Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications
Abstract
:Simple Summary
Abstract
1. Introduction
2. Overview of HPV Infection and Oncogenicity
3. Overview of HSV Infection
4. Relationship between HPV and Cervical Cancer
5. Relationship between HSV and Malignancy
Relationship between HSV and Cervical Cancer
6. Targeting HPV and HSV for the Prevention of Cervical Cancer
6.1. Prophylaxis and Early Detection of Oncogenic HPV
6.2. Prophylaxis and Treatment of HSV Infection
7. Recent Advances in Cervical Cancer Therapeutics
7.1. Systemic Therapies
7.2. Other Therapeutic Advances
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Study | Relationship Exists | Relationship Uncertain | Findings | Reference |
---|---|---|---|---|
McDougall et al. | X | Presence of HSV-2 RNA in cells undergoing pre-malignant changes; no evidence of HSV-2 RNA in squamous cell cancer cells | [159] | |
Li et al. | X | HSV-2 associated with the occurrence of cervical cancer; coinfection with both HPV and HSV-2 had a higher relative risk than either infection with HSV-2 or HPV alone | [160] | |
Bahena-Román et al. | X | Patients seropositive for HSV-2 had a higher risk of high-risk HPV; patients with high-risk HPV had a higher rate of active HSV-2 infection | [161] | |
de Abreu et al. | X | Increased risk of developing ≥ ASC-US cytology (initial cellular transformation) but not other cervical abnormalities such as HSIL. The authors concluded that HSV-2 may be involved in initial cellular transformation but not progression | [164] | |
DiPaolo et al. | X | Bg/II N region of HSV-2 converted immortalized genital epithelial cells into tumorigenic squamous cells | [15] | |
Pisani et al. | X | HSV-2 infection increased HPV gene expression of E1, E2 and E6 in HPV-16-infected cells | [165] | |
Paba et al. | X | HPV/HSV-2 coinfected cells overexpressed cellular protein survivin | [166] | |
Hara et al. | X | HSV-1 DNA polymerase could facilitate HPV-18 DNA replication | [167] | |
Koanga et al. | X | HSV-2 infection may induce cervical inflammation, potentially acting as a co-factor in cervical cancer formation | [168] | |
Okoye et al. | X | Immunocompromised status may facilitate viral-mediated oncogenesis | [169] | |
Cao et al. | X | Current evidence does not support the idea that HSV-2 plays a role in cervical cancer development | [174] | |
Lehtinen et al. | X | HSV-2 did not contribute to cervical cancer pathogenesis in Nordic countries | [175] | |
Ahmadi et al. | X | Only one instance of HSV-2 infection found out of 45 patients with cervical cancer | [14] | |
Joharinia et al. | X | No detection of HSV genomes in any patients diagnosed with low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, squamous cell carcinoma or adenocarcinoma of the cervix | [176] |
Drug | Mechanism of Action | References |
---|---|---|
Pembrolizumab | PD-1 inhibitor | [200,201,202,203] |
Nivolumab | PD-1 inhibitor | [204,205,206,213] |
Apatinib + camrelizumab | Apatinib: Tyrosine kinase inhibitor of VEGFR2 Camrelizumab: PD-1 inhibitor | [208] |
Ipilimumab | CTLA-4 inhibitor | [211,212,213] |
Nivolumab + ipilimumab | Nivolumab: PD-1 inhibitor Ipilimumab: CTLA-4 inhibitor | [213] |
Tisotumab vedotin | Antibody/drug conjugate targeting tissue factor | [215,216] |
Bevacizumab | Angiogenesis inhibitor | [217,218] |
Brachytherapy | Radiation | [223,224] |
SCRT v. CCRT v. RT | N/a | [225] |
Oncolytic viruses | Cytopathic and cytotoxic killing of tumor cells | [227,228,229,230] |
Vaccine therapies | Targeting E6/E7 | [81,231,232,233,234] |
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Sausen, D.G.; Shechter, O.; Gallo, E.S.; Dahari, H.; Borenstein, R. Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications. Cancers 2023, 15, 3692. https://doi.org/10.3390/cancers15143692
Sausen DG, Shechter O, Gallo ES, Dahari H, Borenstein R. Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications. Cancers. 2023; 15(14):3692. https://doi.org/10.3390/cancers15143692
Chicago/Turabian StyleSausen, Daniel G., Oren Shechter, Elisa S. Gallo, Harel Dahari, and Ronen Borenstein. 2023. "Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications" Cancers 15, no. 14: 3692. https://doi.org/10.3390/cancers15143692