Table 3.

Oncolytic viruses being exploited for treatment of cervical cancer.

Virus	Description	Mechanism	Clinical Condition	Reference
Adenovirus	Non-enveloped virus with 90–100 nm size, have icosahedral nucleocapsid, which contain double-stranded DNA genome	Target tumor antigens specifically. Different Ad virus species bind with different receptors including CAR, αvβ5 integrin, HSPG, VCAM-1, MHC-Iα2	ONYX-015 (FDA-approved in China) is used in synergy with standard chemotherapy agents 5-fluorouracil and cisplatin to treat head and neck squamous carcinoma. Another virus similar to Onyx-015 (E1B-55K/E3B-deleted), H101 is tested promising for use in combination with radiation therapy to treat metastatic cervical cancer.	[60] [61]
Newcastle Disease virus	Single-stranded, negative sense, enveloped RNA virus. Causes contagious bird disease	Targeted replication in interferon-defective cancer cells by binding with Sia receptors on tumor cells. Avoids problem of pre-existing immunity	NDV selectively kills cervical cancer cells by inducing ROS-mediated apoptosis. NDV triggers both innate and adaptive immune response in cervical cancer TME by causing inflammation and recruitment of CD4+ and CD8+ immune responses.	[62]
Vaccinia virus	Linear double-stranded DNA genome containing enveloped virus. Approx 360 × 270 × 250 nm in size	Can squeeze through leaky tumor vascular for targeted infection tumor cells. Binds with MARCO receptor (macrophage receptor with collagenous structure)	It has been reported that oncoVV (vaccinia varus) encoding AVL Aphrocallistes vastus lectin (AVL) genes enhanced the cytotoxic effect of oncolytic vaccinia virus (oncoVV) in cervical cancer both in vitro and in vivo.	[63]
Herpes simplex virus(HSV)	Linear, double stranded DNA genome virus with approximately 152 kbp length	Binds with at least 3 receptors which are over expressed/abnormally expressed on cancer cells. Receptors are HVEM, nectin-1 and 3-OS-HS.	As reported, triple-mutated, third-generation HSV therapy was targeted for HPV16- or HPV18-associated cervical carcinoma in which human Hela xenograft and TC-1 syngeneic models were studied. It was found that oncolytic HSV greatly inhibited cervical tumor growth, mediated apoptosis, and turned cervical cancer tumor “hot” for immune targeting.	[64]