Role of vaccination in HPV-associated cervical cancer.
\r\n\tThe aim of this book is to provide the reader with a comprehensive state-of-the-art in artificial neural networks, collecting many of the core concepts and cutting-edge application behind neural networks and deep learning.
",isbn:"978-1-83962-375-2",printIsbn:"978-1-83962-374-5",pdfIsbn:"978-1-83962-376-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"5cc6cd7972551be6cfc4d3c87bf8fb5c",bookSignature:"Dr. Pier Luigi Mazzeo and Dr. Paolo Spagnolo",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10390.jpg",keywords:"Recurrent, Recursive Nets, Face Recognition, Crowd Analysis, Different Applications, Object Detection, Classification, Visual Tracking, Speech Recognition, Grams, Reinforcement Learning, 3-D Map",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 25th 2020",dateEndSecondStepPublish:"October 23rd 2020",dateEndThirdStepPublish:"December 22nd 2020",dateEndFourthStepPublish:"March 12th 2021",dateEndFifthStepPublish:"May 11th 2021",remainingDaysToSecondStep:"3 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Author and co-author of more than 80 works in national and international journals, conference proceedings, and book chapters, with Ph.D. in Computer Science Engineering.",coeditorOneBiosketch:"Dr. Spagnolo received the engineering degree in computer science from the University of Lecce, Italy. Since 2002 he has been with the Italian National Research Council. His work includes more than 80 publications on AI.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"17191",title:"Dr.",name:"Pier Luigi",middleName:null,surname:"Mazzeo",slug:"pier-luigi-mazzeo",fullName:"Pier Luigi Mazzeo",profilePictureURL:"https://mts.intechopen.com/storage/users/17191/images/system/17191.jpeg",biography:"Pier Luigi Mazzeo received the engineering degree in computer science from the University of Lecce, Lecce, Italy, in 2001. \nSince 2015 he has been with Institute of Applied Sciences and Intelligent Systems of the Italian National Research Council, Lecce, Italy. The most relevant topics, in which he is currently involved, include algorithms for video object tracking , face detection and recognition, facial expression recognition, deep neural network (CNN) and machine learning.\nHe has taken part in several national and international projects and he acts as a reviewer for several international journals and for some book publishers. He has been regularly invited to take part in the Scientific Committees of national and international conferences. \nDr. Mazzeo is author and co-author of more then 80 works in national and international journals, conference proceedings and book chapters.",institutionString:"Institute of Applied Sciences and Intelligent Systems (CNR)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Institute of Applied Science and Intelligent Systems",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:{id:"20192",title:"Dr.",name:"Paolo",middleName:null,surname:"Spagnolo",slug:"paolo-spagnolo",fullName:"Paolo Spagnolo",profilePictureURL:"https://mts.intechopen.com/storage/users/20192/images/system/20192.jpg",biography:"Paolo Spagnolo received the engineering degree in computer science from the University of Lecce, Lecce, Italy, in 2002.\nSince then he has been with the Italian National Research Council.\nHe has been working on several research topics regarding Artificial Intelligence and Computer Vision studying techniques and methodologies for multidimensional digital signal processing; linear and non-linear signal characterization; signal features extraction; supervised and unsupervised classification of signals; deep neural network (CNN).\nDr. Spagnolo is an author of over 80 papers on Artificial Intelligence. He also acts as a reviewer for several international journals.\nHe has also participated in a number of international projects in the area of image and video analysis and has been regularly invited to take part in the Scientific Committees of national and international conferences.",institutionString:"Institute of Applied Sciences and Intelligent Systems (CNR)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Institute of Applied Science and Intelligent Systems",institutionURL:null,country:{name:"Italy"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"9",title:"Computer and Information Science",slug:"computer-and-information-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"70998",title:"Immunotherapy in Gynecological Malignancies",doi:"10.5772/intechopen.90711",slug:"immunotherapy-in-gynecological-malignancies",body:'\nCancer immunotherapy is emerging as an attractive strategy among different therapeutic options over the past years, and also the treatment of many advanced malignancies has been revolutionized with the development of immune-based antitumor therapies. The advent of targeted immune therapies leading to successful outcomes in other malignancies has led to an increase in the number of clinical trials using these interventional strategies in patients with gynecological cancer. Generally, the role of immunotherapy is either to reactivate the immune response or to diminish the tumor-directed immune inhibition.
\nThere are three stages of the dynamic process of immunoediting, also known as the three Es: an early elimination phase with the activation of an innate and adoptive immune response, an equilibrium phase where the isolated tumor cells are able to endure immune incursion, and an immune escape phase that the cancer cell variants can alter their genomic or antigenic phenotype or they are under the control of immunoregulatory phenomena to survive in the immunosuppressive medium. In order to activate tumor-directed immune responses, recent immune therapies have consisted of several approaches, including adoptive cell transfer (ACT), cancer vaccines, and immune checkpoint inhibitors.
\nCervical cancer is unique among gynecologic malignant tumors because of its well-established and causative risk factor, chronic HPV infection. The infectious etiology of cervical cancer has led to effective vaccines for prevention; however, advanced stage/metastatic disease remains a principal cause of gynecologic cancer mortality in much of the world. The implementation of antiangiogenic therapy has greatly improved the treatment for relapsed/advanced disease over the last 5 years. Several clinical trials including CheckMate 358 and KEYNOTE-028 and KEYNOTE-158 are evaluating the role of immune checkpoint inhibitors in the treatment of cervical cancer.
\nIn endometrial cancer, patients with advanced or disseminated recurrent disease have a poor prognosis, and most patients with peritoneal recurrence are considered incurable. Platinum and taxane chemotherapy produces response rates of 40–60%, which decreases to 20% for second-line drugs. So there is a need for development of more effective treatment for patients having advanced disease.
\nApproximately 25% of endometrial tumors are characterized by defects in the DNA mismatch repair system manifested by errors in DNA replication of trinucleotide repeat regions, commonly referred to as microsatellite instability. These defects in mismatch repair (MMR) also result in a high somatic mutation rate and accordingly increased number of neoantigens in these MMR-deficient tumors. In endometrial cancer, the presence of high microsatellite instability (MSI-H) has become an area of interest for use of immune checkpoint inhibitors.
\nFor several reasons ovarian cancer is an ideal tumor type for which to consider an immunomodulatory management approach. Firstly, there is no negative impact of cancer itself on immunoregulatory cells that may be present within the bone marrow or other body locations. Secondly, while standard cytotoxic therapy of ovarian cancer can result in a depression in the number of immunoregulatory cell, these effects are generally modest in extent and short in duration. Lastly, it is common for patients with ovarian cancer to maintain a quite reasonable performance status and satisfactory nutrition.
\nA majority of ovarian cancer patients respond to cytotoxic chemotherapy and invariably are free from disease for periods varying from months to several years. This time interval can be exploited for required “activation” of immune defense mechanisms, either by using a tested vaccination strategy or any other form of immune modulation.
\nMultiple studies involving immune checkpoint inhibitors, conducted in advanced endometrial cancer, ovarian cancer, and cervical cancer, have shown promising preliminary results. But similar to that seen in other tumor types, continued work will need to focus on identifying those subsets of patients that will benefit from these therapies as these treatments are not without significant toxicities.
\nThe immune system plays an important role in cancer pathogenesis. Numerous clinical trials and multiple researches dedicated to study therapies that involve the immune system to favorably impact the disease course in various malignancies have not only shown improved patient survival but also diversified the whole cancer management scenario by approval of the use of various immunotherapeutic agents in advanced malignancies [1].
\nSince cancer immunotherapy has emerged as an effective and appealing therapeutic option among other different therapeutic strategies and has been proven competent against multiple malignancies, it has led to an increase in research on immunomodulatory approaches in gynecological malignancies [2].
\nThe ongoing research on the understanding of tumor biology and immunology has led to improved comprehension of mechanisms of immune recognition, regulation, and tumor escape that has provided new approaches for cancer immunotherapy [3].
\nThe principal role of the immune system is against foreign pathogens and infections. It is further classified as cellular and humoral immune systems, mediated by T and B lymphocytes and their products, respectively.
\nThe initial innate immunity is nonspecific, and the adaptive immune response is the specialized defense. Both the strategies work in different manner. They employ the cellular immunity which has a rather fast response in eradicating intracellular microbes through the recognition of antigens, activation of antigen-presenting cells (APCs), and activation and proliferation of T cells. They also need humoral immunity mediated via antibodies produced by B cells for neutralizing toxins and act against infections. Where innate immunity works by releasing signals essential to stimulate responses from both T cells and B cells [4], the adaptive immune system is mainly consists of B cells, CD8+ cytotoxic T cells, as well as CD4+ helper T cell [5].
\nThe immune system in tumor cells has a dynamic relationship, in which either it can identify or control tumor cells in a process called cancer immunosurveillance or cause tumor progression through chronic inflammation, immunoselection of poorly immunogenic variants, and suppressing antitumor immunity [6]. There are three stages of this dynamic process called immunoediting. The first is the elimination phase in which innate and adaptive immunity works together to identify and eliminate the cancer cells before they become clinically apparent [7]. If the cancer cells are not eliminated, they enter the second phase which is equilibrium. It can last from months to years. Here the cancer cells persist, but outgrowth is prevented by the immune system. Lastly the escape phase is in which either the cancer cell variants survive in the immunosuppressive microenvironment by altering genetic or antigenic phenotype or under the control of immunoregulatory phenomena. [8] In order to activate tumor-directed immune responses, recent immune therapies have consisted of several approaches, including adoptive cell transfer (ACT), cancer vaccines, and immune checkpoint inhibitors.
\nGynecological cancers are a group of malignancies that involve different organs that comprise the female reproductive system. The most common types of gynecologic malignancies are cervical cancer, ovarian cancer, and endometrial cancer. Other less common gynecological malignancies arise from the vagina, vulva, and fallopian tubes [9].
\nCervical cancer represents 6.6% of all female cancers. It is the fourth most common cancer in women with an estimated 570,000 new cases in 2018. Approximately 90% of deaths from cervical cancer occur in underdeveloped and developing countries [10]. Cervical cancer has emerged as a preventable disease due to currently employed screening tests which have highlighted HPV infection as an etiological factor. Although significant progress has been made in screening and prevention of cervical cancer, the 5-year overall survival remains 66% [11]. For cases diagnosed at an early stage, the recurrence rates vary between 10 and 20%, but for advanced cases, the rate of recurrence reaches up to 70% [12]. There is a need to improve outcomes, and immunotherapy could offer this possibility. The recognition of human papilloma virus as an etiological agent has greatly improved the understanding of the disease and led to improved strategies in prevention of cervical cancer [13]. The infectious etiology of cervical cancer has led to effective vaccines for prevention; however, advanced stage/metastatic disease remains a principal cause of gynecologic cancer mortality. Currently there are three licensed HPV prophylactic vaccines, namely, bivalent vaccine cervarix against HPV16/18, Gardasil against HPV-6/11/16/18, and Gardasil9, a nonavalent HPV-6/11/16/18/31/33/45/52/58 vaccine. All are based on on-infectious recombinant type-specific L1 capsid proteins assembled into viral-like particles (VLPs) as immunogens [14].
\nThere is a huge unmet need for the treatment for women having advanced/recurrent cancer after standard chemotherapy and immunotherapy aims to fill that void, through therapies that harness a patient’s own immune system to attack the cancer.
\nCancer vaccines are used to mediate immune response by activating T cells which can specifically recognize cancer cells by tagging them with tumor-specific antigens E6 and E7. These antigen-tagged tumor cells are recognized by antigen-presenting cells and killed by cytotoxic T cells [15].
\nLive vector vaccines are highly immunogenic vaccines which can stimulate mucosal as well as humoral and/or cellular systemic immunity. They present E6 and E7 to APC to cause immune response through major histocompatibility complex MHC I [16]. Although they are attenuated vaccines, still care has to be taken before administering it in immunocompromised individuals. ADXS11-001 is a type of live attenuated vaccine that uses Listeria monocytogenes (Lm), a gram-positive intracellular bacterium as bacterial vector. It secretes HPV-16 E7 antigen fused to a nonhemolytic fragment of Lm protein listeriolysin O [17].
\nThe following studies have been conducted (\nTable 1\n):
\nRefer \nTable 2\n.
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Maciag et al. [18] Phase I trial | \n\nn = 15 Recurrent or metastatic disease | \nDL1: ADXS11-001 1 × 109 two doses every 21 days DL2: ADXS11-001 3.3 × 109 two doses every 21 days DL3: ADXS11-001 1 × 1010 two doses every 21 days | \nStable disease in 7 patients | \nPyrexia (100%), vomiting 60%, pain (57%), chills, anemia (53%) Grade 3: 40% (6 pts) | \n
Ghamande et al. [19] Phase I | \n\nn = 9 Recurrent or metastatic disease | \nDL1: ADXS11-001 5 × 109 thrice weekly during 12 weeks DL2: ADXS11-001 1 × 1010 thrice weekly during 12 weeks | \n— | \nTRAE: 75% AE: 99% Grade 1 and 2 Grade 3: chills, vomit, hypotension, tachycardia, fever, and nausea | \n
Basu et al. [20] Phase II | \n\nn = 109 Advanced cervical cancer | \nArm 1 ADXS11-001 monotherapy Arm 2 ADXS11-001 with cisplatin combination | \nMedian progression-free survival (6.10 vs. 6.08 months) and the overall response rate (17.1% vs. 14.7%) were similar for both groups | \nMore adverse effects in arm 2 | \n
Huh et al. [21] (GOG 0265) Phase II | \n\nn = 26 Recurrent or metastatic disease | \nADXS11-001 1 × 109 every 28 days for 3 doses | \nMean 12 months survival: 38.5% Median OS: 6.2 months | \nAE: 91% Grade 1 and 2 TRAE: 38%: nausea, vomiting, chills, fatigue, and fever | \n
Role of vaccination in HPV-associated cervical cancer.
Study name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Welters et al. [22] Phase II adjuvant | \n\nn = 6 Stage IB1 and HPV16+ | \nHPV16 E6 E7 SLP vaccine | \nVaccine-enhanced number and activity of HPV16-specific CD4+ and CD8+ cells | \nGrade 1 and Grade 2: local pain, fever, flu-like symptoms, swelling, itching, burning eyes | \n
Poelgeest et al. [23] Phase II | \n\nn = 31 Recurrent or metastatic disease | \nHPV16 E6-E7 SLP vaccine 300 g for four doses every 21 day | \nMedian OS: 12.6 months no tumor regression or delay of progression | \nGrade 1 and Grade 2: fever, fatigue, headache, flu-like symptoms, chills, nausea, swelling extremities, rash, vomiting, tingling extremities, and injection site pain | \n
Peptide-based vaccine in cervical cancer.
Refer \nTable 3\n.
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Ramanathan et al. [24] Phase I | \n\nn = 14 Recurrent or metastatic disease | \nArm 1: placebo three doses every 14 days Arm 2: unprimed DC three doses 1 × 106 cells every 14 days Arm 3: primed DC three doses 1 × 106 cells every 14 days | \nSD in Arm 3 | \nGrade 1 and Grade 2: itching at injection site, fever, chills, abdominal discomfort, vomit, ALP increased | \n
Ferrara et al. [25] Phase I | \n\nn = 15 Recurrent or metastatic disease | \nAnalogous dendritic cells pulsed with HPV E7 protein | \nSerological response in 3 pts Cellular response in 4 pts No objective clinical response | \n\n |
Santin et al. [26] Phase I | \n\nn = 10 Stage IB or IIA | \nDL1: HPV16/18 E7 antigen-pulsed DC5 × 106 for five doses every 21 days DL2: HPV16/18 E7 antigen-pulsed DC10 × 106 for five doses every 21 days DL3: HPV16/18 E7 antigen-pulsed DC15 × 106 for five doses every 21 days | \nCD4+ T-cell response in all patients | \nMild swelling and erythema at the injection site | \n
Dendritic vaccine in cervical cancer.
Programmed cell death protein-1/programmed death ligand-1 immunoregulatory axis is a promising target for cervical cancer treatment [27]. Pembrolizumab is a humanized monoclonal immunoglobulin G4 (IgG4) kappa isotype antibody targeting PD-1 (\nTable 4\n).
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
\nKeynote 028\n Frenel et al. [28] Phase Ib | \n\nn = 24 Patients having metastatic disease in PD L1 > =1% | \nPembrolizumab 10 mg/kg every 2 weeks up to 2 years | \nORR = 12.5% 6 months PFS 13% OS 66.7% (preliminary results) | \n75% pts with treatment-related adverse effects 20.8% with Grade 3 toxicity | \n
\nKeynote 0158\n Schellens et al. [29] Phase II | \n\nn = 47 Metastatic disease | \nPembrolizumab 200 mg thrice weekly to 2 years | \nORR 17% (independent of tumor PD L1 status) | \nNot reported | \n
PD1/PDL1 inhibitors in cervical cancer.
Other ongoing trials of pembrolizumab include PAPAYA Trial [30] which is a phase I study involving Stage Ib to Stage IV cervical cancer. The treatment schedule includes intravenous pembrolizumab followed by cisplatin-based chemoradiotherapy and brachytherapy and additional pembrolizumab after radiation. Another phase II trial with pembrolizumab followed by chemoradiotherapy and brachytherapy is also open for recruitment [31].
\nNivolumab is a human IgG4 monoclonal antibody that causes stimulation of PD1 pathway-mediated immune response inhibition by binding to the PD-1 receptor and blocking its interaction with PD-L1 and PD-L2. [32] Checkmate 358 trial is a phase I/II trial by Hollebecque et al. in 19 patients of cervical cancer which studied nivolumab 240 mg every 2 weeks and showed ORR was 20.8% and disease control rate was 70.8%. Responses were observed regardless of PD-L1 expression, HPV status, and number of prior therapies [33].
\nOther trials of nivolumab include NRG-GY002, a phase II trial in recurrent or metastatic breast cancer [34]. A trial of nivolumab with HPV 16 SLp vaccine in HPV 16 positive cervical cancer is also underway [35].
\nOther checkpoint inhibitors under investigation include atezolizumab which is a fully humanized monoclonal antibody IgG1 isotype PD-L1. It is being studied to assess the safety and efficacy in combination with cyclophosphamide/carboplatin in gynecological cancer including cervical cancer in phase Ib PRO-LOG study [36]. Another phase II study is ongoing to study the synergistic action of antiangiogenic therapy with immunotherapy by combining bevacizumab with atezolizumab in women with recurrent or metastatic cervical cancer [37, 38],
\nDurvalumab is a human IgG1 monoclonal antibody that blocks the action of PD-L1 with PD1 and CD 80. It is being studied along with tremelimumab, which is an antibody against CTLA4 in patients who have failed to respond or relapsed to standard treatment [39].
\nIpilimumab is a fully human monoclonal IgG1κ antibody which acts against the cytotoxic T lymphocyte antigen-4 (CTLA-4). CTLA4 is an immune-inhibitory molecule which is expressed in activated T cells and in suppressor T regulatory cells [40] (\nTable 5\n).
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Lheureux et al. [41] Phase I/II | \n\nn = 42 Recurrent or metastatic disease | \nPhase I: ipilimumab 3 mg/kg every 21 days for four doses Phase II: ipilimumab 10 mg/kg every 21 days for four doses and four cycles (same dose) every 12 weeks | \nMedian PFS 2.5 months | \nGrade 3 toxicity: diarrhea, colitis | \n
GOG9929 study Mayadev et al. [42] Phase I | \n\nn = 34 FIGO IB2/IIA or IIB/IIIB/IVA, positive nodes | \nWeekly cisplatin 40 mg/m2 during 6 weeks and extended field radiotherapy. If no progression 2–6 weeks after DL1: ipilimumab 3 mg/kg for four doses every 21 days DL2: ipilimumab 10 mg/kg for four doses every 21 days DL3: ipilimumab 10 mg/kg for four doses every 21 days | \n1 year DFS 74% | \nGrade 1 and Grade 2: rash, endocrinopaties, gastrointestinal toxicity Grade 3: 16% including lipase increased, neutropenia, and rash | \n
CTLA4 inhibitors in cervical cancer.
Adoptive cell transfer therapy using autologous tumor-infiltrating lymphocytes is emerging as a promising treatment modality in immunotherapy for various cancers. There are two types of adoptive cell therapy which includes chimeric antigen receptor T-cell (CAR T-cell) therapy and tumor-infiltrating lymphocyte (TIL) therapy.
\nChimeric antigen receptor (CAR) T-cell therapy involves genetically engineered patient’s autologous T cells that causes them to express a CAR specific for a tumor antigen. These cells are extracted, further divided, and reinfused back into the patient [43].
\nA trial was conducted by Lu et al. which evaluated adoptive CD4+ T-cell therapy in solid metastatic cancer. It had two patients of metastatic cervical cancer, out of which one patient had objective complete response [44].
\nThere is a trial ongoing to test the safety, feasibility, and efficacy of CAR T-cell immunotherapy in patients who have GD@, PSMA, Muc1, mesothelin, or positive cervical cancer markers by Chang et al. [45].
\nTIL therapy predates the CAR T-cell therapy, and the basic principle involves the ex vivo culture of tumor specimens which have been resected and expansion of tumor-infiltrating lymphocytes (TILs) with interleukin-2. Selected T cells of a preferred antigen specificity and phenotype can be identified in vitro and divided. The number of antigen-specific T cells in peripheral blood after this method usually exceeds by far that possible by current vaccine treatment strategies alone. In addition, adoptive T cells appear more effective in inducing tumor regression than lymphocytes generated by vaccines, suggesting greater ability to overcome tumor-mediated immune evasion mechanisms [46].
\nStevanovic et al. [47] conducted a trial on 17 patients of metastatic cervical cancer who received high-dose lymphocyte-depleting chemotherapy followed by aldesleukin. Patients were treated with a single infusion of human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Three of nine patients experienced objective tumor responses (two complete responses and one partial response).
\nEndometrial cancer is the 4th most commonly occurring cancer in women and the 15th most commonly occurring cancer overall. There were over 380,000 new cases in 2018 [48]. In women with advanced and recurrent cancer, the prognosis is considered very poor. Unfortunately, there are limited treatment options for advanced or recurrent endometrioid endometrial cancer. However, with the advent of immunotherapy, immune checkpoint inhibitors have shown promising results in these cases. Microsatellite instability-high (MSI-H) status, tumor mutation burden, and high PD-L1 expression have been associated with higher response rates to this therapy [49].
\nApproximately 25% of endometrial cancer show microsatellite instability which is caused by defects in mismatch repair genes. These defective MMR genes lead to high somatic mutation rates, thereby increasing the number of neoantigens in MMR-deficient tumors [50].
\nEndometrial cancer has been subdivided into four prognostically distinct molecular subgroups based on the findings of the cancer genome atlas, namely, polymerase epsilon (POLE) ultramutated, MSI hypermutated, copy-number (CN) low, and CN high [51].
\nThe ultramutated POLE subgroup and MSI hypermutated subgroup have immune-rich microenvironment and high mutation load. Evidence has supported over-expression of the PD-1/PD-L1 pathway in these molecular subtypes, and therefore, PD1/PD L1-targeted immunotherapy has a role in these tumors [52] (\nTable 6\n).
\nAn ongoing phase II, two group trials are studying the role of avelumab in POLE-mutated endometrial cancer and MSS-mutated endometrial cancer. Avelumab is administered at 10 mg/kg as 1-hour IV infusion every 2 weeks until disease progression or unacceptable toxicity. Sixteen patients are enrolled in each cohort in the first stage. The preliminary results are yet to be published [57].
\nThe following studies have been conducted (\nTable 7\n).
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Ott et al. [53] | \n\nn = 24 Locally advanced or metastatic PD-L1-positive endometrial cancer | \nPembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity | \nThree (13%) patients achieved confirmed partial response. Three additional patients achieved stable disease, with a median duration of 24.6 weeks | \nGrade 3 treatment-related AEs were reported in four patients | \n
Makker et al. [54] Phase II | \n\nn = 53 Metastatic endometrial cancer unselected for microsatellite instability or PD-L1 | \n20 mg oral lenvatinib daily plus 200 mg intravenous pembrolizumab every 3 weeks, until progression or unacceptable toxicity | \nPatients had an objective response at week 24 | \nSerious treatment-related adverse events occurred in 16 (30%) patients, and one treatment-related death was reported (intracranial hemorrhage) | \n
Santin et al. [55] | \n\nn = 2 Pretreated polymerase ε (POLE) ultramutated and MSH6 hypermutated recurrent endometrial tumors refractory to surgery, radiation, and chemotherapy | \nAnti-PD1 immune checkpoint inhibitor nivolumab 3 mg/kg biweekly | \nBoth patients demonstrated a remarkable clinical response to the anti-PD1 immune checkpoint inhibitor nivolumab | \nNo Grade 3 or higher side effects reported | \n
Fleming et al. [56] | \n\nn = 15 Previously treated recurrent endometrial cancer | \nAtezolizumab 1200 mg or 15 mg/kg IV q3w was administered until toxicity or loss of clinical benefit | \nORR was 13% (2/15) Of the remaining pts, two had SD, nine had PD, and two were non-evaluable | \nSeven (47%) pts had any related AE, mainly G1-2 (5 pts). No G4-5-related AEs occurred | \n
Immunotherapy in endometrial cancer.
Study name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Ohno et al. [58], phase II | \n\nn = 12 WT1/human leukocyte antigen (HLA)-A*2402-positive gynecological cancer | \nIntradermal injections of a HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks | \nStable disease in three patients and progressive disease in nine patients. The disease control rate was 25.0% | \nLocal erythema occurred at the WT1 vaccine injection site | \n
Coosemans et al. [59] | \n\nn = 6 Pretreated patients with uterine cancer | \nFour times weekly vaccines of autologous dendritic cells (DCs) electroporated with WT1 mRNA | \nThree out of four human leucocyte antigen-A2 (HLA-A2)-positive patients showed an oncological response. Two HLA-A2-negative patients did not show an oncological or an immunological response | \nOne patient had a local allergic reaction | \n
Anticancer vaccines in endometrial cancer.
Ovarian cancer accounts for 2.5% of all malignancies among females but 5% of female cancer deaths because of low survival rates, largely driven by late-stage diagnoses [60]. There were nearly 300,000 new cases in 2018. Ovarian cancer is considered to be an ideal type of tumor which can be dealt with immunomodulatory approach as the disease does not negatively affect the immunoregulatory cells in the bone marrow or other locations of the body, and the patients suffering from ovarian cancer maintain a relatively good performance status even in later stages, so immunotherapy can be used as a potential treatment option in these patients. Cytotoxic chemotherapy given in ovarian cancer can negatively impact the immunoregulatory cells, but the effect is short lasting. Further the patients who are in advanced stages, if they respond to standard treatment of ovarian cancer, have a relatively long disease-free period which is substantial for the activation of immune defense mechanism either by cancer vaccines or by immunomodulator drugs [61].
\nThe first published data supporting checkpoint inhibitors as a potentially valuable therapeutic option in ovarian cancer were observed in the trials of the anti-PD-1 antibody nivolumab and the anti-PD-L1 antibody BMS-93655 [62]. Other studies are as follows (\nTable 8\n).
\nStudy name | \nPatient cohort | \nTreatment schedule | \nResponse | \nToxicity | \n
---|---|---|---|---|
Hamanishi et al. [63] Phase II | \n\nn = 20 Platinum-resistant ovarian cancer | \nIV nivolumab every 2 weeks at a dose of 1 or 3 mg/kg | \nOverall response rate was 15%, and the disease control rate was 45% | \nGrade 3 or 4 TRAE in 40% patients | \n
Disis et al. [64] Phase Ib | \n\nn = 124 Recurrent/refractory ovarian cancer | \nAvelumab 10 mg/kg IV every 2 weeks | \nORR was 9.7% based on 12 partial responses; 6 were ongoing. Stable disease was observed in 55 pts (44.4%); disease control rate was 54.0% | \nGrade 3 or 4 TRAEs were reported in 6.5% | \n
Varga et al. [65] Phase Ib | \n\nn = 26 Advanced ovarian cancer | \nPembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity | \nThe best overall (confirmed) response was 11.5%. 6/26 (23.1%) had evidence of tumor reduction; 3 had a tumor reduction of at least 30% | \nDrug-related AEs occurred in 69.2% of pts | \n
Lee et al. [66] Phase I/II | \n\nn = 12 BRCA positive with ovarian cancer | \nDurvalumab at 1500 mg every 4 weeks plus olaparib at 300 mg twice daily and durvalumab at 1500 mg every 4 weeks plus cediranib at 20 mg 5 days on/2 days off per week | \nORR of 17% and disease control rate of 83% | \nGrade 3 or 4 TRAEs were reported in 75% patients | \n
Immune checkpoint inhibitors in ovarian cancer.
Ongoing trials include JAVELIN Ovarian 200 is the first phase III trial, which is a three-arm trial, comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian cancer [67].
\nNCT02839707 is undergoing trial which is comparing pegylated liposomal doxorubicin with atezolizumab and/or bevacizumab in refractory ovarian cancer [68].
\nA phase II study by Wenham et al. [69] is studying combination of weekly paclitaxel and an anti-PD-1 (pembrolizumab). The primary endpoint of this study is a 6-month progression-free survival rate.
\nATALANTE trial is an ongoing phase III study to assess the efficacy of atezolizumab in combination with platinum-based chemotherapy plus bevacizumab administered concurrent to chemotherapy and in maintenance [70].
\nCheckMate 032 study trial to study the safety and efficacy of nivolumab as a single agent or in combination with ipilimumab is currently underway [71].
\nSimilar trial in which nivolumab with or without ipilimumab in treating patients with persistent or recurrent epithelial ovarian is being studied by the National Cancer Institute [72].
\nA phase II trial to determine the median immune-related progression-free survival (irPFS) in combination of an anti-CTLA-4 antibody (tremelimumab) with an anti-PD-L1 antibody (durvalumab) versus their sequential use in platinum-resistant epithelial ovarian cancer is also currently ongoing [73].
\nMultiple other trial are using immune checkpoint inhibitors in initial therapy to improve progression-free survival like durvalumab or pembrolizumab with standard paclitaxel and carboplatin therapy, where pembrolizumab is used as adjuvant therapy after surgery [74]. The role of immune checkpoint inhibitors as maintenance therapy is also under investigation with JAVELIN Ovarian 100 phase II study of avelumab (anti-PD-L1) as maintenance after standard therapy or in combination with standard therapy and then continued as maintenance treatment [75].
\nVarious types of cancer vaccines are studied for the treatment of ovarian cancer.
\nThe cancer testis antigen, NY ESO1, is most frequently expressed in epithelial ovarian cancer, and vaccine against it has shown induced T-cell-specific immunogenicity [76]. Since NY-ESO-1 is regulated by DNA methylation, it was hypothesized that DNA methyltransferase (DNMT) inhibitors may augment NY-ESO-1 vaccine therapy. Decitabine is a hypomethylating agent that inhibits DNA methyltransferase. A phase I trial was conducted to study dose escalation of decitabine in addition to NY-ESO-1 vaccine and doxorubicin liposome in 12 patients with relapsed epithelial ovarian carcinoma. The results showed stable disease or partial response in six patients [77].
\nSabbatini et al. conducted a phase I trial in 28 patients which showed that in order to enhance the immunogenic response to NY-ESO1, the addition of immune modulation agents to the vaccine preparation such as Montanide and immunostimulants such as the toll-like receptor (TLR) ligand poly-ICLC (polyinosinic-polycytidylic acid—stabilized by lysine and carboxymethylcellulose) can be considered [78].
\nOther antigen under investigation is Her/neu2, which is expressed in 90% of epithelial ovarian cancers. A phase I/II study conducted BY Chu et al. demonstrated a 90% 3-year overall survival response in patients with advanced ovarian cancer who were remission for vaccination with monocyte-derived dendritic cells (DC) loaded with Her2/neu, hTERT, and PADRE peptides, with or without low-dose intravenous cyclophosphamide [79].
\nIn a phase I/II study by Baek et al., 10 ovarian cancer patients with minimal residual disease were treated with dendritic cell vaccination with IL2. Three out of 10 patients showed maintenance of complete response, and one patient showed stable disease [80].
\nA phase II study was conducted to study the efficacy of personalized peptide vaccine (PPV) for recurrent ovarian cancer patients by Kawano et al. [81]. The patients enrolled in this study showed an overall survival (OS) of 39.3 months in platinum-sensitive cases and 16.2 months in platinum-resistant cases. This was attributed to be secondary to the stabilization of disease and the prolongation of tumor progression rather than disease regression.
\nAdoptive cell transfer therapy is not widely studied in ovarian cancers. In a Japanese study by Fujita et al., 13 patients with epithelial ovarian cancer were treated with tumor-infiltrating lymphocyte therapy. Eleven patients served as control group who received only chemotherapy following primary operation. The estimated 3-year overall survival rate of disease-free patients in the TIL group and in the control group was 100 and 67.5%, respectively [82].
\nVulvar and vaginal cancer: Immunotherapy has shown promising results in advanced gynecological cancer. Checkmate 358 trial has shown that nivolumab has encouraging clinical activity in cases of HPV-positive vulvar and vaginal malignancies. A lot of research is warranted to establish immunotherapy as emerging treatment option in these cancers.
\nImmunotherapy is emerging as a viable treatment modality in multiple cancers, and its safety and efficacy are under investigation in advanced gynecological malignancies. Immune checkpoint inhibitors have shown promising preliminary results in advanced ovarian, cervical, and endometrial cancer.
\nSince the end of the Cold War and the dissolution of the former Union of Soviet Socialist Republic (USSR) in 1991, Africa as a region has undergone a major structural transformation in social, political, demographic, and economic spheres. In political sphere, the region has gone from a one-party state governance to a multiparty democratic system ([1], p. 300). In social sphere, social governance is slowly but steadily being shared by the rising civil society and the NGOs that have now become copartners at addressing and debating social, economic, and political challenges in Africa. In demographic sphere, the region has seen a twofold increase in its population growth in the last quarter century. And finally, as regards to the economic sphere, whether voluntarily or involuntarily, since the 1990s, Africa has become a full participant in the economic and commercial globalization spurred by the West and led by the United States. And because of the abovementioned structural transformation of the continent, the region has nonetheless grown economically and registered stellar economic numbers in the last decades or so. That is, through the decade of the 2000s to the year 2013, for instance, the global boom in commodity prices propelled natural resources and oil- and gas-exporting African countries to register incredible economic growth and empower Africa into the twenty-first-century global economy [2]. As a result, Africa as a region is now a full member of the world economy and a coveted actor in the international economic arena.
However, despite the impressive recorded economic growth mainly by the energy and commodity-exporting African countries as stated above, as a region, Africa is still facing serious local and transnational challenges such as youth unemployment, climate change threats, rapid population growth, undernourishment, domestic terrorism, drug trafficking, maritime piracy, protracted political crises and low-intensity short-lived wars, and conflict-induced famines like the one we are witnessing in South Sudan today. Consequently, those challenges stand in the way against Africa’s pursuit to achieve food security and eradicate hunger.1 Therefore, if these above-cited challenges are not properly addressed and seriously tackled by the African political leadership, it is probably fair to say that achieving food security and meeting nutrition needs and targets as established by the Millennium Development Goals (MDGs) (2000–2015) and Sustainable Development Goals (SDGs) (2015–2030) will simply be another elusive quest for Africa among many other policy objectives and goals. In addition, if that happens to be so, the continent will unfortunately continue to languish behind other regions of the world in socioeconomic and human developments.2 And consequently, it will be nowhere near attaining the SDG goals and targets just as it failed to meet the past MDG goals and targets. As a case in point, despite its modest registered economic growth and well-intentioned international policy initiatives such as the cited MDGs and SDGs aimed at fighting hunger and overcoming nutrition deficits [4] among many other human and development policy objectives, only few African countries managed to meet the MDGs 1c [5]. With that being said, this chapter sets out to present the state of Africa’s food insecurity and nutrition deficits and addresses the potential impacts of the above-cited challenges, widely regarded today as the real barriers against successful eradication of food hunger and achieving food security in sub-Saharan Africa.
In this chapter, we use the definition of food security as stated by the United Nations Food and Agriculture Organization (UNFAO). The FAO’s definition is our guiding principle and upon which our analysis of Africa’s food security challenges is based. The FAO defines food security as “When all people, at all times, have physical, social and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life [6].” Nonetheless, achieving food security however requires that:
Sufficient quantities of appropriate foods are consistently available.
Individuals have adequate incomes or other resources to purchase or barter for food.
Food is properly processed and stored.
Individuals have sound knowledge of nutrition and child care that they put to good use and have access to adequate health and sanitation services [7].
To begin with, it is worth pointing out from the onset that food insecurity is a multidimensional problem. It is a problem that is linked to healthcare, conflicts, policies, politics, leadership, strategic vision, trade and economic interests, agricultural production, food system, global food industry trade politics, and the environment (mother nature). As an example, in the sphere of healthcare, one can see a direct link between food insecurity, malnutrition, and a global pandemic like the HIV/AIDS. That is to say, if a member of a given family, for instance, is affected by the AIDS epidemic, the family of that patient will automatically lose a breadwinner and financial income generator. That is, the person affected by the disease will no longer be able to engage in any remunerative physical activity whether for themselves or for a third party in order to earn a living. Consequently, he or she will financially no longer contribute to his or her family well-being since they will not be able to generate any income whatsoever. And if and when that situation were to occur, the family of the patient in question would begin to eat less. The body of the affected person will by then have become vulnerable and weak to engage in any remunerative activity. As a result, food insecurity will then have set in, and poverty trap will have taken over and affected everyone within that family.
At the time of writing this chapter, Africa’s state of food insecurity relative to other regions of the world, except for West Asia, is troubling and non-promising. Hence, understanding and accepting this reality should be of a concern for all Africans regardless of their socioeconomic and political status. That is to say, this said reality should be of a concern for the African political leadership, the mayors of mega African cities,3 the NGOs, the civil society, the media, the farmers, the business community, the youth, the academia, the churches, the mosques and other faith-based organizations, and the consumer organizations alike. And according to the FAO 2015 State of Food Insecurity in the World IN BRIEF, Africa scores poorly in all indicators regarding food security and nutrition targets. For example, in 2015, only 18 out of 54 African countries have reached the MDG 1C hunger target (Millennium Development Goals 1C).
Furthermore, two of the many reasons why food security keeps evading millions of Africans are the never-ending conflicts and incessant political instability on the continent. Often, in many sub-Saharan African countries, foods are available and plentiful but not accessible to everyone. Poor families, for example, disproportionately pay the brunt of conflicts and wars. Farmers cannot bring their staple crops to the markets because of the lack of security even if and when they wanted to do so. Put it simply, conflicts disrupt markets and affect development policies that are put in place to assist the neediest of the population. And as a consequence of conflicts and wars, food prices rise, and poor families and their children can no longer have access to healthy and balanced dietary foods (utilization). Conflicts make food production drop since no one will risk their lives to work in the fields and bring foods to the markets while killings are raging. In the Central African Republic, for instance, the short-lived war of 2013 and its aftermath caused a drastic reduction in food production (availability) and engendered the rise of food commodity prices (accessibility). In fact, poor families and anyone else who could not have access to the foods in the markets were simply forced to live in subsistence. Consequently, thousands of Central Africans became nutrition-challenged because whatever was available for them to eat was obviously not meeting their nutrition needs and targets. Furthermore, widespread insecurity across the entire country made it more difficult to import foods from the neighboring countries or even receive foods from aid donors and the international community (stability) for that matter. As a result, food insecurity, and in many instances, the lack of foods thereof, became the daily reality of untold Central African families. And additionally, this added existential threat exacerbated an already desperate and deteriorating economic condition caused by years of protracted conflicts and political and economic mismanagement [9].
There are a lot of reasons as to why Africa and sub-Saharan Africa in particular is suffering from food insecurity and failing to meet its nutrition needs and targets. Though it is true that one cannot put their fingers at one specific reason as for why food shortages, insecurity, and prevalence of malnutrition uninterruptedly afflict sub-Saharan Africa, one can however identify a number of failed internal economic policy tools and international policy prescriptions as the culprit or underlying causes of systemic food insecurity in Africa. That is to say, on the internal front, for example, fewer among many reasons as for why food insecurity has been chronic in many African countries are the following: (1) the never-ending political instability and crises; (2) the short or long protracted civil conflicts and wars; (3) the endemic, persistent, and institutional corruption; (4) the misdirected economic policies and mismanagement; (5) the lack of committed political leadership; (6) the sheer neglect towards the farmers; and (7) the lack of clear financial and economic investment into the agricultural sector. On the external front, however, economic policy prescriptions mainly written and formulated by the World Bank (WB) and the International Monetary Fund (IMF) in the 1970s, 1980s, and the latter part of the 1990s directed at the African countries made an already difficult economic situation worse. This is because the architects of the alluded policies advised sub-Saharan African governments and leaders to cut aid and slash subsidies to their farmers. The economic policy rationale was that African countries should pull the plug under their parastatals (government-owned enterprises) and let the markets take care of everything. In addition, respective African governments were told that Africa should privatize and liberalize their economic policies in order to align them with the prevailing international trade, investment, and economic principles. Those economic recipes were said to modernize Africa and speed up its incorporation into the liberal-based global market economy. Consequently, because of those policy prescriptions, African farmers lost income supports from their respective governments, and millions of low-income African families became victims of food insecurity and nutrition deficits. In essence, the IMF and the World Bank, and to a certain extent the US Treasury Department promoting and owning the so-called Washington Consensus, should be held responsible for those failed policies. For, they were the ones that devised, concocted, and directed them. As a matter of fact, they actively promoted or better said imposed them upon weak and hopeless African governments. And in turn, hapless African leaders implemented the said policies without truly understanding their future potential consequences on the farmers and their societies at large ([10], pp. 369–370).
So, with the benefit of hindsight today, one can say that those structural adjustment programs (SAPs) as they were known then, and devised by the above-cited international institutions and encouraged by the US Treasury Department, contributed to the demise of many farmers in Africa. They exacerbated the food insecurity and the existing precarious economic plights of millions of African families. And with the passing years, it has now become clear to any astute observer of the recent history of the social and economic development of Africa that African leaders of that time were not wise enough to reject and outrightly oppose those policies [9]. Actually, in fairness, many of them heartily and readily adopted the said policies and imposed them on their beleaguered poor populations. In fact, soon after they did so, many African countries began to import foods in huge quantity. And unfortunately, this situation has now lingered for decades. And honestly, as of today, there is no end in sight as to when the recurring food shortages and massive food imports in sub-Sahara Africa will either abate, subside, or end altogether. And for that, African countries constantly face food shortages now despite all the good and well-intentioned policies of the international community, the African Union, and African countries themselves intended to address rampant food insecurity, eradicate hunger, and bring food security to millions of low-income African families. So, as a consequence of all that, sub-Saharan Africa today is heavily dependent on food imports than at any time in its history. And as a result of that, it is sadly subjecting millions of its populations to the mercy of foreigners, commodity speculators, foreign exchange fluctuations, food aid giving nations, and the geopolitics of global food trade [11]. In actuality, this is the state of Africa’s food security today. And as a matter of fact, when one looks back at the genesis of this episode, one can say without a doubt that this unfortunate situation could have easily been avoided. That is to say, had the African political leadership shown true leadership, heavily invested in agricultural sector and adopted economic nationalist policies, the early food production crisis, and insecurity beginning in the early 1970s would have been dealt with more effectively. Indeed, past African governments could have substantially invested in food production, assisted the small farmers with more aid and subsidies, and created policy resilience that would have saved thousands of African lives and farmers. And this may have possibly transformed and modernized the entire African food production system. In short, had the political leaders displayed true political courage to undertake such policies as stated, and shown true care for their respective populations, the concerns about the potential socioeconomic catastrophe of the rapid population growth in Africa will not have been as alarming and challenging to us as they seem today. To say the least, Africa suffers from food insecurity today and has been suffering from it for so long simply because of the utter failure and lack of vision, political courage, and sound economic policies of the African leaders and economic decision-makers of all political and ideological stripes on the Continent.
In 1990, Africa’s population was 635 million people. And, in 2018, the population of Africa stood at 1.2 billion people (see Figure 1 below). However, except for the oil exporting African countries (see Table 1), sub-Saharan Africa has, on average, grown a meager 1.1% GDP in the last quarter century [15]. Now, considering Africa’s demographic explosion in the last two decades, this underperforming GDP per capita growth is not sustainable for its long-term economic transformation. And clearly it will not help it either to meet the needs of millions of its young people that are reaching working age and expected to enter the labor market [16] in great numbers every year till the year 2030. This somber forecast is in addition to the fact that Africa’s population is projected to double by 2050 (see Figure 2 and New African March 2019 Guest Commentary by Peter Estlin, the Lord Mayor of London). Therefore, these serious challenges and threats are to be factored into any discussion about Africa’s long-term economic transformation. That is to say, every social, political, and economic actor in Africa should seriously ponder upon them and properly address these threats and challenges. As the youngest continent, Africa has tremendous challenges ahead of it. At the same time, it also has great opportunity to unlock its economic potential that will benefit hundreds of millions of its peoples. However, this can only be done if African political leadership and economic decision-makers unselfishly invest into the youth and give it access to quality health and education and skills of the twenty-first century. And assuming that that warning is heeded, a vibrant, healthy, and educated young population will undoubtedly take upon itself to resolve the issues of food insecurity and nutrition deficits, among many other challenges. As a matter of fact, a great number of economic experts and development economists agree with this economic proposition. They claim that quality health and education are the only engines of economic development that will help unleash the African potential, create inclusive prosperity for all, and economically transform the continent. (For further comments on the subject, see New African March 2019 Guest Commentary by Bill and Melinda Gates).
Evolution of Africa’s population 1960–2019 (Source: [12]).
Africa’s population forecast 2020–2050 (Source: [12]).
Furthermore, Africa’s political leadership, youth, and civil society shall all understand that without some sort of family planning, albeit a voluntary one, the rapid unplanned population growth will never make Africa be food and nutrition secure. Therefore, understanding this reality, and taking also into account the cultural and religious sensitivities of several African communities, Africa’s political leadership, and faith-based organizations of all denominations, should not have any problems investing in women, youth, and young girls. That is to say, in doing so, they will be able to properly educate mothers and future mothers and common people about the consequences of food insecurity and nutrition deficits on the future of their well-being and for Africa as a whole. That’s because an uncontrolled rapid population growth, alongside the climate change threats and its effects, will be a formidable challenge for Africa to overcome if African people are not implicated in seeking solutions for their problems and challenges themselves. In our view, not adopting this policy approach will render the search for Africa’s meaningful economic transformation unattainable just as many other unfulfilled African economic dreams (beginning since the years of its political independence in the 1950s, 1960s, and 1970s). The said contemplated family planning could also be managed through community programs, school programs, and after church and mosque services programs. And by devising such social program plans, educating people in major cities and the rural areas to understand what is truly at stake, and encouraging them to participate into the programs, it will be safe to say that Africans will take upon themselves the transformation of their agricultural production and adopt policies that will help them achieve food security on their own. And as such, they will be able to meet their nutrition needs and targets in line with their burgeoning population growths.
Climate change debates pit true believers of climate change against those that oppose it. They also confront those who are skeptical of its existence or outwardly deny it against those who are fervent believers in it. However, the debates about whether climate change exists or not are beyond the intended purpose of this chapter. In it, we base our analysis on the existence of the climate change threats and its effects as an added challenge to Africa’s existing agriculture commodities’ production, food security, and nutrition needs and targets. In fact, as of today, changes in rainfall, soil quality, weather patterns, and precipitations in many regions of Africa have become the drivers for the food challenges and insecurity in all regions of the continent. And as a result of all that, climate change threats, effects, and stress are now the multiplier for the multitude of the daily challenges that Africans face. Furthermore, it is worth recalling that many countries in the world recognize today that climate change impacts on the temperature, precipitation, and droughts on a given community adversely affect the food security of that community. And consequently, many members of the said affected community are forced to leave and migrate to other communities. That is so because adverse or abrupt climate conditions and threats stress an entire community. And more often than not, they push their younger members to mass migrate. In addition, negative effects of the climate change event like floods and droughts destroy the agricultural production capacity and inputs of the impacted community. So, as an example, communities that have experienced events like droughts and floods whether in the Sahel, the Lake Chad Basin, or East African region [17] have all seen themselves abandoning their homes and villages and moving to neighboring communities or urban cities where they have no adequate resources to help themselves cope with their new surroundings and adapt to their new-found challenges. Many members of the said displaced communities become victims of food insecurity themselves. That is because by abandoning their villages and towns and moving to the new ones, they compete for scarce resources such as water and other daily living amenities in order to survive. Moreover, their sheer presence in their new hometowns or cities swells the pockets of the already established urban poor and makes life more miserable for themselves and everyone else. In short, climate change impacts and its effects have become existential threats to vulnerable communities. And one of the visible effects of climate change today is that climate change impacts turn members of the climate-impacted communities into climate refugees within their new adopted communities.
According to the Fund for Peace, in 2017, the three most fragile states in the world were in Africa. Those states were the Central African Republic (CAR), South Sudan, and Somalia [18]. And each one of them has now become fragile because of the protracted crises that have kept it unstable since the 1960s. In the case of the Central African Republic, the years of the trouble started in the 1960s. In the case of Somalia, the disintegration of its state apparatus and the advent of its successive social, political, and economic challenges came after the fall of the regime of Siad Barre in 1991. In the case of South Sudan, the country has been in political turmoil, standoff, low-intensity warfare since it gained its independence from the Republic of the Sudan in 2011. However, it is worth noting that those three cited-above countries are not the only fragile countries in Africa. There are many other African countries that are also fragile and politically unstable because of the protracted conflicts and never-ending political crises. This is in addition to other crippling challenges such as governance deficiencies, corruption, decades-long underperforming economies, weak institutions, flagrant human rights violations, and living resources scarcity that have kept them from creating an inclusive and shared prosperity for millions of their citizens.4 Indeed, food insecurity and nutritional deficits and the lack of quality health and education are the direct results of the said never-ending challenges that Africa as a whole confronts ever since it gained its political independence from the former colonial powers.
In effect, the persistent lack of peace and security in many sub-Saharan African countries today, coupled with the never-ending political instabilities and crises, is mainly the underlying reasons why African countries seem incapable of tackling and overcoming existential challenges and threats such as food shortages and insecurity and widespread malnutrition on their own. As a case in point, since 2010, a number of civil wars and political crises have broken out in several African countries from Algeria all the way to Kenya. In addition, newer political instabilities and short-lived civil wars have also occurred or unfolded in places like the Lake Chad Basin, Nigeria (Boko Haram), Libya (the bloody ousting of Muammar Kaddafi and the ensuing civil war), Egypt, Tunisia, the Central African Republic (CAR), Kenya, Cameroon, Mali, Burkina Faso, Burundi, South Sudan, Algeria, and Sudan as of late [20]. Moreover, countries such the Democratic Republic of the Congo (DRC), Sudan, and Somalia where decades-long conflicts have weakened and rendered their respective governments inept and unable to assume the administration of their territorial security and come up with sound national economic management policies, transnational threats such as terrorism, mass migration, pandemics such as Ebola and HIV/AIDS, and maritime piracy consume and divert their meager state resources away. Because of all that, their depleted resources are never sufficient to help them successfully fight institutional corruptions, rein into drug trafficking, curb hunger and other social woes, and effectively run their day-to-day administrative affairs. And as a result of the said overwhelming challenges, food insecurity and nutrition challenges currently affect and threaten the lives of millions of South Sudanese, Central Africans, Somali, Nigerians, and million more Africans today. For further illustration of how many African countries are afflicted and overwhelmed by conflicts and protracted crises, and why food security challenges have become existential threats not just to one or two countries in Africa, see Cases of countries affected by food insecurity and acute malnutrition stemming from protracted conflicts, crises, and political unrests and Table 2.
African countries in protracted crises, conflicts, and fragile situations (Source: Data extracted and compiled from [21]).
Nigeria. This country has been grappling with severe security threats from Boko Haram and ISIS West Africa (ISIS-WA). Consequently, these threats have caused massive internal displacement of the population in the northeast region of the country and made thousands of Nigerians domestic refugees. In addition to the displaced Nigerian citizens, thousands more refugees from Niger, Cameroon, Chad, and the Central African Republic have flocked into the region, and consequently swelled the overrun refugee camps and made matters worse for everyone involved in the camps. As a result, they all have become victims of food and nutrition insecurity.
South Sudan. Due to the clashes between the South Sudanese Government and armed opposition groups, millions of South Sudanese have become the largest displaced population in their own country and been made refugees in the neighboring countries. As a consequence, this situation has created a severe case of food insecurity and malnutrition challenges in South Sudan today.
Somalia. This country is another case in Africa where protracted conflicts since 1991 have made it impossible for the Somali population at large to escape from poverty, misery, and the never-ending threats and real cases of food insecurity and chronic malnutrition that have for years affected both the youth and general Somali population.
The Central African Republic. This country is the latest case of food insecurity and widespread malnutrition in Africa. This has been the case since the short-lived Civil War of 2013 and the ensuing political unrest, rebellion, and ongoing sectarian aggressions between the Christian and Muslim communities.
The international community heretofore understood as international institutions; private sector; multinational and transnational corporations (MNCs and TNCs); civil society; private foundations such as the Bill & Melinda Gates Foundation, the Clinton Foundation, and NGOs; leading nations such as the United States, China, India, Russia, and Brazil; the Global South; the European Union (EU); and celebrities like George Clooney, Angelina Jolie, Madonna, Bono, and many others are all stakeholders in food security and hunger debates. However, the United Nations (UN) system has thus far been the leading multilateral institutional voice that addresses and shapes the policy debates and proposes policy prescriptions for the food insecurity and malnutrition challenges that Africa and other regions of the world face.
Within the United Nations system, however, the Food and Agriculture Organization (FAO) which was established as an intergovernmental body is the organization mandated to address the agricultural issues such as food security, nutrition, and malnutrition challenges of its member countries. And as an intergovernmental body, the FAO was formed to promote the “common welfare by furthering separate and collective action for the purpose of raising levels of nutrition and standards of living of the peoples under their respective jurisdictions; securing improvements in the efficiency of the production and distribution of all food and agricultural products; bettering the conditions of rural populations; and thus contributing towards an expanding world economy and ensuring humanity’s freedom from hunger [22].”
Though the FAO has had the mandate to tackle agricultural issues and concerns of its member countries, from its inception, the governments of its member countries were primarily the major actors that formulated and addressed the issues of agriculture within the United Nations’ system. However, since the end of the Cold War, other actors and stakeholders such as the NGOs, CSOs, and a multitude of transnational corporations have also become relevant actors in policy formulations addressing hunger, food issues, and nutrition security governance in Africa. This has especially been so since the establishment of the MDGs covering the year 2000–2015 and the SDGs in place from 2015 to 2030. Nevertheless, this proliferation of stakeholders and actors in food security governance that is now being shared among the UN agencies and the private sector, civil society, NGOs, and the concerned governments has led to an increase in collaboration and partnerships among all the stakeholders that address and formulate policies dealing with the food and nutrition challenges in Africa today. As an example, transnational corporations such as Unilever have now jumped into global threats issues such as world hunger and food security and malnutrition challenges. This is becoming common in corporate governance because leading global corporations have now realized that those aforementioned issues are global threats in nature and no longer local per se. And therefore, they affect everyone and every country in this age of economic, political, technological, and cultural globalization [23]. Furthermore, corporations such as Unilever and many others like it have also understood that addressing those issues as a company or private sector is actually adhering to social corporate responsibility which is increasingly aligned with the interests of a business in this globalized and interdependent world. In fact, this new social-business approach has become the new modus operandi of socially responsible companies everywhere in the world today. In other words, it’s good business to be a global corporate citizen. In effect, big corporations and brand-name companies now understand that consumers want them to also be social citizens while pursuing their economic and business profits and interests [24]. And as a response to all these new developments, in 2013, the FAO published its new strategic framework with a new focus on “governance, creation of enabling environments, and policy support in member countries is the direct outcome of its adaptation and repositioning process.” This new framework was conceived to officially help the FAO collaborate and share policy spaces with other actors and stakeholders in food and nutrition security governance in Africa [25] and anywhere else for that matter.
Africa’s responses to the food security challenges can at best be summarized as ineffective and inefficient thus far, to say the least. However, since the advent of the new millennium and the food crisis of 2007–2008, there has been a somewhat sincere and renewed commitment by the African leaders, the African Union, the Regional Economic Communities, the national governments, civil society, private sector, and all the stakeholders in Africa in support of food security. This new-found engagement in food security challenges is aimed at supporting agricultural production, replacing the prevalence of undernourishment, eradicating hunger, achieving food security, and meeting nutrition needs and targets. This has been so since the 2008 food price hikes and the subsequent social unrest and disturbances that took place in several African capitals and shook the sitting governments of that time. As a result of those vivid developments, the national security implications of food and nutrition insecurity were in plain view for all to see. In addition, the increased awareness of climate change threats and the rising awareness of the unforeseeable consequences of the rapid population growth on the food production system and on the stability of the state made African leaders take note and entice them to initiate various national policies to support food and nutrition security. Soon thereafter, as a result of those political events, several respective African governments devised new policy strategies in line with their national economic policies in support to food production, transformation, and security. For example, countries like Ghana, Nigeria, and Kenya partner more now with the private sector and the civil society in administering and managing their food systems. They basically have shifted their schemes towards private-public partnerships and involved wider private sector(s) in their food production and transformation policies. In contrast, countries like Ethiopia, South Africa, Angola, and Mali have integrated more of their food policy programs in recent years as well. That is, they have aligned them with their national economic strategies to support their food production, combat their food shortages, and replace their prevalent malnutrition. Nevertheless, what remains to be accomplished to date is the transformation of the said renewed political commitments into concrete policy actions such as (1) a visible and sustainable high-level leadership and effective governance, (2) an increase in public-private partnerships (PPPs) and shared co-leadership in fighting against hunger and food insecurity, (3) a supportive and enabling environment by the sitting governments and their decision-makers, and (4) a comprehensive and clear policy approach with all stakeholders involved in support of food production and security. Furthermore, at the continental and regional levels, it is worth highlighting also that the leading voices in formulating policies to combat food insecurity and curb the nutrition challenges in recent decades have been the African Union Commission (AUC), the NEPAD, and the Regional Economic Communities (RECs) such as ECOWAS in West Africa and ECCAS in Central Africa.
The current state of food security and widespread malnutrition in Africa is not as ideal as Africans would like it to be. That is to say, as of today, a good number of African countries are food deficit and insecure. This has been so because food insecurity and widespread malnutrition as stated in this chapter are a multidimensional problem. Challenges that are directly tied to healthcare, misdirected policies and politics, trade and economic interests, weak institutions, failed leadership, and many other variables make it hard and difficult for many African countries to achieve food security. In addition to the internal causes previously discussed as of why a good number of sub-Saharan African countries are not food secure, the chapter also highlighted that there are also external reasons as for why sub-Saharan African countries have been struggling to secure foods for their respective populations and meet their nutrition needs and targets. The chief among those external reasons as discussed and analyzed were economic policy prescriptions that the World Bank and the IMF prescribed for Africa in the 1970s, 1980s, and the latter part of the 1990s. The said policies were devised to help Africa align its economic development policies and strategies with the market-based liberal principles and practices. And as previously explained, the economic conditions of those countries later showed that those policy prescriptions did not provide the intended and expected economic results. Instead, they worsened the food insecurity in Africa. That’s because by advising and encouraging African governments to cut their aid, subsidies, and assistance to their farmers in the name of the market-based principles, food insecurity in sub-Saharan Africa worsened dramatically. Moreover, the chapter also acknowledged that, save the commodities and natural resources exporting African countries, the economic growth of the majority of African countries has not performed as expected either. That is, the GDP growth rates of many sub-Saharan African countries have not kept pace with their rapid respective population growths, especially the rapid urban population growth that many African countries have experienced in recent years. In addition to the mentioned economic policy challenges, new challenges such as climate change and its effects and the internal displacements and migrations pushed many sub-Saharan African countries to depend more on food imports and foreign aid. Consequently, in actuality, many of them are unable to feed their populations today, and food insecurity and malnutrition have become the daily staple of millions of their citizens. Last but not least, the food price hikes of 2008 and their direct political consequences thereof, namely, riots and protests in many African cities, also exposed in plain view the economic policy failures of the African countries to the whole world to see. The rioting and protests showed how inept and incompetent many African leaders had for years been in failing to provide food security to their low-income and respective vulnerable citizens. Also, one of the visible consequences of the failure of African leaders in food security management has thus far been the continuous rise of import food bills in Africa year after year [26, 27, 28, 29, 30, 31, 32, 33, 34], while agriculture dependence has remained high. In sum, the combined reasons as analyzed above are the real reasons why sub-Saharan African countries have for years seemed unable to eradicate hunger, achieve food security, and meet nutrition targets and needs for their people(s). In essence, this is fundamentally why African countries struggled to meet the MDGs targets (2000–2015) despite the assistance and resources granted to them by the international community. With that in mind, if recent history is any indication, sub-Saharan African countries are going to struggle again in order to meet a few targets of the SDGs (2015–2030). In summary, hopefully African leaders will prove their skeptics and all of us wrong this time around.
The diagnostics of Africa’s food security and malnutrition challenges has been thoroughly examined in this chapter. The international community, the African Union and respective African governments and anyone else interested in the issues of food insecurity, climate change threats, and protracted conflicts and wars in Africa have all launched policies against food insecurity in Africa. However, in order for Africa as a whole to achieve food security and lower its dependence on food imports and aid, African political leaders and economic decision-makers will have to surmount in true sense each one of the challenges mentioned in this chapter. For as those challenges are extensively analyzed in this chapter, they have been shown to be the real culprit of Africa’s never ending socioeconomic and political problems. For decades now, they have been the challenges that have crippled Africa and hijacked the well-being and welfare of its citizens. Below are the specific policy proposals that if implemented could contribute to help overcome the challenges of food insecurity and nutrition deficits and many other challenges that have kept Africa for years from meaningful economic transformations beneficial for all its citizens.
African political leadership and economic decision-makers should strive to formulate economic development strategies that are inclusive and people-centered rather than elites and upper middle-class cosmopolitan-driven. That is to say, Africa needs inclusive shared prosperity and constructive policies focused on Africa’s youth and women and solely addressed against the challenges of a population set to double by the year 2050. Employment and job creation policies ought to also be the top priority beyond anything else for the African political leadership. Those are the real challenges that Africa will be facing in the next coming decades.
African political leadership and economic decision-makers should make agriculture a strategic sector and provide African farmers with all kinds of assistance and aid regardless of how unpopular they may appear to the international community and economic experts, and how contrary they may be when evaluated against the market-based principles and policies. In addition, credit and insurance schemes for farmers should also be part of any economic development policy and strategy in any sub-Saharan African country if food security were to ever be achieved. Instituting smart credit and insurance schemes for farmers will inevitably help create robust financial resilience that will protect them from market uncertainty and shocks and keep them focused on food production. Furthermore, civil society organizations, producer organizations, and wider private sector alike should also be allowed to participate in and be part of any policy scheme devised to support food production, combat food insecurity, and curb nutrition deficits.
African political leadership and economic decision-makers should institute and establish social protection programs or food safety net in the likes of cash transfer programs whose objectives should solely be to promote food security and nutrition and provide quality healthcare and education for the youth and women in particular whether in urban centers or in the rural areas. The programs should also serve against food price shocks for low-income citizens that are vulnerable to the market prices’ volatility. Distribution programs and food banks in every neighborhood, town, and city across sub-Saharan Africa should also be established and aggressively promoted while implicating Africans of higher economic and financial means in the programs. The unscathed and seemingly unconcerned wealthy African families should also be invited to co-own the schemes and programs since they are resource-blessed and better off than the majority of their fellow citizens. That is to say, whatever incentive in the likes of tax break or any other financial schemes that may be attractive to them should be on the table for them to consider. Simply put, well-to-do Africans should be reminded of the famous African solidarity and the responsibility that comes with it in assisting their less-blessed brethren.
African political leadership and economic decision-makers should make all kinds of efforts to increase investment in food production and processing and physical transportation infrastructure that will connect rural areas with the growing urban centers where food demands are concentrated. Modern food storage facilities should also be built around major cities and link them to the four geographical corners of the back country. And this can be achieved only if food transportation networks within the country and across the immediate subregions are modernized and resourced.
African political leadership and economic decision-makers should understand once for all that without a sustained political stability and zero tolerance of any sort of institutional or personal (family-induced) corruption, agricultural production and food relief efforts that are badly needed to combat hunger, decisively tackle food insecurity, and achieve the nutrition needs and targets in Africa will never be possible. Peace therefore should be at the center of any national policy and be made the highest priority if Africa does not want to forever be dependent on the good will of foreigners, continuously import foods, and forever beg for development aid and largesse.
JEL Code: N57, Q1, Q5, F63
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