International Journal of Current Research and Review
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IJCRR - 13(14), July, 2021

Pages: 177-183

Date of Publication: 20-Jul-2021


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Human Papilloma Virus (HPV) - A Threat to Women Worldwide: Emerging Solutions for Cervical Cancer

Author: Nichila MP, Grace VMB, Wilson DD

Category: Healthcare

Abstract:Introduction: Human Papilloma Virus (HPV) is a papillomavirus that infects the skin and mucous membranes of humans. It impacts the health of women far more than it impacts men. Approximately 200 HPV types have been identified so far. Some HPV sub-types cause warts (verrucae) and certain others cause cancers including cervical cancer, while others have no symptoms. HPV is the most common sexually transmitted virus infecting human and presents as exophytic verrucous white or pigmented lesions with symptoms of bleeding and pain. The HPV infection and thereby cervical cancer incidence are found to be higher in underdeveloped countries. Aim and Objective: This review aims at summarising the new advancements in the solutions for cervical cancer especially, the HPV targeted therapeutic vaccine developments and prospects. Conclusion: The primary reason noted is the lack of access to screening and awareness about risk factors. However, the applicability of these screening in India is questionable. Furthermore, the women (especially Indians) psychologically don't like to have Pap smear when they don't have any abnormal symptoms. Moreover, the Pap smear test is not so efficient to screen before the onset of cervical lesions. More research is needed in screening methods so that best practices for prevention and management can be developed and implemented. Even though there are Food and Drug Administration (FDA) approved HPV vaccines like Gardasil, Gardasil 9, Cervarix, which prevent infection against various high-risk HPV types, HPV associated diseases remain a significant public health problem since the HPV vaccines do not treat the already infected individuals

Keywords: Cryo microscopy, Prospects, Human papillomavirus, HPV therapeutic, Vaccines, Phytochemicals, Progress in therapy

Full Text:

INTRODUCTION

Human papillomavirus (HPV) infections cause cervical, vulvar, vaginal, penile, anal, and a few head and neck (oropharyngeal) cancers. HPV is considered the major cause of the occurrence of various types of cancer and skin warts.1  The International Agency for Research on Cancer has found that the cancer sites of the cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and tonsil, have a strong causal relationship with HPV.2 HPV is transmitted from skin and mucous membrane of an infected individual to a healthy one through direct sexual contact.3 According to NIH, Human Papilloma Viruses are considered to spread through direct sexual contact. HPV is a non-enveloped, epitheliotropic, double-stranded circular DNA virus, whose gene expression and the life cycle is tightly controlled by epithelial cell differentiation.4The sexually transmitted HPV types are categorised into low risk and high-risk HPV’s based on their oncogenic potential. The low-risk HPV type causes genital warts and is considered non-cancerous lesions. The high-risk HPV types are potential tumour causing agents. HPV can be classified into two main phylogenetic genera namely α-HPV and β-HPV, which corresponds to the mucosal and cutaneous infection respectively.5 The CDC statistics revealed the occurrence of about 39,800 HPV-associated cancers in the United States each year from 2009 to 2013.6 They have highlighted that half of the population is affected by HPV and the recent research has focused on formulating therapeutic drugs, which produce cell-mediated immunity and strong therapeutic effects against established HPV infections and lesions.7

In 2017, the WHO fact sheet revealed that the HPV infection does not show symptoms in most cases, and cervical cancer symptoms tend to appear only at an advanced stage. Hence, regular screening for HPV is important and it highlighted that 90% death by cervical cancer is in middle-income countries.8 Mortality due to cervical cancer is reduced in women who undergo regular pap screening test followed by diagnostic procedures and treatment. It has also been found that screening with Pap test and HPV DNA for every five years in women 30 years and older, is more sensitive in identifying the cervical abnormalities at an early stage and these two tests reduce the incidence of cervical cancer.9 The irony is that there is no HPV specific treatment even if it is identified upon screening to prevent the development risk of cervical cancer which is an alarming situation for women worldwide. The existing HPV managements are vaccination for only very few types and non-specific immune-stimulation regimen against HPV infection. Like the HIV, evolution into new sub-types of HPV is the real challenge of HPV vaccination as well as immunotherapy. Hence, understanding the mechanism of action of HPV will help in formulating better anti-viral therapeutic agents against HPV. Advancement in 3D microscopic view of HPV using a new imaging technique called cryo-EM or cryo microscopy has helped researchers to get a detailed view of HPV structure, the antigen-antibody binding, the epitope region, and the transformational changes that occur when the HPV virus binds to the cell. It was, therefore, suggested to have improved imaging to better research approaches in future.10 This review article highlights the HPV infection as a real threat for women and the various advancements in HPV research to solve the present challenges and their impact on cervical cancer management.

EPIDEMIOLOGY OF CERVICAL CANCER

The leading genital cancer among women worldwide is cervical cancer and millions of new cases reported every year. An account of 239,000 deaths has been reported in 2015 and most of them are with squamous cell carcinoma. It differs in the geographic region. Among 100,000 women, 34.8 new cases and 22.5 deaths are reported in sub-Saharan Africa and 4.4 new cases and 1.9 deaths are reported in Western Asia. The cervical cancer rate is very lower in Northern America. The cervical cancer rate is very high in many countries of Central Asia compared to Europe. In Central Asian Countries, 25,700 cervical cancer cases were reported and 12,700 died of it. The mortality rate in Kyrgyzstan is 11.2 per 100,000 and in Tajikistan 4.9 per 100,000. Increasing morbidity, such as pain, bleeding, and kidney failure are the risk factors of cervical cancer and in poor countries; it is difficult to treat cervical cancer.11It was reported that 57,000 new cases and 311,000 deaths have occurred in 2018, and the highest cases reported in Eswatini at 6.5%. The global cervical burden can be contributed by India and China, 106,000 cases in China with deaths of 48,000 and 97,000 cases with 60,000 deaths in India.12 The WHO made a draft global strategy to be achieved within 2030 by focusing on three main factors as; prevention (90% of girls need to be vaccinated for HPV), screening (70% coverage for cancer and 90% coverage for pre-cancerous cervical lesions) and treatment at the early stage of cancer (Managing 90% of invasive cancer).13

THERAPY FOR CERVICAL CANCER

The promising results achieved in primary treatments of cervical cancer include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. The cisplatin plus Paclitaxel was found to show less toxicity than cisplatin plus fluorouracil,14 which implies that the plant-derived drug Paclitaxel is a good option for treating cervical cancer with reduced toxic effects. Intra-cavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies.15 Treatments other than the primary surgical techniques, which need advanced training and equipment, include carbon dioxide laser ablation, Cavitron Ultrasonic Surgical Aspiration (CUSA), and Mohs surgery.16 Even though various advancements are found in the treatment process of cervical cancer, the recurrence rate is very high due to a specific set of complications. The present treatment methods are only killing the cancer cells and not eliminating the transforming HPV infection. Hence, future research should aim at finding cost-effective HPV targeted techniques to treat the HPV infection as well as to prevent the recurrence of such infections after treatment.

HPV SCREENING STATUS

Women cervical cancer is the most common and globally positioned the fourth as per the IARC report 2019. To prevent it, the Director-General of WHO made a global call to follow strategies of preventing HPV by improving vaccination, treatment and screening at the early stage. It is predicted that, within the next 65 years, about 35-40 million cancer cases will be reported. Two HPV assays such as; Gene Xpertand care HPV have been prequalified by WHO for the screening of HPV to detect the risk of cervical cancer development at the earliest stage. For LMICs, both assays are used, but their price, management and sensitivity varied. The important tool required for effective screening is traceability, community education, provider training, operational management and quality control. To protect women from developing cervical cancer, it was highlighted that the screening for HPV is very important.17They have described the HPV based cervical cancer screening program: main interventions, ideal timelines and main bottlenecks.

There are over 150 serotypes of HPV, out of which only the high-risk serotypes are identified as potential cancer-causing agents.1 Regular screening of HPV is important for both the vaccinated and the non-vaccinated population because, vaccines will not protect the individuals who are already infected with HPV and also, the vaccine doesn’t provide protection against other oncogenic HPV types. Hence, there is a need for screening at regular intervals for both men and women. There are three common types of screening techniques: Pap test, HPV DNA test, and visual inspection with acetic acid.18The use of the Pap test is not promoted nowadays because of its complexity and delay in managing the patients. Furthermore, HPV testing is easier to identify the positive cases. It has been found that HPV DNA and HPV RNA test detects precancerous lesions at an early stage. The US FDA has approved the HPV DNA test alone in 2014, as primary screening for cervical cancer in women, aged 25 and older.

HPV screening by Pap test and HPV DNA test (co-testing) are reported to reduce cervical abnormalities.19 For stratifying CIN-3 risk, Pap cytology and HPV co-testing were considered valuable and the results taken in three-year interval revealed that the risk of CIN 3 was low in the individuals with negative pap test and HPV co-testing.20 However, it has been found that co-testing is associated with more false positives9, which may be due to genotypic variations of HPV. Various advanced screening techniques include human papillomavirus [HPV]-based screening with partial genotyping. For women testing positive for HPV16/18, colposcopy is carried out and Liquid-based cytology [LBC] for other oncogenic HPV types. For unscreened and under-screened women, HPV testing on self-collected cervicovaginal samples is done. Self-collection is restricted to the age group of women 30-74, who have never been screened for HPV.21 Other advanced HPV screening tests approved by FDA for specific HPV types include; i) Cobas HPV Test specific for HPV 18/16 (approved in 2011) 22, ii) Hybrid Capture 2 test which detects 13 types of "high-risk" HPV types (in 2003), iii) Aptima assay test to detect RNA synthesised when the HPV starts creating cervical cancer (in 2011)23 are highly sensitive and expensive. Hence, there is a need for the development of cost-effective screening techniques for all HPV types with high specificity and sensitivity to prevent false positive detection.

HPV TREATMENTS

There are various types of HPV infection; low-risk HPV infection generally causes warts in various parts of the body including genital region, foot corn, acne and squamous intraepithelial lesions (SIL). Treatment for these kinds of effects by HPV infection includes eliminating the visible lesions and boosting the host immune system to control the viral replication. Treatment of HPV is based on various factors like size, morphology, number and site of lesion, cost of treatment, adverse reaction, and previous treatment. No particular mode of treatment for all the type of HPV infection has been demonstrated.24 Based on the grade level, various treatment methods like cryotherapy, a loop electrosurgical excision procedure (LEEP) diagnostic excisional procedure (cone biopsy) are given.25 Pharmacological therapy for the treatment of HPV is classified into two categories namely, immune response modifiers and cytotoxic agents. These drugs are given cutaneously against anogenital warts or condylomata acuminate.26The main challenge in HPV treatment is the lack of in vitro HPV culture model to study the efficiency of treatments. Hence, no specific drug has been established yet. As a result, cervical cancer causes more than one quarter of a million deaths every year in underdeveloped and developing countries. In SIL patients, if the high-risk type HPV persists, it will be turned into neoplasia and invasive cervical cancer.

HPV VACCINATION AS A MODE OF TREATMENT

The HPV vaccination is given as either a prophylactic vaccine or therapeutic vaccine. The prophylactic HPV vaccination using HPV antigens can reduce the prevalence of HPV infection and thereby, reduce the risk or incidence of cervical cancer development. The existing prophylactic vaccines induce immunity against the L1 protein of HPV particle (Immunization with VLP), but they don’t give therapeutic effect on existing infection and established cervical lesions.27,28,29 In contrast, the therapeutic vaccines are targeted at inducing the cytotoxic cells like T-cells to eliminate the HPV infected cells. The present prevalence and persistence of HPV infection globally indicate that most of the underdeveloped areas have less or no exposure to the prophylactic vaccines and these are the places, which are infected epidemically by the HPV. HPV awareness and vaccination do not seem to reduce the HPV infection rate since, half of the population is already infected and may develop cervical cancer if they are not subjected to affordable screening and treatment procedures.30Hence, the therapeutic vaccination needs to be strengthened to act on established HPV oncogenic types. In 2016, a survey carried out in 1200 Korean representatives revealed that proper knowledge and awareness of HPV infection and vaccination programmes increase the willingness of the individuals to take up the HPV vaccine.31 The VLP vaccines do not protect all oncogenic types. Screening of cancer is very important in the reduction of cancer rate and is very less in many countries. The manufacturing cost of the VLP vaccines is very high and not very effective. For improving the HPV vaccination GAVI is an important tool.32,33

  1. Preventing HPV Infection by Prophylactic Vaccines

         To reduce HPV infection, prophylactic vaccines play an important role as it is eliciting a humoral immune response against HPV infection. There are two well established prophylactic HPV vaccines available to act against the L1 capsid proteins. The first developed quadrivalent vaccine was Gardasil®, which has been available since 2006; it provides protection against HPV 6, 11, 16, and 18 for at least 8 years. The second was the Cervarix®, which protects against two serotypes 16 and 18 for more than 9 years.33 Effectiveness of this HPV vaccine in providing prevention and long-term protection against genital warts was higher in individuals with three doses than one dose since the risk of genital warts rose with age.34 The effectiveness and immunogenicity study of a new version Gardasil 9® was found to prevent effectively the 9 HPV serotypes such as HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. This vaccine is cost-effective and approved for clinical use with a promise to prevent for at least 30 years 35, 36,37. However, a cross-reactivity challenge exists for all these prophylactic vaccines. The most adverse effect related to the injection site was mild or moderate in intensity due to the high amount of HPV virus particle and AAHS adjuvants. It has been found that the 9vHPV vaccine increased the overall prevention of cervical cancer from 70% to 90% approximately. Regular screening tests should be done to check HPV infection.38In over 100 countries prophylactic HPV vaccines that include Cervarix (2vHPV vaccine), Gardasil (4vHPV vaccine) and Gardasil 9 (9vHPV vaccine) are licensed since 2006. WHO confirms the efficacy, safety, and the duration of the prophylactic HPV vaccine. However, the HPV vaccines were terminated by the Japanese government due to the local pain syndrome. So the vaccination rate has decreased to 3.9% in Japan. The recent advancements are the development of neutralizing antibodies along with inactivated pathogens to induce the immunization of HPV vaccine with adjuvants. Immunoglobulin G serum response was promoted by 2vHPV vaccines and required for the production of T helper cell 1 biased cell response. 4vHPV vaccine also was found to produce T helper cell 2 biased cell responses.29

          In addition to this L1 based vaccine, later the L2 based vaccines using a conserved 11-200 or 20-38 amino acid chain of N-terminal region have been developed.30 L2 based vaccines provide cross-protection against different types of HPV while the L1 immune response is highly specific. For providing broad cross-neutralization activity, the RG1 epitope within the region is pivotal. Because of the simple format and protection against a wide range of HPVs, the L2s based vaccines are highly acceptable. Many HPV L1 VLP, and HPV L2 based vaccines are produced now usingS. cerevisia, Escherichia coli (E.coli),  methylotrophic yeast species like Hansenulapolymorpha (H.polymorpha) and Pichiapastpris (P.pastoris) and undergoing preclinical or clinical studies.31 However, the immunogenicity is less for L2 based vaccines as a limiting factor for the success. A review article of 1998 has shown the milestone of prophylactic HPV vaccine development starting from the trial of monovalent HPV16 vaccine to the recommendation of an FDA approved vaccine 9vHPV in 2014 with second dosing in 2016 and the recent licencing of a novel E.coli produced bivalent HPV vaccine in China in 2020.39 However, the prophylactic vaccine coverage of all types of high-risk HPV, phylogenetic evolution, lack of awareness and vaccine cost are the challenges for developing countries.

  1. Elimination of HPV by Therapeutic Vaccines

There is a need for the formulation of therapeutic vaccines to treat the already existing HPV infection and the associated diseases. But there is no specific anti-viral drug and the vaccines can induce acquired cellular immune response, which recognizes the infected cells and kills them. Therapeutic vaccines, therefore, aim at inducing a cell-mediated immunity, to kill the target cell. Such vaccines can target all the proteins involved in the entire life cycle of the HPV in the epithelial cells. The L1 and L2 proteins are expressed only in terminal keratinocytes. Hence, the early genes E1, E2, E4, E5, E6, and E7 are ideal targets of therapeutic vaccine development. This can be achieved with HPV peptides, proteins, DNA and also by developing HPV immune-stimulated DC in vitro.22 Most of these vaccines target the oncoproteins E6 and E7, which are responsible for the malignant progression of HPV infection. There are different forms of therapeutic vaccines that are used in the clinical trial phase, and these include bacteria-based vaccines (Lm –LLO-E7),23 Viral vector-based (TA-HPV),24 Nucleotide based (pNGVL4a-CRT/E7 –DNA),25 whole cell-based (1, dendritic cell-based 2, tumour cell-based), peptide-based (HPV 16-SLP),26 protein(GTL001).27 The main strategies of HPV therapeutic vaccines are generating specific effectors T- Cell against the expression of oncogene E6 and E7. Recently, many clinical trials for therapeutic vaccines have been conducted with optimization to improve the efficacy. Shortly, the development of these drugs may pave the way for the eradication of HPV infection and associated diseases including deadly cancer.

CHALLENGES IN HPV VACCINATION

         The most important issue is the lack of knowledge about HPV and its vaccines, so it should be addressed. Delivery of the vaccines should be affordable, available and acceptable. China approved many HPV vaccines but the availability is very less mainly in lower resources regions. In France, the delivery of HPV vaccines is below 20%. The major issue is that the women or girls are not taking the vaccine even it is given free of cost. HPV based self-sampling kits are available, which will improve participation as it is acceptable than the clinical sampling.28

     In Nigeria, the facilities are very less for cervical cancer screening and the awareness is also lower. So 97.9% of women are not screened for cervical cancer. Some of the issues include lack of screening service (44.2%), lack of knowledge (40.7%), reduction in decision-making ability (34.2%), cost of screening (30.1%), and the distance of the centre (23.5%). But the HPV related diseases can be compacted by cytology screening. It provides high sensitivity, high throughput, and negative predictive value. HPV worldwide have licensed two safer quadrivalent and bivalent vaccines. But the use of the vaccines is reduced due to the lack of knowledge and high cost. Cervarix and Gardasil vaccines are donated through GAVI INITIATIVE (Global alliance for vaccine and immunization) at lower price mainly to low-income countries. An issue stated by other countries is that those vaccines contain a high amount of aluminium salt which causes damage to the immune system especially in infants and children which leads to chronic illness.49Hence, new safer delivery regimens need to be invented.27-30

        The exact mechanism behind HPV integration with the host cells is not known yet. Understanding the HPV oncoproteins structure and mechanism of their interactions will help in the formulation of better medicines and effective prophylactic vaccines, which will help in the eradication of HPV shortly. The cryo-electron microscopic examination has given a better understanding of the structure of HPV 16 particle capsids and the structural conformational changes which occur when HPV binds to the cell10 and the results help in understanding the HPV uptake mechanism during the early stage of virus infection. This imaging technique will help in understanding the antigen-antibody interactions, thus more specific vaccines which prevent and cure HPV infection can be formulated in the future.31

DISCUSSION

           Based on the reviews summarized and presented at Asia-Oceanic Research Organization in Genital Infection and Neoplasia (AOGIN) 2018, and the 32nd International Papillomavirus Conference (IPVC), the Director-General of the World Health Organization (WHO) announced that cervical cancer can be cured affordably by implementing the draft static plans. Their main goal is to prevent cervical cancer by improving the vaccination among 90% of females globally. The prophylactic vaccination is implemented in high-income countries on large scale, however, the supply of HPV vaccines and the acceptance of the need for vaccination among young adolescent girls is the current challenge in these countries. It was highlighted that clinical validation such as dose efficacy, bridging, safety studies are required for the infant immunization against HPV. For LMIC, vaccinating the young girls at a large coverage (80-100% coverage and 70% screening twice per lifetime) should be prioritized, which can reduce cervical cancer from 16 per 100 000 to less than 4 per 100 000 in between 2020 and 2080.32

        For treating HPV induced lesions, a therapeutic regimen plays a major role. It is possible to eradicate HPV-transformed cells through immune response produced by HPV genes that carry the recombinant vaccinia virus. The E2 of HPV is getting much attention as an effective target for developing therapeutic vaccines as it plays a major role in transmitting the HPV into the new cells in the cervix epithelium. Tumour can be eliminated through MVA E2 vaccines that stimulate the production of antibodies and cytotoxic cells that act directly on the transformed cells. MVA E2 vaccines are promising agents for preventing as well as treating cervical cancer and did not show any side effects when tested in the patient.21

Current Status and Future Prospects of Cervical Cancer Therapy

            In Germany, the cervical cancer prevention analysis was attempted by Wolfsburg Pilot Project for non-hysterectomies women (30-70 years old), where cervical cancer diagnosed in the first screening compared with subsequent round was the primary focus. The women can freely choose HPV test or Pap smear under health insurance companies within a five years gap. The positive women are referred to colposcopy and the next screening should be after five years for negative women.12

          The current therapies for cervical cancer are only cytotoxic which causes injuries to normal cells. Furthermore, since the high-risk type HPV is the inducer of cervical cancer, the recurrence rate is also very high in cervical cancer treatment. Cisplatin, the key drug used for cervical cancer, gives rise to adverse side effects such as nephrotoxicity and neurotoxicity33,34. For pursuing better health, medicinal plants are nature’s gift. Several studies have proven that plants contain bioactive compounds that can act against particular cancer. Allium Wallichil contains phytochemicals like cateroids, flavonoids, terpenoids, Paeoniasuffruticosa has phytochemicals such as polysaccharides (HSS, DASS, HBSS, CASC) and all these can suppress cervical cancer. Phytochemicals identified in Medicagoscutellata are trypsin inhibitor, which can decrease cervical cancer as well as other types of cancers. The bioassay-guided fractionation of these phytochemicals may achieve a better anti-cancer therapy.35 Black raspberries and their compounds are the promising ones for cervical cancer in chemoprevention. Boswellia Srerata can induce apoptosis and kill cancer cells by the hydro alcoholic compound.56 Furthermore cervical cancer treatment will be effective only when the causative HPV is targeted. But so far no drug formulation with anti-viral property is available for cervical cancer therapy. The efficient anti-viral potential of garlic extract containing allicin was shown by Weber and his research group in vitro on HeLa cell line.27

The vaccines and screening programs have been developed in the area of HPV over the last 36 years. But the investigation is still going on for HPV related cancer and HPV infection. The most promising area of research worldwide is immunotherapy, but it has not been approved by FDA. Risk factor screening programs and global implementation of vaccines programs should be followed for the reduction of HPV associated cancer. Screening by HPV-FASTER and vaccination should be compelled to youngsters.28

CONCLUSION

       In future, if research is focused on understanding the mechanism of action of HPV in the host,  it might pave way for formulating better therapeutics. More awareness should be given on the importance of vaccination at an early stage itself. There is a need to work towards formulating a single vaccine with high immunogenicity, specificity, safety and patient acceptance, which can act against all types of HPV. Continuous screening for HPV at regular intervals followed by HPV targeted treatment can reduce the deaths caused due to cervical cancer. Researchers are focussing on natural extracts for the treatment of cancer. Phyto-molecules have high biocompatibility and biodegradability that can increase efficacy in cervical cancer therapy. Research works are currently undergoing for the evaluation of phytochemicals that act against HPV in cervical cancer cells.

Acknowledgement:

The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Conflict of Interest:

            The authors declare that they have no conflict of interest in the writing and publishing of this review article.

Funding for this study:

Nil

Authorship and Responsibilities:

Nichila MP – Data Collection and Writing

Grace VMB – Planning, Design and Writing

Wilson DD - planning, Writing and Editing

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  38. Cutts FT,  Franceschi S, Goldie S,  Castellsague X, Sanjose SD, Garnett G. et al. Human papillomavirus and HPV vaccines: a review.  New Engl J Med.  2015; 372: 711-723.

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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