Abstract
Infection with human papillomavirus (HPV) is one of the main causes of malignant neoplasms, especially cervical, anogenital, and oropharyngeal cancers. Although we have developed preventive vaccines that can protect from HPV infection, there are still many new cases of HPV-related cancers worldwide. Early diagnosis and therapy are therefore important for the treatment of these diseases. As HPVs are the major contributors to these cancers, it is reasonable to develop reagents, kits, or devices to detect and eliminate HPVs for early diagnosis and therapeutics. Immunological methods are precise strategies that are promising for the accurate detection and blockade of HPVs. During the last decades, the mechanism of how HPVs induce neoplasms has been extensively elucidated, and several oncogenic HPV early proteins, including E5, E6, and E7, have been shown to be positively related to the oncogenesis and malignancy of HPV-induced cancers. These oncoproteins are promising biomarkers for diagnosis and as targets for the therapeutics of HPV-related cancers. Importantly, many specific monoclonal antibodies (mAbs), or newly designed antibody mimics, as well as new immunological kits, devices, and reagents have been developed for both the immunodiagnosis and immunotherapeutics of HPV-induced cancers. In the current review, we summarize the research progress in the immunodiagnosis and immunotherapeutics based on HPV for HPV-induced cancers. In particular, we depict the most promising serological methods for the detection of HPV infection and several therapeutical immunotherapeutics based on HPV, using immunological tools, including native mAbs, radio-labelled mAbs, affitoxins (affibody-linked toxins), intracellular single-chain antibodies (scFvs), nanobodies, therapeutical vaccines, and T-cell-based therapies. Our review aims to provide new clues for researchers to develop novel strategies and methods for the diagnosis and treatment of HPV-induced tumors.
Highlights
Every year, more than 4.5% (8.6% in women and 0.8% in men) of all cancers worldwide (630,000 new cancer cases), such as cervical cancer, vulvar cancer, vaginal cancer, penile cancer and anal cancer 1), oropharyngeal cancers (OPC; including tumors derived from the base of the tongue and tonsils), and even esophageal adenocarcinoma (EAC) [2, 3], are attributed to the human papillomaviruses (HPVs) (Figure 1)
Two mouse mAbs induced by a recombinant HPV16 E7 oncoprotein were used to establish a chemiluminescent immunoassay based on a labeled streptavidinbiotin (LSAB)- enzyme-linked immunosorbent assay (ELISA) method and a luminol detection system that was suitable for the detection of HPV16 E7 oncoprotein in HPV16-positive cervical carcinoma tissues
VLPs were tested by ELISA for detecting antibodies in the sera of HPV 16 in women with cervical cancer and cervical intraepithelial neoplasia (CIN), and the results showed that this assay using HPV16 VLP may be useful as a diagnostic tool to supplement cervical cytological tests [77]
Summary
More than 4.5% (8.6% in women and 0.8% in men) of all cancers worldwide (630,000 new cancer cases), such as cervical cancer, vulvar cancer, vaginal cancer, penile cancer and anal cancer 1), oropharyngeal cancers (OPC; including tumors derived from the base of the tongue and tonsils), and even esophageal adenocarcinoma (EAC) [2, 3], are attributed to the human papillomaviruses (HPVs) (Figure 1). HPVs are a kind of small, unenveloped, and highly host-specific double-stranded circular DNA viruses [6]. They are microorganisms that are sexually transmitted via genital contact and a kind of viruses that can be passed on by skin and mouth [7]. The genome of 189 HPV types have been completely sequenced. According to DNA sequence analysis, HPVs have been divided into five genera—a, b, g, Nu, and Mu—each with different life cycle characteristics and related diseases [8,9,10]. Epidemiological studies show that HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 are carcinogenic, and HPV68 are probably carcinogenic [6]. HPV16 is the most prevalent worldwide and the major cause of HPV-associated cancers [11]
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