Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Acting on the call: A framework for action for rapid acceleration of access to the HPV vaccination in low- and lower-middle-income countries.

Cervical cancer, caused by HPV infection, is responsible for more than 311  000 preventable deaths every year. A global call to accelerate efforts to eliminate this disease has generated a new global strategy proposing ambitious, but achievable, targets for HPV vaccination of girls, and screening and treatment of women. The present paper addresses the suboptimal access to HPV vaccination in low-income and lower-middle-income countries (LICs/LMICs), where the burden of disease weighs most heavily, in part through co-infection with HIV. A proposed framework for action was formulated by first reviewing the reasons underlying gaps in HPV vaccine coverage. Good practices from recent introductions of HPV vaccine at scale in LICs/LMICs were then assessed based on targeted literature reviews and the experience and views of the authors. Difficulties in uptake and coverage of the HPV vaccine relate to the costs of the vaccine and service delivery, lack of prioritization, the challenges of vaccinating adolescents, and shortage of vaccines as the supply failed to keep pace with the rapid expansion in global demand, including from LICs/LMICs. The framework for action calls for new strategic thinking to consolidate global learning and invigorate operationalization at a country level.

Cervical Precancer Treatment in Low- and Middle-Income Countries: A Technology Overview.

Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs). There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed.

Advocacy, communication, and partnerships: Mobilizing for effective, widespread cervical cancer prevention.

Both human papillomavirus (HPV) vaccination and screening/treatment are relatively simple and inexpensive to implement at all resource levels, and cervical cancer screening has been acknowledged as a "best buy" by the WHO. However, coverage with these interventions is low where they are needed most. Failure to launch or expand cervical cancer prevention programs is by and large due to the absence of dedicated funding, along with a lack of recognition of the urgent need to update policies that can hinder access to services. Clear and sustained communication, robust advocacy, and strategic partnerships are needed to inspire national governments and international bodies to action, including identifying and allocating sustainable program resources. There is significant momentum for expanding coverage of HPV vaccination and screening/preventive treatment in low-resource settings as evidenced by new global partnerships espousing this goal, and the participation of groups that previously had not focused on this critical health issue.