A conversion formula was applied to translate these protein-protein interaction energies to a comparable scale for non-protein interactions, further underscoring the superior binding potential of apigenin and luteolin. These findings highlight the therapeutic promise of these natural compounds in preventing HPV-16-induced oncogenesis, warranting further experimental validation for clinical applications.

P2, N=35, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting | N=80 --> 35 | Trial completion date: Sep 2029 --> Jan 2027 | Trial primary completion date: Sep 2029 --> Jan 2026

Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

P2, N=18, Active, not recruiting, Dan Zandberg | Recruiting --> Active, not recruiting | N=50 --> 18 | Trial completion date: Jun 2027 --> Jun 2026 | Trial primary completion date: Jun 2027 --> Jun 2025

P=N/A, N=150, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi

Our study demonstrated HPV viral mutations are closely related to host gene epigenetic alterations in CC. Integration of the viral and host genetic information might be a new promising strategy for CC screening.

P2/3, N=450, Not yet recruiting, Hookipa Biotech GmbH

The primary objective is to assess the disease-free survival (DFS) for pts enrolled in the study receiving either HB-200 or placebo. The secondary objectives include overall survival, and safety.

P2, N=41, Terminated, M.D. Anderson Cancer Center | N=77 --> 41 | Active, not recruiting --> Terminated; Project delays

P1, N=12, Recruiting, ImmunityBio, Inc. | Not yet recruiting --> Recruiting | N=18 --> 12 | Trial primary completion date: Dec 2024 --> Sep 2025

Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.

P1/2, N=24, Recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2; Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

The percentage of CD8+ T cells decreased. HPV16-E6-E7-Rosa26 induced low immune function in mice, and provides a good model for the basic research of the mechanisms of action of HPV infection-associated precancerous lesions or cervical cancer.

P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Mar 2024 --> Jun 2025

However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.

Results from this phase 2 study of cemiplimab + ISA101b in patients with recurrent HPV16 cervical cancer show clinical benefit, especially in patients with high PD-L1 expression, and no unexpected safety signals, supporting further research.

"Naveris, Inc...announced the launch of a Phase II clinical study in minimal residual disease positive (MRD+) HPV-driven head and neck cancer. The study will be led by Memorial Sloan Kettering Cancer Center (MSKCC), a top cancer treatment and research institution. The primary objective of this multicenter randomized study is to evaluate the efficacy of HB-200, a novel intervention, for patients with HPV16+ head and neck squamous cell cancer (HNSCC) with molecular relapse, defined as the presence of circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA without clinical or radiographic evidence of recurrence following definitive treatment."

P2, N=51, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=18, Recruiting, TCRCure Biopharma Ltd. | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=24, Not yet recruiting, Corregene Biotechnology Co., Ltd

P1/2, N=150, Active, not recruiting, Transgene | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=18, Not yet recruiting, ImmunityBio, Inc. | Initiation date: Mar 2024 --> Jun 2024

P1/2, N=20, Terminated, SQZ Biotechnologies | N=60 --> 20 | Trial completion date: Mar 2024 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Nov 2023; Corporate Decision

The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

P1/2, N=32, Completed, University of Southampton | Active, not recruiting --> Completed

According to our results, in the E6 knock out (E6KO) cell lines an increased expression of miR-143 was recorded, while a decrease in the expression of HIF-1a and PD-L1 was exhibited. These findings indicate that E6 protein probably plays a significant role in enabling cervical cancer cells to evade the immune system, while we propose a molecular pathway in cervical cancer, where PD-L1's expression is regulated by E6 protein through a miR-143/HIF-1a axis.

P2, N=22, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=35 --> 22 | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=65, Active, not recruiting, ISA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Jun 2024

P1, N=36, Not yet recruiting, NexImmune Inc. | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Jul 2024 --> Jul 2026

We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.

P2, N=194, Active, not recruiting, ISA Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=10, Terminated, Hookipa Biotech GmbH | N=27 --> 10 | Recruiting --> Terminated; Sponsor decision.

Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response...We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.

P2, N=285, Recruiting, BioNTech SE

P1/2, N=200, Recruiting, Hookipa Biotech GmbH

Our study demonstrates that PiwiL1 act as an oncogene in cervical cancer by inducing tumor-associated properties and EMT pathway. The finding that HPV oncogenes, E6/E7 can positively regulate PiwiL1 suggests a possible mechanism behind HPV-mediated tumorigenesis in cervical cancer.

P1/2, N=18, Recruiting, TCRCure Biopharma Ltd. | Trial primary completion date: Mar 2023 --> Dec 2023

P1/2, N=60, Active, not recruiting, SQZ Biotechnologies | Recruiting --> Active, not recruiting

"Forty-seven patients with cervical cancer were enrolled on this study between 2017 and 2022, either as part of a standard-of-care (SOC) treatment banking protocol (33 patients) or as part of a clinical trial combining a therapeutic HPV vaccine (PDS0101; Immunocerv, 14 patients)...Treatment with a therapeutic HPV vaccine was associated with a more rapid decline in cfHPV DNA. Further analysis of cfDNA kinetics could provide valuable information on the relationship between cfDNA levels, treatment response, and clinical outcomes."

HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively, expressing the same non-oncogenic HPV16 E7E6 fusion protein. Conclusions HB-200 monotherapy induces promising HPV16+ tumor-specific T cell responses and tumor infiltration in heavily pre-treated patients. This immune response coupled with clinical benefit in monotherapy suggests that HB-200 may enhance and strengthen current immunotherapy approaches by targeting specific tumor antigens.

On the other hand, higher expression of immune inhibitory molecules and HPV-16 E6E7 are cooperatively enhanced in CT-infected cells, which would favour both oncogenesis and immunosuppression. Our findings pose important implications for clinical management of patients with HPV and CT coinfection, suggesting that screening for the mutual infection could represent an opportunity to intervene and prevent severe reproductive health outcomes, such as cervical cancer and infertility.