Molecular Aspects of Medicine

Vaccines for HPV-associated diseases

Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions. Unlike prophylactic vaccines, which act to prevent HPV infection, therapeutic vaccination presents an opportunity to induce cellular immunity against established HPV infections and lesions and prevent progression to cancer. Several HPV vaccines are undergoing clinical development, using a range of platforms. Peptide- or protein-based vaccines, vector-based vaccines, whole-cell vaccines, and nucleic acid vaccines each offer relative merits and limitations for the delivery of HPV antigens and the subsequent generation of targeted immune responses. There has been particular interest in DNA-based vaccines, which elicit both cellular and humoral immune responses to provide long-lasting immunity. DNA vaccines offer several practical advantages over other vaccine platforms, including the potential for rapid and scalable manufacturing, targeting of many different antigens, and potential for repeat boosting. Furthermore, unlike vectored approaches, DNA vaccines are thermostable over extended time periods, which may enable shipping and storage. Several delivery strategies are available to address the main challenge of DNA vaccines, namely their relatively low transfection efficiency. We review the latest clinical data supporting the development of DNA vaccines and reflect on this exciting prospect in the management of HPV-related disease.

Elimination of cervical cancer: the impact of HPV vaccination, primary HPV screening, and expanded access to cancer treatment services

In 2022, over 662,000 cases of cervical cancer were diagnosed globally and over 348,000 deaths occurred from the disease, with almost 94 % of these deaths occurring in low- and lower-middle income countries (LMIC). Effective intervention strategies, including prophylactic Human Papillomavirus (HPV) vaccination for adolescents and primary HPV screening for adult women, are highly effective and cost-effective methods of prevention; however, delivering population-wide access to these prevention methods has been challenging, particularly in LMIC. The World Health Organization (WHO) has launched a global strategy for the elimination of cervical cancer as a public health problem through the scale-up of HPV vaccination, cervical screening and precancer and cancer treatment services. In this review article, we present the rationale, history and strategy behind the global cervical cancer elimination efforts, including the evidence underpinning the WHO's three pillars of cervical cancer control, and essential considerations for implementation, sustainable financing, and health systems implications. Many countries and regions are currently formulating frameworks to achieve cervical cancer elimination within their setting. Here, we consider implementation challenges for both LMIC, and high-income countries (HIC), calling upon the experiences of implementation guided by the WHO Western Pacific Region and Australian frameworks as exemplar settings.

Nanoparticle-aided glycovariant assays to bridge biomarker performance and ctDNA results

Numerous immunoassay based cancer biomarkers established in the 1970 and 1980'ies are widely used in clinical routine. Initial expectations of biomarkers such as CEA, CA125, CA19-9, AFP to provide decisive help in the diagnosis of early stage, pre-symptomatic cancers have not been realized. Thus, they are primarily used for monitoring disease progression and occasionally being useful as prognostic indicators. This limitation is due to the marker also being measurable in healthy individuals and frequently at elevated concentrations in common benign conditions. Most conventional tumor markers are glycosylated and interestingly specific alterations of the glycostructure part can often be seen early in the cancerous process. Conventional double monoclonal immunoassays are however blind to such changes as they are based on peptide epitope recognition. Wide selections of carbohydrate recognizing macromolecules, lectins, but also glycan structure recognizing antibodies are potentially useful for detecting such changes. Despite numerous attempts generating proof-of-principle evidence for this, such assays have generally not been successfully introduced into clinical routine. The affinity constants of lectin and glycan specific antibodies for their corresponding carbohydrate structures may be up to several orders too low to provide the detection limits and robustness expected from routine tumor markers. In this review, we describe an approach based on the use of highly fluorescent Eu