Human Papillomavirus (HPV) Vaccines Clinical Trials, Efficacy, Side Effects
The World Health Organization (WHO) recommends vaccinating against human papillomavirus (HPV) to prevent infections and associated cancers. As of October 2024, six licensed HPV vaccines protect males and females against cancers caused by HPV. These bivalent, quadrivalent, and nonavalent HPV vaccines are available in 140 countries. In the U.S., the U.S. Centers for Disease Control and Prevention (CDC) has recommended HPV vaccination for women since 2006 and for men since 2011. Current CDC HPV vaccination schedules were updated in 2024. HPV vaccine availability status in the U.S. is posted at View-Hub.
HPV Vaccines Approved
Gardasil -Merck's Gardasil® vaccine consists of 4 proteins of HPV types 6, 11, 16, and 18.
Gardasil 9 - Gardasil 9® consists of HPV proteins, Types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
Cervarix—GlaxoSmithKline's Cervarix is a non-infectious recombinant, AS04-adjuvanted vaccine that contains recombinant L1 protein, the major antigenic protein of the capsid of oncogenic HPV types 16 and 18.
Cecolin - Innovax Biotech Ltd.'s Cecolin HPV bivalent vaccine protects women against HPV 16 and 18. Cecolin 9 is a second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine.
Wa Biotechnology's recombinant bivalent HPV vaccine is effective against HPV strains 16 and 18. China's National Medical Products Administration approved it in March 2022.
Yuxi Zerun Biotechnology Co., Ltd. Walrinvax® two-dose HPV vaccine was approved in China in February 2024 and prequalified by the WHO in August 2024.
Cervavac is the Serum Institute of India's quadrivalent human papillomavirus vaccine (qHPV), authorized in India for 9-to 26-year-olds. Local availability began in 2023.
HPV Vaccine Candidates
PDS Biotech's Versamune® HPV (formerly PDS0101) is conducting multiple phase 2 studies in 2024.
RGVax - The U.S. FDA completed its review of the investigational new drug application for its licensed monovalent component HPV16 RG1-VLP and concluded that a Phase 1 clinical trial might proceed as of March 29, 2023. RGVax is a chimeric HPV VLP platform that displays 360 copies of the highly conserved, neutralizing HPV epitope. PathoVax LLC licensed the underlying RGVax foundational technology from Johns Hopkins University.
TG40 - Transgene'sene's TG4001 HPV16 vaccine candidate uses an attenuated and modified poxvirus as a vector expressing the HPV16 E6 and E7 proteins interleukin-2. Data presented on June 5, 2023, demonstrate Transgene's TG4001 could induce a specific immune response against the antigens vectorized within this vaccine.
Nykode Therapeutics announced positive results for the Phase IIa trial of its cervical cancer vaccine, VB10.16, delivered to 52 trial participants in combination with atezolizumab. Patients who received the vaccine were tracked for one year and showed a median overall survival of 16.9 months. A second, more extensive trial of VB10.16 in cervical cancer is set to begin in 2023.
VGX-31 - Inovio'svio's investigational immunotherapy vaccine includes DNA plasmids targeting the E6 and E7 proteins of HPV types 16 and 18.
INO-3107 - INOVIO announced positive interim results from an ongoing Phase 1/2 clinical trial evaluating INO-3107. The results showed a statistically significant improvement in the clinical endpoint of the number of surgical interventions needed to control papilloma growth. INO-3107 was also well-tolerated and immunogenic in the trial.
VTP-2 - Vaccitech'sech's ChAdOx1-HPV immunotherapy for high-risk HPV infection and low-grade cervical intraepithelial neoplasia. The platform has a differentiated ability to induce CD8+ T cells and cells of the immune system that naturally clear HPV-infected cells in cervical tissue. In addition, VTP-200 targets six early proteins from five high-risk HPV groups and, therefore, covers more types of HPV than any other immunotherapy previously tested. Data from the first 58 women enrolled who reached their 6-month timepoint in the HPV001 phase 1/2study were reviewed internally, and the trial will continue as planned to the 12-month primary endpoint.
HB-201 - HOOKIPA Inc.'s monotherapy is designed to use an arenavirus backbone (LCMV for HB- 201) while expressing the antigen, an E7/E6 fusion protein derived from HPV16+.
VB10.16 - Nykode Therapeutics is a potential first-in-class off-the-shelf therapeutic cancer vaccine in development to treat HPV16-positive cancers.
REC603 - Jiangsu Technology's REC603 is a recombinant HPV 9-valent vaccine conducting a phase 3 clinical trial. The REC604a is equipped with the novel adjuvanted BFA04 independently developed by the Company, which aims to reduce the vaccination dose by enhancing the immunogenicity and cross-protection effects.
Defence Therapeutics Inc. developed the AccuVAC-PT007, a protein-based vaccine targeting the E7 oncoprotein of the HPV virus.
LinKinVax is conducting a first-in-human Phase I/IIa clinical trial with CD40HVac, a new therapeutic vaccine candidate in immuno-oncology targeting dendritic cells against head and neck cancer associated with HPV. The first patient was dosed with CD40HVac for HPV-positive oropharyngeal cancer on September 18, 2023.
Genexine GX-188E (tirvalimogene teraplasmid) is a DNA therapeutic vaccine fused with encoding both E6 and E7 antigens and the extracellular domain of Flt3L to target and activate dendritic cells. A Multi-Center, Open-label Phase Ib-II Trial of the Combination of GX-188E Vaccination and Pembrolizumab in Patients with Advanced, Non-Resectable HPV-Positive Cervical Cancer.
PDS Biotechnology PDS0101 is a novel investigational HPV-targeted immunotherapy that stimulates a potent targeted T-cell attack against HPV-positive cancers. The VERSATILE-002 Phase 2 trial is for the treatment of recurrent or metastatic HPV16-positive head and neck cancer.
Precigen, Inc. presented PRGN-2009 AdenoVerse™ immunotherapy alone and in combination with an investigational anti-PDL1/TGF-Beta Trap checkpoint inhibitor in patients with recurrent/metastatic HPV-associated cancers (NCT04432597) in Abstract #2628.
Aston Sci. received Phase 2 Clinical Investigational New Drug approval from the U.S. FDA on September 12, 2023, for the AST-201 vaccine, which was explicitly designed for ovarian cancer.
HPV Vaccine Doses
The WHO's global recommendation for one-dose HPV vaccine schedules in 2022 significantly reduced barriers to scaling up vaccination programs. The Americas Region and the Regional Office for Africa also issued recommendations for the single-dose vaccination schedule. On April 11, 2022, WHO's Strategic Advisory Group of Experts on Immunization concluded that a single-dose HPV vaccine delivers virus protection comparable to 2-dose schedules. The UK's Joint Committee on Vaccination and Immunisation announced on August 5, 2022, that one HPV dose is as effective as two at preventing cancers caused by HPV in adolescents. The CDC's recommendations for 2 or 3 HPV vaccinations were updated in 2023.
HPV Vaccine Effectiveness
The Journal of the National Cancer Institute published results from a study in January 2024 that found no cases of invasive cancer were recorded in women in Scotland immunized at 12 or 13 years of age, irrespective of the number of bivalent vaccine doses. Women vaccinated at 14 to 22 years of age and given three doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 [95% confidence interval (CI) = 2.1 to 4.6] vs. 8.4 [95% CI = 7.2 to 9.6]).
A study published by the Journal of Infectious Diseases on October 12, 2023, found genital HPV infections within 24 months in about 40% (CI:33.4-48.4) of unvaccinated young women in new heterosexual relationships. Other sexually transmitted disease vaccine news is posted at this link.
Lauri E. Markowitz, M.D. Division of Viral Diseases, U.S. CDC Advisory Committee on Immunization Practices presented on June 23, 2022, which summarized: 'There are now data on 1-dose HPV vaccination, including efficacy data from a randomized controlled trial with 18-month follow-up. In addition, long-term follow-up from other studies suggests a good duration of protection (>10 years) with one dose. And Julia Gargano, Ph.D., presented: 'Impact of the US HPV vaccination program on HPV-associated outcomes. Declines in HPV16/18 prevalence have translated into declines in cervical precancer incidence in young women.'
A systematic review of 138 peer-reviewed studies, published between March 2016 and March 2020, within MEDLINE, EMBASE, and Google Scholar involving 14 years of follow-up data details the Impact and effectiveness of GARDASIL through immunization programs in 23 countries across Africa, Asia, Europe, Australia, South America, and North America. The most significant reductions were observed in younger age groups (14-17 years), with up to 73% reduction in CIN3+ among vaccinated females. Consistent with previous reviews, declines in the incidence of anogenital warts continue to be observed within vaccine-targeted female age groups, with more significant decreases (up to 88%) observed in younger age groups.
HPV Vaccination and HIV
A peer-reviewed study published on October 1, 2022, found MSM with HIV would benefit from Gardasil 9 immunization, particularly the youngest and those with prior gonococcal infection.
HPV Vaccination and Pregnant Women
HPV vaccination is not recommended for use by women during pregnancy.
HPV Cancer and Men
The Lancet Global Health pre-released a September 2023 report showing that almost 33% of men over 15 are infected with at least one genital HPV type, and 20% are infected with one or more high-risk or oncogenic HPV types.
HPV Cancers
In 2024, patients aged 65 and older had the largest increase (32.2%) in HPV diagnoses. The Global HPV Consortium focused on accelerating the prevention of HPV and eliminating cervical, throat, anal, and other HPV cancers, launched on September 4, 2023, and is led by the Sabin Vaccine Institute as its Secretariat. The Lancet Oncology reported in September 2023 that African countries are home to 19 of 20 countries with the highest burden of cervical cancer.
HPV Vaccine Cost
The HPV vaccine is the most expensive of all routinely recommended pediatric vaccines, reported a study in July 2023. This study found that net returns from HPV vaccine cost reimbursements are lowest for family physicians ($0.34/dose) and highest for pediatricians ($5.08/dose). Furthermore, reimbursement for HPV vaccine costs by private payers is adequate; however, return margins are small for non-pediatric specialties. The CDC reported in August 2023 that HPV vaccination initiation fell among adolescents insured by Medicaid and remained lowest among the uninsured, two of the four groups that constitute the Vaccines for Children population. The Vaccines for Children Program Vaccine Price List was updated in 2023.
Insight Partners stated that the HPV vaccine market is projected to reach $5.73 billion by 2028 and grow at a CAGR of 5% from 2022 to 2028. HPV vaccine prices and discount information are posted at InstantRx™.
CONTENT SOURCES: World Health Organization, US Centers for Disease Control and Prevention, FDA, research studies, manufacturer announcements, and the Precision Vax news network, reviewed by healthcare providers, such as Dr. Bob Carlson.
