. Comprehensive cervical cancer control includes primary prevention (vaccination against HPV), secondary prevention (screening and treatment of pre-cancerous lesions) as well as treatment of invasive cervical cancer. The currently licensed vaccines are L1 VLP-based and prophylactic; they have been shown to be safe and highly effective in preventing HPV infections and HPV-associated lesions, precancer and cancer. Neutralizing antibodies are the mechanism of protection for prophylactic HPV VLP-based vaccines. Therapeutic HPV vaccines targeting the oncoproteins E6 and E7 are in clinical development.

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Human papillomavirus (HPV) vaccination: from clinical studies to immunization programs

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000582 ◽

2019 ◽

Vol 29 (8) ◽

pp. 1317-1326 ◽

Cited By ~ 6

Author(s):

Raúl Murillo ◽

Camila Ordóñez- Reyes

Keyword(s):

Cervical Cancer ◽

Clinical Trials ◽

Human Papillomavirus ◽

Hpv Vaccine ◽

Hpv Vaccination ◽

Population Based ◽

Immunization Programs ◽

Hpv Vaccines ◽

Middle Income ◽

Middle Income Countries

Cervical cancer incidence and mortality have decreased in high-income countries, but low- and middle-income countries continue to bear a significant burden from the disease. Human papillomavirus (HPV) vaccines are a promising alternative for disease control; however, their introduction is slow in settings with greater need. We conducted a review of HPV vaccine efficacy and effectiveness reported in clinical trials and population-based studies. Efficacy of HPV vaccines is close to 100% when using a three-dose schedule in HPV-negative young women (<25 years old) for protection against persistent infection and HPV vaccine-type associated pre-cancerous lesions. Furthermore, sustained protection for up to 12 years of follow-up has been demonstrated; cross-protection against non-vaccine types is particularly observed for the bivalent vaccine, and preliminary data regarding impact on invasive cancer have emerged. Given its lower efficacy, catch-up vaccination beyond 19 years of age and proposals for vaccinating adult women deserve careful evaluation in accurately designed studies and economic analyses. Despite positive results regarding immunogenicity and post-hoc analysis for cervical intra-epithelial neoplasia in clinical trials, population-based data for prime and booster two-dose schedules are not available. Evaluation of vaccine safety from surveillance systems in immunization programs that have already distributed more than 270 million doses found no association of HPV vaccination with serious side effects. The introduction of HPV vaccination in national immunization programs remains the main challenge in tackling the burden of cervical cancer (up to 2018, only 89 countries have introduced vaccination worldwide, and most of these are high-income countries). Access models and technical capacity require further development to help low- and middle-income countries to increase the pace of vaccine delivery. Alternative approaches such as one-dose schedules and vaccination at younger ages may help reduce the programmatic and economic challenges to adolescent vaccination.

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Implementation of Multicolor Melt Curve Analysis for High-Risk Human Papilloma Virus Detection in Low- and Middle-Income Countries: A Pilot Study for Expanded Cervical Cancer Screening in Honduras

Journal of Global Oncology ◽

10.1200/jgo.17.00035 ◽

2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Scott A. Turner ◽

Sophie J. Deharvengt ◽

Kathleen Doyle Lyons ◽

Jorge Arturo Plata Espinal ◽

Ethan P.M. LaRochelle ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Medical Center ◽

Virus Detection ◽

The United States ◽

Middle Income ◽

Rural Village ◽

Middle Income Countries ◽

Dartmouth Hitchcock Medical ◽

Low And Middle Income

Purpose Cervical cancer is a leading cause of cancer-related mortality in low- and middle-income countries (LMICs) and screening in LMICs is extremely limited. We aimed to implement on-site high-risk human papillomavirus (hrHPV) DNA testing in cohorts of women from an urban factory and from a rural village. Methods A total of 802 women were recruited for this study in partnership with La Liga Contra el Cancer through the establishment of women’s health resource fairs at two locations in Honduras: a textile factory (n = 401) in the city of San Pedro Sula and the rural village of El Rosario (n = 401) in Yoro. Participants received a routine cervical examination during which three sterile cytobrushes were used to collect cervical samples for testing. hrHPV genotyping was performed using a hrHPV genotyping assay and a real-time polymerase chain reaction instrument. Results hrHPV status across all participants at both sites was 13% hrHPV positive and 67% hrHPV negative. When hrHPV status was compared across all three testing sites, hrHPV-positive rates were approximately equal among the factory (13%), village (12%), and confirmatory testing at Dartmouth-Hitchcock Medical Center (Lebanon, NH; 14%). hrHPV genotype was compared across sites, with HPV16 showing the highest infection rate (15%), followed by HPV59 (12%), and HPV68 (11%). There was a low prevalence of HPV18 observed in both populations compared with the hrHPV-positive population in the United States. Conclusion In collaboration with oncologists and pathologists from La Liga Contra el Cancer, we were able to provide a continuum of care once health-fair testing was performed. We established a method and implementation plan for hrHPV testing that is sustainable in LMICs.

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