The Human Papillomavirus and Cervical Cancer - Term Paper Example

THE EFFECT THAT THE HUMAN PAPILLOMAVIRUS MAY HAVE IN THE FUTURE ON CERVICA CANCER By (Student’s name) 1. INTRODUCTION Dating back to the Hippocrates era, it is quite evident that there has been a tremendous shift in medical practice with particular reference to the evolution of evidence-based medicine. Currently, clinical decisions and treatments are no longer based on intuitions or outdated standardized procedures but are rather based on evidence that has been founded on strong evidence that has been obtained through the use of sound scientific methods. This has been informed in part by the fact that globalization and technology has brought with it opportunities and challenges which requires a shift from the traditional way of behavior, thinking and actions. Indeed evidence-based practice must lend credence to the evolution of research; a phenomenon that has formed the basis for acquiring knowledge and information. In the dynamic world that we currently live in, there is an urgent need for not only timely information but also for accurate and reliable information. Therefore, as Besley (2009) puts it the most exciting aspect of research is that it has been able to satisfy the urgent need of this accurate and reliable knowledge by the stakeholders in the medical field. In turn, this knowledge has led to the innovation of procedures and treatments that have made clinical practice safe and efficient. According to Besley (2009), innumerable researches have been carried out over the last decade in the field of medicine ranging from experiments, observational studies as well logical arguments from traditionally accepted postulate with an aim of improving the practice of medical professionals. In essence, research deals with the collection of data and then collating the raw data collected in order to make sense out of it. It is from this collated data that inferences and recommendations are made that influences policy and practice. It is thus worth noting at this point in time that research forms an integral part in any clinical practice. As earlier stated, research findings have been used to develop clinical procedure and treatments that have now made medical practice easy and improved the quality of life. To ensure that these procedures and treatments are kept for posterity and for future reference, several resources for evidence based practice have been developed by different players in the medical field. To begin with we have research articles which contain published results of different studies and these articles include mainly journals of reputable medical institutions. Secondly, we have the clinical practice guidelines that contain standardized procedures that guide health practitioners on how to provide appropriate care to the patients. Normally, clinical practice guidelines are produced by reputable authorities, such as the World Health Organization, and are based on the most current and relevant research. In most cases, research findings can be too long and not able to be published. For such cases, structured abstracts and evidence summaries have been used the best available results (Besley, 2009). Furthermore, other resource for evidence based practice is the systematic reviews and meta-analysis. In systematic reviews, different researches are critically analysed and reviews on the basis of their methodologies, results and relevance. In meta-analysis on the other hand, results from a research are combined together for making inferences. The last resource for evidence based practice is meta-search engines which draws materials from updated online sources (Besley, 2009). Having considered research in general as well as a preview of evidence based practice and the different resources for this practice, it is necessary to also consider other aspects of research. Firstly is reliability. In research, reliability is used to refer to the degree to which a study instrument can yield consistent data after numerous trials have been carried out. This is always influenced by random error which is a deviation from accuracy due to factors that may not have been addressed effectively. In a randomised controlled trial for instance; the results within the intervention and control groups must be consistent throughout for the test to be considered reliable. However, an error may occur if there was a bias in selecting subjects and assigning treatment to them (Hulley et al., 2007). Another important aspect is validity. Hulley et al. (2007) have defined validity as simply the ability of test to distinguish who has and who does not have the disease in question and this is based on the results of the test. In research, results form the basis for making accurate and meaningful inferences and it is from such inferences that the research can be said to be either valid or not. In a randomised controlled trail for instance, the study can be said to be valid if the results clearly identifies occurrence of disease in placebo and absence of disease in the control group and from this the treatment can be said to be efficacious. Moreover, any scientific study relies on empirical evidence that is rooted in object reality and gathered either directly or indirectly through the human senses. This ensures that the research results are grounded on reality and not the beliefs of the researcher. Empirical evidence is thus, in Besley’s perspective, the observations made known by the way of our senses. Lastly, qualitative research is the type of research that yield data in the form of word and not numbers and these words are often grouped. A classical example of this research is observational studies. This is contrary to the quantitative research that yields data which is in discreet numbers. A classical example is experimental studies (Besley, 2009). The rationale behind the two papers under review is to measure the efficacy of Human Papillomavirus (HPV) vaccines and screening in the management of cervical cancer. The first paper fro the British Journal of cancer compares HPV vaccines with screening methods to form a basis for deciding on which procedure to adopt. The second paper from the British Medical Bulletin explores the efficacy of HPV vaccines based on the randomised controlled trail to determine whether vaccines are the answer to cervical cancer management. The rationale for the choice of this topic was informed on my experience working as a practice nurse in primary care. Essentially, primary care brings promotion and prevention, cure and care together in a safe, effective and socially productive way. Importantly, this care incorporates aspects of counseling, patient education and diagnosis of acute and chronic diseases. Primary care thus forms a basis for measuring the effectiveness of vaccines for HPV and screening for cervical cancer. In addition, I have an ardent desire in cytology which is integral in the clinical research of cervical cancer on the basis that it studies cell structures to diagnose disease. Screening for cervical cancer and the development of HPV vaccines has been based on the recognition of the similarities and differences in cells. Basing my topic choice on these two premises formed a foundation for getting more insights in the advances that have been in the prevention, treatment and management of cervical cancer with particular reference to HPV vaccines. 2. APPRAISAL OF EVIDENCE 2.1 Ethical Issues in Research The changing social and scientific context in which research is conducted has elicited new challenges for the researchers, for those who use the results and for the general public. The fact that clinical research has resulted in significant benefits for society cannot be disputed. However, clinical research has had a share of its setbacks that continue to pose profound ethical questions. Critical to this is the use of human subjects in research. The main concern has been how to treat human subjects in the research without causing detrimental effects to them (Gallin and Ognibene, 2002). According to Gallin and Ognibene (2002), ethical issues in research have been classified into three categories i.e. those concerning the researcher, the participants and the research process. To begin with, the research has to maintain high standards of integrity while carrying out the research meaning that research should not be done for personal gains. Secondly, the research must not pass another researchers ideas as his own original work (plagiarism) of fake another researcher’s work fraud). Lastly the researcher must be trustworthy and not misuse his privileges. With regard to study subjects, their confidentiality and privacy must first and foremost be observed at all times. Secondly, an informed consent must be sought from the study subjects and participation in the research must be voluntary. Thirdly, their autonomy must be secured and this can be best done by assigning numbers or pseudo names and not their real names. Importantly, vulnerable populations such as children and the disabled must not be used unless prior consent is obtained from their guardians. Lastly, the researcher must protect study subjects from intentional physical and/or psychological harm (Gallin and Ognibene, 2002). Concerning the research process, the researcher should not ignore pertinent issues in research but should be honest and free to discuss any findings. In experimenting designs like RCTs, the treatment given to the intervention group and has proven efficacy must be also given to the control group after the study as it will help reduce the feeling of unfairness among the controls. Lastly, the researcher has the responsibility of choosing data collection tools that are free of anxiety to make the participants feel at ease (Gallin and Ognibene, 2002). Clinically relevant and ethically acceptable endpoints were important issues for the HPV vaccine RCTs. Both virological and clinical endpoints were potential vaccine trial endpoints. High grade intra-epithelial lesions (CIN 2/3 or AIS) are recognized as the immediate precursors of invasive cervical cancer and for vaccine licensure the endpoint of CIN 2/3 or AIS or worse has been accepted widely as the ethically acceptable proxy for vaccine efficacy against cervical cancer. This endpoint can be evaluated among young women but in children or young adolescents, however, CIN as an endpoint is ethically unacceptable since cervical specimens would be required. Bridging studies have therefore been conducted in children and young adolescents by comparing antibody responses in these cohorts with those in the women for whom efficacy has been evaluated using the CIN endpoint (Stanley, 2008). To sum it up, ethical review boards have been set up to review and pass protocols for researches involving human subjects. Therefore, it is the responsibility of the researchers to submit their research proposals to the board so that it can be passed through a scientific peer review to assess its methodologies and implications in order to avoid exploitation of study subjects (Gallin and Ognibene, 2002). 2.2 Research Methods/Design What forms the backbone of any research is the research’s question. This is based on the fact that research questions determine the type of research design to adopt and also forms the basis for formulating research objectives. The rationale for the studies under review was to evaluate the effectiveness of Human Papillomavirus (HPV) vaccine in the prevention of cervical cancer and so the research question was whether the vaccines are likely to help prevent incidences of cervical cancer or not. Having identified the research question, the next step is to choose an appropriate research design that will answer the thus asked question. In essence, in measuring the effectiveness of a vaccine, there will a need to have subjects who will be given the vaccine and those who will not be given so that an evaluation can be made based on the occurrence of a disease after the study. For this purpose the randomised controlled trial will be the appropriate study design to evaluate the effectiveness of the vaccines (Besley, 2009). Besley (2009) argues that randomised controlled trails always involve the selection of subjects randomly and then assigning them again randomly to the intervention group or to the control group (placebo). As easy as it may sound, this process of selecting subjects and assigning them to particular treatment is always prone to bias that affects the study results. The good news is that bias can be minimised by the use of a control group, randomisation and blinding all of which are elements of randomised controlled trials. The control group (placebo) is given an ineffective vaccine while the intervention group is given the treatment and then a comparison is made on how well patients given the treatment perform with how well the patients not given the intervention perform. It is important to ensure that patients in the both groups are similar in all aspects with the only difference being the treatment being tested. Therefore, the researcher has the obligation to check if the aspects that may lead to differences between the groups have been avoided. In order to achieve this, randomisation is employed to ensure that two groups that are similar in all important aspects have been selected by chance. In addition, it is important to blind the subjects to which treatment they receive and if possible the research staff to which treatment they assign. This is crucial in avoiding unnecessary expectations that may influence the results (Besley, 2009). Critical to the research design is the composition of the groups. Besley (2009) insists that the researcher must ensure that the groups are uniform throughout the research and that no changes are made in the course of the study. Moreover, the researcher must also put into consideration the dropout rate, treatment withdrawal and the number of patients lost to follow-up as this will have a bearing on the results obtained. Having considered these aspects, another critical aspect is analysis of the results. In randomised controlled trials, patients/subject must be analysed in the groups in which they were assigned to even if they did not receive the treatment they were assigned to. In practice, odds ratios, risk ratios and the number needed for treatment are methods of analysis that are used to ascertain if an intervention is effective or not. In addition, the confidence interval (C.I) usually tested at 95% level of confidence is used to give the range where the truth must lie given the findings of the study. The measure of probability (b) is also employed in the analysis (Besley, 2009). 2.3 Critical Appraisal Skills Programme (CASP) Article 1: HPV vaccines: are they the answer? (Stanley, 2008). Firstly, the study clearly asked the question which was whether the optimism surrounding HPV vaccine was justified whether the vaccines have a public health benefit. The population studied were: in the quadrivalent vaccine test, women aged 16-24 years with less than 4 sex partners and naïve for ≥1 HPV vaccines genotypes at enrolment and in the bivalent vaccine test, women aged 15-25 years of age with ≤ 6 life time sex partners and DNA negative for the relevant oncogenic HPV type in the vaccine at trial entry Secondly, the studies were randomised controlled trials as they had a control and intervention group and were thus appropriate to measure the effectiveness of the vaccines. The studies are worth continuing as the vaccines protect against only two of the 15 oncogenic genital HPV types and there is a need to develop multi-vaccines. In addition, there is need to generate cheap, thermostable and non-injectible vaccines as well as those immunogenic in immunocompromised individuals. Thirdly, participants were appropriately allocated to intervention and control group. The women in the specified age group who had no evidence of infection with the HPV genotypes in the vaccine at trial entry were three doses of the vaccine or placebo. The studies did not specify how randomisation schedule was generated and how the participants were allocated to study group. The groups were well balanced and no differences were reported that might have explained any outcome(s). Fourth, it is not clear whether the participants, staff and the study personnel were blinded to participants’ study group. In my opinion blinding matters as it checks incidences of prior expectations. Fifth, all the participants were accounted for at the end of the study; 0.1% percent discontinued to adverse consequences and 17 died mostly from motor accidents. The participants were followed and there was no loss-to-follow-up. Quadrivalent vaccine group was followed for 3 years while the bivalent was followed for 14.8 months. Participants were followed up and data collected in the same way as well as reviewed at the same intervals. There is no mention of whether the participants received the same attention from the researchers and health workers. 20, 583 participants were included in the studies and this was enough to minimise the play of chance. Vaccine efficacy was calculated by comparing the incidence in women who received the vaccine and women who received placebo. Results were expressed as a percentage with the corresponding 95% confidence limits. Analysis were conducted usually in the per protocol (PP) or according to protocol groups. Both vaccines are immunogenic and well tolerated. They have been shown in the various randomised controlled trials to be very effective at preventing infection and premalignant disease related to the vaccine HPV genotypes in women who are DNA negative and sero-negative for the vaccine HPV types at base line. The results are very precise and the efficacy of the vaccines has been presented at a higher confidence level and therefore the decision to use the vaccines will be based at the higher interval and will not be the same as that at the lower interval. Since the confidence intervals have been used, there are no p-values. Article 2: HPV and cervical cancer: screening or vaccination? (Bosch et al., 2008). The study question was whether to adopt vaccines or screening techniques or both. The article reviewed contributions from the editors of the British Journal of cancer include references from relevant studies. The included studies were sufficiently valid to answer the question asked. The results from the studies cited were homogeneous. Therefore, given the nature by which the paper has been presented, the capacity to carry out a critical appraisal skills program (CASP) is limited. In addition, most of the studies reviewed are still ongoing and therefore making it hard to ascertain the results. 2.3 Strength of the Evidence Both the bivalent and quadrivalent vaccines have shown very high efficacy against intra-epithelial neoplasia in the RCTs. In the FUTURE I RCT designed to evaluate efficacy of quadrivalent vaccine in preventing HPV6/11/16/18 caused anogenital disease, vaccine efficacy in the per protocol group was 100% i.e. no cases of HPV 6/11/16/18 caused CIN, VIN, VaIN or external genital warts detected in the vaccine over a 3-year period. A combined analysis of RCTs (Phase IIb and Phase III trails) involving 20,583 women efficacy against HPV 16/18 caused CIN 2/3 was 99% (one case in the vaccine group) and 100% for HPV 16/18-related AIS (Stanley, 2008). The bivalent vaccine in the Phase iii RCT has shown 90.4% efficacy against HPV 16.18 CIN2+, two cases in the vaccine group and 21 cases in the placebo. It is unlikely that the two cases in the vaccine group caused the CIN2+lesions. Moreover, in the per protocol group i.e. women who are naïve at entry for HPV 16/18, efficacy against high grade disease is greater than 98%. However, in the intention to treat group i.e. women entering the trail irrespective of baseline HPV status or evidence of HPV-related disease of any grade and for whom endpoint follow-up started 1 day after trial entry, efficacy against 16/18-related CIN2+ or AIS was 44% (Stanley, 2008). In the phase IIb, immunogenicity trial 001/007 of the bivalent vaccine anti-HPV 16 and 18 antibody persisted at levels that observed in natural infection for at least 6 years post immunization. Antibody levels induced by the quadrivalent vaccine persist in most vaccines 5-6 years post-vaccination and the mathematical modeling of kinetics of antibody decay suggests that detectable antibody could persist for 30 years (Stanley, 2008). 3. IMPLICATIONS FOR PRACTICE 3.1 Ethical Issues in Research Findings Application When a study has been completed, two pertinent issues always arise: who owns the data and who should have access to the data and under what conditions should the data be access. Other issues that arise are who the custodian of the data is and how the data can be shared or disseminated. We live in an era where we can be confident that virtually any research data generated that deal with a controversial issue will be reanalyzed by the real or alleged experts who support different positions in their favor. The paramount ethical principle is to safeguard the collected data to curb incidences of misuse and manipulation (Besley, 2009). On this account, Besley (2009) has put forward conditions that must be met before anybody can be allowed to have access to any data especially where human subjects have been involved. First, access of data must be essential only to the achievement of the objective of the research and to this end, the consent of the custodian of the data must be obtained. Second, the data must be protected against exposure to any persons not immediately involved in the research. Lastly, the data must not be used for any new research without prior consent from the custodian and a further ethical review. 3.2 Factors Influencing Barriers to Research Utilization In today’s rapidly changing healthcare environment in which health professionals are often confronted with short staffing, cost reductions and heavy patient loads, the implementation of a change to evidence –based practice can be a daunting process. In essence, individual, team and organization changes are often complex and lengthy process. One important factor influencing barriers to research utilization is the lack of adequate support from the organization. This is demonstrated with the unwillingness of managers to give practitioners adequate time to use research findings and also to carry out research in the first place. Moreover, accessibility of research findings can be excruciatingly slow especially where the custodians are not willing to share the findings and where bureaucracies are involved. Another equally important factor is lack of adequate funds to carry out research which is always a long and deer venture. This is always supported by the underfunding of research institutions or when organizations and government are yet to prioritize research as an intervention tool in healthcare. 3.3 Recommendations for Change From the studies considered by Stanley (2008), HPV vaccines have proved to be efficacious in the prevention of cervical cancer. This is good news to developing countries that carry the burden of cervical cancer given their inadequate screening programs and poor infrastructure. HPV vaccines will therefore have a great impact on the prevention of cervical cancer in the developing world even though this will have several challenges. Bosch et al. (2008) argue that developing countries already have organized systems in place for Expanded Programs on Immunization (EPI) that are effective in child immunization. It is therefore incumbent on stakeholders in the health system to come up with programs that will incorporate HPV vaccines into the EPI programs. This will include specifying the dosage for children as well as making provisions for the adolescents. Ideally, HPV vaccines can be included in the school health programs in areas where primary health care programs for school children are effective. HPV vaccines have shown to be effective in preventing of HPV genotypes 16/18 among the sero-negative individuals (Stanley, 2008). Therefore, new technologies for screening should be put in place that will adopt different protocols such as the check and treat protocol. This will be important in the sense that it will minimize the number of visits to the hospital for screening. Bosch et al. (2008) have suggested the development of simpler screening techniques that will minimize the frequency of screening, coats as well as accessibility by the larger populations. Moreover, Bosch et al. (2008) have noted the high costs involved in the production of HPV vaccines which cannt be attained by poor nations that are in most need of the vaccines. Therefore to counter the cost of HPV vaccines, charitable health organizations have to be convinced to purchase large lots of the vaccines, once they have are licensed for testing and eventually general distribution in low resource areas. In addition, there should be the development of second-class vaccines that could be produced and delivered at lower costs. To ensure that there is still compliance to Pap smears in the wake of vaccines, it may be necessary to mount public sector efforts to emphasize the continued need for pelvic exams since vaccine manufacturers will have a keen interest in the promotion of the virtues of vaccination but not the virtues of continued screening. In this respect, follow-up patient-systems must be put in place to ensure compliance (Bosch et al., 2008). It is important to note at this point in time that the changes in the practice settings will only be effective if some considerations are adequately met. Firstly, different people react differently to change and secondly, everyone has a fundamental need that has to be met. In addition, change may involve a loss in some way or the other. Nevertheless, expectations need to be managed realistically and fears of change need to be dealt with . In this light, when introducing change, people have to be given information in an open and honest way paying more attention to not giving overoptimistic speculations. For cases where larger groups are involved, a communication strategy should be put in place that ensures information is disseminated efficiently and comprehensively to everyone and if possible at the same time. The grapevine should not be allowed at any time to take over the dissemination of information. Most importantly, people should be given choices to choose from and there must be a degree of honesty about the possible consequences of those choices. 3.4 Sustainable Change Feasibility Ideally, the incorporation of vaccines into the system while maintaining effective screening programs will require healthcare infrastructure. This will include investing heavily in technology and manpower for such change to be effected. Health institutions do not operate in the vacuum, they co-exist in systems that rely on government and external funding. Therefore, programs can only become self-sustaining if there is a political goodwill to support the programs and maintain it with governmental funding after external support ends. Furthermore, without political support, it may be extremely difficult to cope with internal pressures to change decisions taken with regard to the programs since it is the politicians who pass policies that affect people’s lives (Bosch et al., 2008). In summary, for this sustainable change to be feasible, Bosch et al. (2008) have suggested that both professional and public need to renew and increase awareness on the burden of disease and the new opportunities for prevention and this will be achieved through education. Second, there is a need for financial support to continue the work initiated by a number of institutions and funding agencies have to ensure that support is being directed to make full use of these new opportunities. Lastly, the arrival of a new vaccine is a complex interdisciplinary exercise requiring different social abilities and expertise will require collaboration at a wide range to achieve success. 4. CONCLUSION Phase III clinical trails have reported in the interim results that HPV vaccines are effective in the prevention of HPV infections. This has been observed to be effective women between the ages of 14-26. Efforts are still underway to develop more multi-valent vaccines that will cover most of the HPV genotypes as well measuring the efficacy of vaccines in women over 26 years old. In addition, the vaccines have been suggested to be recommended for girls in their peri-puberty stages prior to the onset of sexual activities. There are still considerations to include boys and women in the vaccine programs to achieve herd immunity. However, against the backdrop of HPV vaccine development, screening still remains the best alternative for women who are already HPV sero-positive especially in developed countries as HPV vaccines are prophylactic and not cures and the fact that introducing vaccines in these countries where screening is effective will have various implications. To this respect there are calls for improving the current screening techniques and developing new generation techniques that will handle the challenges of screening especially in low-income countries. If vaccines and screening will be incorporated together in an effective program, then the efficacy of the program will produce 100% protection from HPV infections. Even though the journey is still long, what is important is that this journey has already begun. REFERENCES Belsey J., 2009. What is evidence-based medicine? London: Hayward Medical Communications. Bosch, F. X., Castellsague, X. and Sanjose, S., 2008. HPV and cervical cancer: screening or Vaccination? British Journal of Cancer 98: 15–21. Dunleavey, R., 2009. Cervical cancer: a guide for nurses. West Sussex, UK: John Wiley and Sons. Gallin, J. and Ognibene, P., 2002. Principles and practice of clinical research. 2nd Ed. Burlington, US: Elsever. Hulley, B. S., Cummings, S. R., Browner, W. S., Grady, G. D. and Newman, B. T. (2007). Designing clinical research. Philadelphia, PA: Lippincot Williams and Wilkin. Stanley, M., 2008. HPV vaccines: are they the answer? British Medical Bulletin. Vol. 88 Iss. 1 P. 59-74 Read More