Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis

Abstract

Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.

Keywords: HPV-associated carcinogenesis; HPV-infection; immune evasion; immuno-pathogenesis; vaccination.

Figure 1

The structure of the HPV16 genome. The figure was modified and redrawn from [42].

Figure 2

HPV infection in the cervix, viral particles shedding and HPV protein expression. The figure was modified and redrawn from [44].

Figure 3

The figure presented a schematic representation of HR-HPV-inducing carcinogenesis. The figure was redrawn from [108].

Figure 4

HPV-related carcinogenesis hypothesis linking stromal cells, such as cancer-associated fibroblasts (CAF), myeloid-derived suppressor cells (MDSCs), etc., immune cells and keratinocytes. The figure was modified and redrawn from [136].