Human Papillomavirus Vaccination and Screening in the Elimination of HPV- Associated Cancers Evidence Base from Randomized Trials E-Book
31,67 €
Mehr erfahren.
- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Human Papillomavirus Vaccination and Screening in the Elimination of HPV-Associated Cancers: Evidence Base from Randomized Trials explores cutting-edge strategies for eliminating HPV-associated cancers through vaccination and screening, showcasing findings from rigorous, evidence-based randomized trials. Key topics include the causative role of HPV in cancers, the effectiveness and safety of HPV vaccines, and the profound impact of gender-neutral vaccination programs. The book also covers innovative screening methods for vaccinated populations, addressing cervical and oropharyngeal cancers. Aimed at healthcare professionals, researchers, and students, this book provides crucial insights into the global efforts to combat HPV and its associated cancers.
Key Features:
- In-depth analysis of HPV’s role in cancer causation.
- Comprehensive coverage of HPV vaccine efficacy and safety.
- Evaluation of gender-neutral vaccination impact on public health.
- Advanced screening methods for cervical and oropharyngeal cancers in vaccinated individuals.
- Data-driven recommendations for the future of HPV cancer prevention.
Readership: Suitable for undergraduate and graduate students, healthcare professionals, and researchers.
Das E-Book können Sie in Legimi-Apps oder einer beliebigen App lesen, die das folgende Format unterstützen:
Seitenzahl: 376
Veröffentlichungsjahr: 2024
Ähnliche
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
This is an agreement between you and Bentham Science Publishers Ltd. Please read this License Agreement carefully before using the book/echapter/ejournal (“Work”). Your use of the Work constitutes your agreement to the terms and conditions set forth in this License Agreement. If you do not agree to these terms and conditions then you should not use the Work.
Bentham Science Publishers agrees to grant you a non-exclusive, non-transferable limited license to use the Work subject to and in accordance with the following terms and conditions. This License Agreement is for non-library, personal use only. For a library / institutional / multi user license in respect of the Work, please contact: [email protected].
Usage Rules:
All rights reserved: The Work is the subject of copyright and Bentham Science Publishers either owns the Work (and the copyright in it) or is licensed to distribute the Work. You shall not copy, reproduce, modify, remove, delete, augment, add to, publish, transmit, sell, resell, create derivative works from, or in any way exploit the Work or make the Work available for others to do any of the same, in any form or by any means, in whole or in part, in each case without the prior written permission of Bentham Science Publishers, unless stated otherwise in this License Agreement.You may download a copy of the Work on one occasion to one personal computer (including tablet, laptop, desktop, or other such devices). You may make one back-up copy of the Work to avoid losing it.The unauthorised use or distribution of copyrighted or other proprietary content is illegal and could subject you to liability for substantial money damages. You will be liable for any damage resulting from your misuse of the Work or any violation of this License Agreement, including any infringement by you of copyrights or proprietary rights.Disclaimer:
Bentham Science Publishers does not guarantee that the information in the Work is error-free, or warrant that it will meet your requirements or that access to the Work will be uninterrupted or error-free. The Work is provided "as is" without warranty of any kind, either express or implied or statutory, including, without limitation, implied warranties of merchantability and fitness for a particular purpose. The entire risk as to the results and performance of the Work is assumed by you. No responsibility is assumed by Bentham Science Publishers, its staff, editors and/or authors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products instruction, advertisements or ideas contained in the Work.
Limitation of Liability:
In no event will Bentham Science Publishers, its staff, editors and/or authors, be liable for any damages, including, without limitation, special, incidental and/or consequential damages and/or damages for lost data and/or profits arising out of (whether directly or indirectly) the use or inability to use the Work. The entire liability of Bentham Science Publishers shall be limited to the amount actually paid by you for the Work.
General:
Any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims) will be governed by and construed in accordance with the laws of Singapore. Each party agrees that the courts of the state of Singapore shall have exclusive jurisdiction to settle any dispute or claim arising out of or in connection with this License Agreement or the Work (including non-contractual disputes or claims).Your rights under this License Agreement will automatically terminate without notice and without the need for a court order if at any point you breach any terms of this License Agreement. In no event will any delay or failure by Bentham Science Publishers in enforcing your compliance with this License Agreement constitute a waiver of any of its rights.You acknowledge that you have read this License Agreement, and agree to be bound by its terms and conditions. To the extent that any other terms and conditions presented on any website of Bentham Science Publishers conflict with, or are inconsistent with, the terms and conditions set out in this License Agreement, you acknowledge that the terms and conditions set out in this License Agreement shall prevail.Bentham Science Publishers Pte. Ltd. 80 Robinson Road #02-00 Singapore 068898 Singapore Email: [email protected]
FOREWORD
In 2024, the world is on the brink of eliminating formerly common forms of human cancer, in particular cervical cancer. The story of how this happened contains many lessons to be learned on how a major public health improvement could eventually be accomplished. Professor emeritus Matti Lehtinen has with an incredible persistence pursued original research on this subject since the 1970s. An overarching theme has been that the adoption of new scientific concepts requires a maximally reliable evidence base. Already in the 1970:ies the Nobel Prize winner Harald Zur Hausen proposed that a new type of HPV could be the long-sought infectious cause of cervical cancer. After his discovery of the most important oncogenic HPV (HPV16) in 1983 and the completion of worldwide surveys and a large cohort study of HPV and cervical precancer in 1987, it would seem like the stage was set to eliminate the cancers caused by HPV. However, it would take some 4 decades of careful science to arrive at the goal.
A book by a researcher who has been actively working with this task ever since is a much-needed documentation of the key issues that must be addressed to achieve progress and also how to address them. The starting point is longitudinal cohort studies to establish etiology. This work had to start with first debunking earlier myths of herpes viruses as the cause of cervical cancer. Weak case-control studies had resulted in erroneous conclusion that kept being popular for many years until finally proven incorrect by prospective studies, a lesson on the need for strong study designs in etiological research that is worth contemplating for anyone interested in the correct etiology of diseases. HPV readily stood the test - prospective studies found it to be a strong risk factor for both cervical, anal, vulvar, vaginal, penile and oropharyngeal cancers.
The next phase was the evaluation of the safety and efficacy of HPV vaccines. When such trials were planned, there were important discussions regarding exactly what evidence would be needed. Repeatedly, there was a minority of only one person (Matti Lehtinen) who insisted on that the maximally reliable study design – randomized trials with invasive cancer as an endpoint - would be needed. As a result, such trials were performed only in Finland. With hindsight, it must be said that -although the final result of such trials took many years to complete - the fact that such studies were indeed performed and showed such strong cancer protection, is a very valuable basis for global elimination efforts.
The issue of which strategy to use for HPV vaccination is still being debated even to this day. Basic science and experiences from other vaccination programs clearly favored vaccination of both genders. However, the vaccination of only girls requires only half as many vaccine doses. Again, the assessment was that debates and predictions could probably continue for ever without reaching a clear consensus. Maximally reliable evidence from randomized trials of vaccination of girls only or vaccination of both genders would be required. Again, Finland is the only country that has provided the world with such evidence from the trials of Matti Lehtinen et al.
A stumbling block in many assessments of how to design a vaccination program is assessing the probability of type replacement. The concept means that if one virus type is eliminated by vaccination, some other type could appear. At one time, there was a plethora of uninformed studies on this subject. The concept described in the book is that this phenomenon could not possibly be seen before vaccine-targeted HPV types are near-eliminated in the population and that communities, where the vaccination strategy that achieves fastest HPV elimination (gender-neutral vaccination) has been used, would be the populations where the phenomenon could best be quantified. As presented in the book, the phenomenon is indeed seen but has qualifications that suggest that it will not be of importance to public health.
The next issue to tackle was the need for cervical screening. The fact that cervical screening was introduced without any randomized trials as evidence base has hampered the development of optimal public health policies for many decades. In the future, if and when the necessary risk factor for cervical cancer (HPV) is missing, it is no longer meaningful to continue with cervical screening as before, particularly as the screening program is not devoid of side effects. The assessment here was that, as these screening programs have been performed for >60 years, policies and procedures were likely to be firmly entrenched and change would probably not occur unless maximally reliable evidence was provided by randomized trials. As far as I know, there are no other randomized trials of reducing screening in the world and the efforts that Matti Lehtinen describes are therefore both innovative and of obvious public health importance.
The final chapter deals with a very frequently asked question, namely “Once cervical cancer is eliminated, which other cancer form is next in line for elimination?”. The obvious answer is HPV-associated oropharyngeal cancers that in Western countries are responsible for almost as many deaths as cervical cancers. During the times when HPV infection was common, HPV-based screening for oropharyngeal cancers was not realistic. However, in the era where HPV is nearly eliminated, the predictive values of HPV screening for oropharyngeal cancer will increase, and the development and evaluation of new screening modalities that could be used for the elimination of oropharyngeal cancer might result in that also this major form of human cancer becomes slated for elimination.
In summary, this comprehensive narrative on how an important evidence base for cervical cancer elimination was obtained is important to understand the development of a new concept for public health. The forward-looking chapters on how science could promote a switch from unnecessary over-screening for cervical cancer to a new screening program for oropharyngeal cancer puts forward a vision for the future that should be of interest to anyone interested in cancer.
PREFACE
I have been involved with studies on the causes and control of cervical neoplasia for close to 45 years. Evidence that helps rejecting the non-causal association between herpes simplex virus type 2 (HSV-2) and cervical cancer [1-3], and confirms the association between previous infection with human papillomavirus type 16 (HPV16) and development of cervical cancer later in life [4, 5] emerged 30-40 years ago. Like other cancers, cervical cancer is a multi-etiological disease. In a number of our cohort studies it was possible to set order among independent pieces of the puzzle like smoking [6] and infection with Chlamydia trachomatis [7], or interacting pieces like non-oncogenic HPV types 6/11 [8, 9] and HLA-type [10]. Chapter I of this book ends with a suggestion: Data from our Nordic cohort study setting that successfully participated in dissolving the etiology of cervical cancer should now be used to evaluate the performance of artificial intelligence in causal inferencing up to change of paradigma. This is now timely also to understand and tackle the cervical cancer epidemic that has been ongoing among fertile-aged Finnish women over the last 25 years [11].
Prophylactic vaccination against a defined infectious cause of human cancer followed by elimination of the cancer is not only the ultimate proof of related causality, but also the most efficient means to alleviate, even abolish the given infection-associated cancer-burden. Proving hepatitis B-virus (HBV) vaccine efficacy against hepatocellular carcinoma took 25 years [12]. Our active, from the beginning population-based, participation to phase II to phase IV trials that involved HPV-vaccine development, licensure, and implementation of HPV vaccination have produced safety, immunogenicity and efficacy data for both the bivalent and quadrivalent vaccines (for a review see Lehtinen and Dillner [13]). Besides providing reliable and uniquely sensitive safety data our population-based approach with health-registry linkages provided long-term (up to 15 years) immunogenicity follow-up for a head-to-head comparison of the licensed HPV vaccines [14, 15]. First evidence on the efficacy of the HPV vaccine against human cancer was provided, this time in 10 years from the vaccine licensure [16] and also from the above-mentioned population-based setting as described in Chapter II.
The bivalent and quadrivalent HPV vaccines were the first highly efficacious vaccines licensed against sexually transmitted infections and their sequelae, including HPV-associated immediate precancerous lesions [17-21]. The implementation of these vaccines into national vaccination programs has, however, been a disappointment with global HPV vaccination coverage in the targeted female age-groups being 12%, and not more than 43% in high-income countries, where vaccine price should not be an issue [22]. It is obvious that the WHO campaign to eliminate cervical cancer by 2030 is bound to fail unless new scientifically sound approaches are soon implemented. Chapter III describes in detail the Finnish community-randomized trial on the impact of different HPV vaccination strategies. Comparing the gender-neutral and girls-only vaccination of early adolescent birth cohorts we have proven the superb effectiveness of gender-neutral vaccination in the introduction of herd effect against HPV types 16/18/31/33/35 in less than four years post-vaccination [23-25].
Following already moderate gender-neutral HPV vaccination coverage, the ecological niche of the vaccine HPV types 16/18 becomes essentially vacated in four to eight years [26]. Various epidemiological approaches to identify the replacement of the vaccine types with non-vaccine, high-risk HPV types either in vaccinated women [27, 28] or unvaccinated women [29-31] have been unequivocal to say the least. This may have been because of the extremely short follow-up time for a single non-vaccine HPV type to take over the vacated ecological niche [32]. However, an ecological approach managed to disclose abrupt changes in the overall HPV type-distribution and documented replacement of HPV-vaccine types in the vacated ecological niche already four years post gender-neutral vaccination [26]. Chapter IV elaborates on how and why the ecological tools used were more suitable than conventional epidemiological tools when trying to disclose what was and is happening in the HPV population biology following prophylactic vaccination.
There is an imminent danger that the Swiss cheese model applies to preventative measures against cervical cancer. Females, who do not get vaccinated as adolescents are prone to be the least active participants in organized cervical cancer screening [33]. However, the HPV vaccination-derived herd effect extends protection also to the marginalized females. Besides the remaining high-risk HPV types identified in cervical lesions of the fully vaccinated sexually active population may have considerably lower progression potential [34, 35]. Chapter V elaborates on new possibilities in HPV-independent triage of cervical precancer in HPV-vaccinated women and women, who have been under herd protection and acquired cervical infections from non-vaccine HPV types only [35].
Non-cervical HPV-associated cancers comprise one of the last black boxes in terms of population-attributable fractions of vaccine HPV types. Especially, the rapidly increasing HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) calls for attention since it is already now as common as cervical cancer in a number of Western countries [36], and in the foreseeable future in a number of other countries as well. While prophylactic vaccination of HPV naïve birth cohorts is the ultimate solution also to HPV-associated OPSCC there are 30 to 50 young adult and middle-aged, most notably male birth cohorts that would benefit from effective screening of the disease. Most likely due to the anatomic location of the tumour, serological screening of HPV-OPSCC is possible due to the early appearance of HPV16 E6 protein antibodies 10 to 30 years before clinical diagnosis of the tumour. Chapter VI describes in detail the planned screening trial that again makes use of the Finnish cohort study setting with serum samples to be screened, which had already been taken 10 to 30 years ago [37].
In the post-vaccination era, when gender-neutral HPV vaccination has been implemented we are approaching the eradication of the most important oncogenic HPV types [11, 23]. This is qualitatively different from the WHO-pursued [38] elimination of cervical cancer below a certain low incidence (4/100.000) threshold. Finland is a striking example of how easily a country can slide above these arbitrary incidence thresholds. [11, 39]. How to reliably document impact and sustainability of such different public health interventions as prophylactic HPV vaccination, and screening and treatment of precancerous cervical lesions has not been solved yet [22]. On the contrary, the resilience of prophylactic HPV vaccination programs is being assessed as elaborated in the Endgame chapter.
Etiological Studies on Cervical Neoplasia – A Showcase of Causal Inferencing
Matti LehtinenAbstract
Preventive medicine is largely about identification of causes of diseases and their removal. Cervical cancer in Finland is firstly a showcase and secondly a use-case of preventive medicine. Firstly, etiological studies on cervical cancer were for long confounded by the fact that sexually transmitted infections are surrogates of both risk-taking behaviour in adolescent and young adult population, and occurrence of cervical cancer in middle-aged women. Identifying oncogenic human papillomaviruses (HPVs) as the true cause of cervical cancer among the multitude of different sexually transmitted micro-organisms required a Nobel-prize winning vision which was initially supported only by case-series evidence. It also required a paradigm shift that was facilitated by a correctly done epidemiological study and increased understanding on the molecular basis of exposure misclassification. All this was understood only after the etiological enigma had been resolved. Secondly, since the sexual revolution in 1960’s first facilitated increase in risk-taking sexual behaviour associated sexually transmitted infections’ incidence, and subsequently resulted in an increase in the incidence of cervical cancer. In the below Finnish use-case, the role of different causal (HPV16/18/31/45), intervening (Chlamydia trachomatis, smoking, HLA, HPV6/11) and non-causal (herpes simplex virus type 2) factors are put into perspective based on longitudinal, population-based studies. The established evidence base is now available for the evaluation of artificial intelligence/ machine learning performance in disclosing and judging causes of a chronic disease, cervical cancer.
