<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

Abstract

Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPVrelated health issues. The approval of Gardasil ® as a prophylactic vaccine for high-risk HPV 16 and 18 and low-risk HPV6 and 11 for people aged 11-26 in 2006, and of Cervarix ® in 2009, revolutionized the field and has since reduced HPV infection in young populations. Unfortunately, prophylactic vaccination does not induce immunity in those with established HPV infections or HPV-induced neoplasms, and there are currently no therapeutic HPV vaccines approved by the US Food and Drug Administration. This comprehensive review will detail the progress made in the development of therapeutic vaccines against high-risk HPV types, and potential combinations with other immunotherapeutic agents for more efficient and rational designs of combination treatments for HPV-associated malignancies.

A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities

“…The development of therapeutic vaccines against hrHPV could help women who are already infected by stopping progression, triggering regression of lesions, and preventing recurrence of disease ( 166 ). Currently, there is no therapeutic HPV vaccine approved by the US Food and Drug Administration ( 167 ). While the use of therapeutic vaccines to treat invasive cervical cancer or other HPV-related cancers is beyond the scope of this review, many of the completed and currently ongoing trials (see NCT02481414, NCT00054041, NCT01022346, NCT03870113 as examples, not a comprehensive list) use CIN and/or HSIL as the treatment target.…”

“…While the use of therapeutic vaccines to treat invasive cervical cancer or other HPV-related cancers is beyond the scope of this review, many of the completed and currently ongoing trials (see NCT02481414, NCT00054041, NCT01022346, NCT03870113 as examples, not a comprehensive list) use CIN and/or HSIL as the treatment target. Smalley Rumfield et al recently conducted a review of peptide, protein, viral vector, bacterial vector, cell, DNA, and RNA-based therapeutic vaccines as well as multi-platform and combination therapies, which demonstrate diverse potential therapies that can be useful in LMIC settings, while presenting new and different challenges ( 167 ).…”

Transition metal-catalysed A-ring C–H activations and C(sp2)–C(sp2) couplings in the 13α-oestrone series and in vitro evaluation of antiproliferative properties

“…This test compound, exerting outstanding activity against both HPV-18 and HPV-16 positive cervical cancers, might be of great importance in the design of anticancer agents targeting cervical carcinomas, since the majority of these carcinomas are caused by these two types of HPV. For invasive cervical cancer, HPV-16 is the most prevalent type (approximately 60%), HPV-18 is the second (15%), and HPV-45 is the third most common type 65 .…”

A Systematic Review of MicroRNAs Involved in Cervical Cancer Progression

“…Low-risk HPV types are those that cause genital warts but are not carcinogenic, including types 6,11,42,43, and 44 [16,18]. High-risk HPV types are considered carcinogenic, and include 16,18,31,33,34,35,39,45,51,52,56,58,59,66,68, and 70 [6,16]. Wentzensen et al [19] confirmed that HPV integration sites are randomly distributed over the whole genome, with a clear predilection for fragile sites.…”

“…Based on their association with cervical cancer and precursor lesions, HPVs can also be grouped into high-risk and low-risk HPV types. Low-risk HPV types are those that cause genital warts but are not carcinogenic, including types 6, 11, 42, 43, and 44 [ 16 , 18 ]. High-risk HPV types are considered carcinogenic, and include 16, 18, 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 70 [ 6 , 16 ].…”