*Review* **Targeting Human Papillomavirus-Associated Cancer by Oncoprotein-Specific Recombinant Antibodies**

**Maria Gabriella Donà 1, Paola Di Bonito 2, Maria Vincenza Chiantore 2, Carla Amici 3,† and Luisa Accardi 2,\*,†**


**Abstract:** In recent decades, recombinant antibodies against specific antigens have shown great promise for the therapy of infectious diseases and cancer. Human papillomaviruses (HPVs) are involved in the development of around 5% of all human cancers and HPV16 is the high-risk genotype with the highest prevalence worldwide, playing a dominant role in all HPV-associated cancers. Here, we describe the main biological activities of the HPV16 E6, E7, and E5 oncoproteins, which are involved in the subversion of important regulatory pathways directly associated with all known hallmarks of cancer. We then review the state of art of the recombinant antibodies targeted to HPV oncoproteins developed so far in different formats, and outline their mechanisms of action. We describe the advantages of a possible antibody-based therapy against the HPV-associated lesions and discuss the critical issue of delivery to tumour cells, which must be addressed in order to achieve the desired translation of the antibodies from the laboratory to the clinic.

**Keywords:** antibody therapeutics; recombinant antibodies; intracellular antibodies; single-chain antibody fragment; nanobody; Human papillomaviruses; HPV oncoproteins; HPV-associated cancer; HPV cancer therapy
