Human Papillomavirus (HPV) Vaccines
Vaccination against human papillomavirus (HPV) is recommended to prevent new HPV infections and HPV-associated diseases, including cancers.
There are safe and effective HPV vaccines that can protect males and females against cancers caused by HPV. These vaccines include 9vHPV, 4vHPV, and/or 2vHPV, says the US Centers for Disease Control and Prevention (CDC).
The American Cancer Society updated its guideline for HPV vaccination on July 8, 2020. The new recommendations are for healthcare providers to routinely offer the HPV vaccine series to boys and girls between ages 9 and 12.
A study published by the NEJM on October 1, 2020, found among Swedish women between 10 to 30 years old, the quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level.
HPV Preventive Vaccines - Approved
Gardasil - Merck's Gardasil vaccine consists of 4 proteins of HPV types 6, 11, 16, and 18. Gardasil is highly efficacious in preventing infection from virus types 16 and 18, which are together responsible for approximately 70% of cervical cancer cases globally. The quadrivalent vaccine is also highly efficacious in preventing anogenital warts, a common genital disease that is virtually always caused by infection with HPV types 6 and 11.
Gardasil 9 - Gardasil 9 consists of HPV proteins, Types 6, 11, 16, 18, 31, 33, 45, 52, and 58. HPV infections can lead to certain cervical cancers. Many females with cervical cancer were probably exposed to cancer-causing HPV types in their teens and early 20s. Additionally, males can get HPV, causing anal and throat cancers and genital warts.
Cecolin - Innovax's Cecolin HPV Vaccine protects women against HPV 16 and 18, two HPV types causing 70 percent of all cervical cancers, the third most common cancer among women. Starting May 18, 2020, the HPV vaccine developed by Chinese researchers is available in provincial Maternity and Child Healthcare Hospital in Wuhan.
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. This HPV vaccine was pulled from the US market on 10/2016.
HPV Therapeutic Vaccines - Candidates
TG4001 - TG4001 is Transgene's vaccine candidate using an attenuated and modified poxvirus (MVA) as a vector expressing the HPV16 E6 and E7 proteins interleukin-2.
VGX-3100 - Inovio's investigational immunotherapy vaccine includes DNA plasmids targeting the E6 and E7 proteins of HPV types 16 and 18.
INO-3107 - Inovio's DNA medicine is evaluated in a Phase 1/2 trial to treat recurrent respiratory papillomatosis, a rare disease caused by human papillomavirus types 6 and 11 infections.
HPV Vaccine News
January 7, 2021 - The NEJM reported 'Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child.'
January 5, 2021 - Monique Luisi, an assistant professor at the University of Missouri School of Journalism, has studied more than 6,500 public HPV vaccine-related posts on Facebook from 2006 to 2016. In a previous study, Luisi used these Facebook posts to identify a negative trend on Facebook related to how people perceive the HPV vaccine. She suggests this negative trend on Facebook may also cause people to develop a false perception of the vaccine's health risk. After looking at the percentage of posts that made the vaccine seem more dangerous, less dangerous, or neither, Luisi found nearly 40% of Facebook posts about the HPV vaccine amplified a perceived risk. The data suggest these posts had momentum over time.
January 1, 2021 - American Academy of Pediatrics study: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.
December 12, 2020 - To address suboptimal HPV vaccination rates, this study applies an evidence-based community engagement strategy—BCT—in the private practice setting to engage patient stakeholders alongside private practice staff to develop messaging and interventions promoting the HPV vaccine. The BCT approach produces dissemination-ready interventions, incorporates both practice and community context, and improves the acceptability of evidence-based interventions to individual communities. This study will use a robust matched case-control evaluation to assess the implementation and effectiveness of the BCT approach to increase HPV vaccination rates among adolescents aged 9–17 years. While practices will not be randomized, clinics with similar demographics will be recruited to serve as matched controls. Ultimately, we anticipate this study will demonstrate the feasibility and effectiveness of using community-engaged strategies at the private clinic level to improve HPV vaccination rates and prevent HPV-related cancers.
December 11, 2020 - Royal College of Obstetricians and Gynaecologists - Insights from outside BJOG.
December 11, 2020 - In an article in JMIR Nursing, researchers explain how they applied user-centered design principles to develop a mobile health (mhealth) app to improve HPV vaccine uptake and how its use was evaluated with parents and parent-adolescent.
December 9, 2020 - INOVIO announced positive Phase 2 efficacy results demonstrating that DNA medicine VGX-3100, the company's lead immunotherapy asset, showed resolution of HPV-16/18-associated precancerous anal lesions in 50% (11 of 22) of subjects 6-months following the start of treatment. INOVIO plans to pursue a Phase 3 clinical trial for HPV-16-/18-associated anal dysplasia and apply rare and orphan disease designation for this indication in 2021.
December 7, 2020 - The interim data support proof of concept for HB-201 monotherapy as new immunotherapy for a difficult-to-treat patient population with multiple prior treatment failures. As of December 4, 2020, 22 patients have been enrolled in the first two cohorts, 15 were eligible for evaluation. Among the 15 evaluable patients, 11 patients had relapsed/refractory metastatic squamous cell head and neck cancer, all of whom had progressed on prior therapy with a PD1 inhibitor. As per RECIST1.1, in patients with third-line or later HNSCC, HB-201 demonstrated an unconfirmed response rate of 18% (one unconfirmed complete responder and one unconfirmed partial responder) and a 73% disease control rate (six stable disease patients, in addition to the two unconfirmed responses referenced above).
December 6, 2020 - A research team at the University of Saskatchewan and the Urban Public Health Network join forces for a project that seeks to eliminate cervical cancer. The project is being funded by the Canadian Partnership Against Cancer totaling $1.6 million. The goal is to eliminate cervical cancer in Canada by 2040.
December 1, 2020 - Researchers at the University of Tennessee Health Science Center and Emory University have received a major grant totaling $2.7 million from the National Cancer Institute/National Institutes of Health to conduct a five-year study to develop methods to improve adherence to the HPV vaccine. UTHSC will receive $1.25 million of the funding, with the remainder going to Emory and other universities collaborating on the project.
November 26, 2020 - The Lancet: WHO launched a global initiative to accelerate the elimination of cervical cancer and set up a historical milestone through the adoption of a resolution by 194 countries at the World Health Assembly that pledged, for the first time, to eliminate a malignant disease by pursuing three important steps: vaccination, screening, and treatment.
November 23, 2020 - PCI Biotech announced the successful Phase I proof of concept study for the fimaVacc technology accepted for publication in Frontiers in Immunology, a high impact immunology journal. The open-label Phase I study in more than 90 healthy volunteers was completed in 2019. The overall results provide proof-of-concept by demonstrating that fimaVacc enhances the immune responses to peptide and protein-based vaccines in healthy volunteers. The results further support fimaVacc’s potential to enhance the cellular immune responses that are especially important for vaccines' therapeutic effect. Moreover, the study shows that fimaVacc can be safely employed in humans.
November 17, 2020 - The WHO 'A cervical cancer-free future: First-ever global commitment to eliminate cancer.'
November 16, 2020 - AAP study: Cost-effectiveness of Interventions to Increase HPV Vaccine Uptake. Three interventions for increasing HPV vaccine coverage were cost-effective and offered substantial health benefits. Policymakers seeking to increase HPV vaccination should, at minimum, dedicate additional funding for QI visits, which are consistently effective at low cost and may additionally consider more resource-intensive interventions (reminder and recall or school-located vaccination).
November 16, 2020 - Study: 'We find 3 interventions for increasing HPV vaccination are cost-effective at common thresholds than the status quo. HPV vaccination interventions are a high-value state funding use and could prevent 3,000 to 14,000 incident HPV cancers over the next 50 years.
November 14, 2020 - College students from minority communities and communities of color are less likely to receive an HPV vaccine compared with individuals in the White community, with Black women significantly less likely than Black men to plan to receive the vaccination, according to results from a small study presented at the Association of Nurses in AIDS Care Virtual Conference.
November 3, 2020 - A new analysis published in the British Journal of Clinical Pharmacology shows that HPV vaccines are safe and well-tolerated in the male population. The side effects that may occur after immunization are similar in both sexes. "To the best of our knowledge, this is one of the first studies focused on the evaluation of the safety profile of HPV vaccines in males," the authors wrote.
October 29, 2020 - In an article in JMIR Nursing, researchers explain how they applied user-centered design principles to develop a mobile health (mhealth) app to improve HPV vaccine uptake and how its use was evaluated with parents and parent-adolescent dyads. The Vaccipack app is exclusively focused on adolescent vaccines and targets key parental beliefs related to HPV vaccines. The mhealth app is designed for parents to promote the initiation and completion of the HPV vaccine series in their adolescent children.
October 29, 2020 - Austra based HOOKIPA Pharma Inc. announced the first patient dosed with HB-202, a replicating arenavirus therapy based on the Pichinde Virus (PICV). HB-202 is part of a sequential alternating regimen of HB-202/HB-201 for treating Human Papillomavirus 16-positive (HPV16+) cancers in the ongoing HB-201 Phase 1/2 trial (NCT04180215).
October 27, 2020 - Transgene, a biotech company that designs and develops virus-based immunotherapeutics against cancer, announced the detailed results from the Phase 1b/2 trial combining TG4001 avelumab (BAVENCIO®), a human anti-PD-L1 antibody, in HPV16-positive recurrent and/or metastatic malignancies.
October 26, 2020 - A new study reported anal cancer is an uncommon but preventable disease, with 8,590 new cases projected (5,900 in women; 2,690 in men) and approximately 1,350 disease-related deaths (810 in women; 540 in men) for 2020. More than 90% of cases are linked with human papillomavirus (HPV).
October 26, 2020 - PDS Biotechnology Corporation announced that the Phase 2 clinical trial of PDS0101 combined with standard of care chemoradiotherapy to treat locally advanced cervical cancer. PDS0101 targets cancers associated with the human papillomavirus and combines the utility of the Versamune® platform with targeted antigens against HPV-expressing cancers.
October 19, 2020 - Transgene announced that detailed results of the data from the Phase 1b/2 trial combining TG4001, an HPV16 targeted therapeutic vaccine, with avelumab (BAVENCIO®), a human anti-PD-L1 antibody, in HPV16-positive recurrent and/or metastatic malignancies, will be presented in a poster presentation at the upcoming virtual meeting of the Society for Immunotherapy of Cancer taking place November 9-14, 2020.
October 12, 2020 - Canadian clinicians are warning that the cancellation of Ontario's in-school HPV vaccination programs in the spring of 2020 could lead to thousands of preventable cancers in the future if children aren't tracked to make sure they eventually get immunized. All Ontario children normally receive two doses of the vaccine in the fall and spring of Grade 7, but this spring's vaccinations were canceled due to the COVID-19 pandemic. That means last year's Grade 7 cohort missed its second dose, while parts of this fall's new batch of Grade 7 students could miss their first.
October 11, 2020 - South Korea Rep. Choi Hye-young proposed a revision bill of the Infectious Disease Control and Prevention Act. The amendment seeks to expand the national immunization program's scope to provide free HPV vaccines for not only 12-year-old females but both males and females aged under 18. Choi said: 'the government needs to expand the target of HPV vaccination to all children under 18, she emphasized.'
October 1, 2020 - Study: HPV Vaccination and the Risk of Invasive Cervical Cancer. HPV vaccination in women when young substantially reduces cervical cancer risk among Swedish girls and women 10 to 30 years old; quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years.
September 22, 2020 - In Bhutan, the prevalence of vaccine-targeted HPV types has decreased sharply, providing the first evidence of the effectiveness of a high-coverage national HPV vaccination program in a lower-middle-income country.
September 14, 2020 - Trends in Human Papillomavirus Vaccination in Commercially Insured Children in the USA.
August 27, 2020 - Health Canada has extended the indication for Gardasil 9 to include men between the ages of 27 and 45. Gardasil 9 was introduced in Canada in 2015 and has previously been approved for use in boys and men nine to 26 and girls and women from nine to 45 to prevent cervical, vulvar, vaginal, and anal cancers, along with lesions and genital warts.
August 21, 2020 - The CDC's National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — the United States, 2019. From 2018 to 2019, coverage with one or more doses of the HPV vaccine increased from 68.1% to 71.5%, whereas the percentage of adolescents who reported being up to date with their HPV vaccination series jumped from 51.1% to 54.2%. HPV vaccination coverage in the USA continues to improve for HPV, with some disparities among adolescents living at or above the poverty level. Those living outside a metropolitan statistical area had lower coverage with HPV.
August 12, 2020 - Study: HPV Vaccine May Reduce the Chance of Precancerous Condition.
August 4, 2020 - A new study in Denmark investigated the real‐life impact of quadrivalent HPV vaccination by comparing a cohort of women offered HPV vaccination with a cohort of women not offered HPV vaccination. The observed decrease in the detection of high‐grade cervical lesions following HPV vaccination is in line with results from the randomized trials and has important implications for future cervical screening of HPV vaccinated cohorts.
August 3, 2020 - The American Cancer Society's new guidance on human papillomavirus vaccination diverges from the U.S. CDC's recommendations. The CDC recommends shared clinical decision-making regarding human papillomavirus (HPV) vaccination in some adults aged 27-45 who are not adequately vaccinated. The ACS disagrees with the third recommendation for older adults.
July 30, 2020 - American Cancer Society published simplified guidelines saying most women should start molecular HPV testing at age 25, which is 4 years later than previous guidelines suggest.
July 29, 2020 - INOVIO announced that the U.S. Food and Drug Administration granted orphan drug designation for INO-3107, its DNA medicine being evaluated in a Phase 1/2 trial to treat recurrent respiratory papillomatosis (RRP). RRP is a rare disease caused by human papillomavirus types 6 and 11 infections. RRP causes noncancerous tumor growths leading to life-threatening airway obstructions and can progress to rare cases.
July 29, 2020 - The premature closure of Jamaica's schools in March because of coronavirus restrictions has resulted in thousands of girls missing out on the scheduled second dosage of the HPV vaccine. The Government has been offering to grade-seven girls since 2017 to prevent cervical cancer. More than 32,000 girls have been vaccinated so far under the school-based immunization program targeting girls ages 11-13 to safeguard against HPV, the second-leading cause of cancer-related mortality in Jamaica.
July 25, 2020 - Importance of lifetime sexual history on the prevalence of genital human papillomavirus among unvaccinated adults in NHANES: implications for adult HPV vaccination.
July 24, 2020 - Choosing the optimal HPV vaccine: The health impact and economic value of the nonavalent and bivalent HPV vaccines in 48 Gavi‐eligible countries.
July 16, 2020 - Study: Human papillomavirus and HPV vaccine knowledge, the intention to vaccinate, and HPV vaccination uptake among male college students. The cost of HPV vaccination and concerns about safety and side effects were the most frequently reported barriers to vaccination.
July 14, 2020 - Study: Estimating the direct effect of human papillomavirus vaccination on the lifetime risk of screen‐detected cervical precancer. Primary HPV testing combined with adjunct cytology at five‐year intervals still seems feasible even after nonavalent vaccination, although unlikely to be cost‐effective. Our results support a de‐intensification of screening programs in settings with high vaccination coverage.
July 6, 2020 - The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, the prevalence of HPV16, 31, and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infections in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may prevent around 82% of Japan's invasive cervical cancer cases. Concerning the preventive effect of histological abnormalities, we also reported a significant reduction in the incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the vaccine's efficacy has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and immediate action to be taken by the Japanese government.
June 9, 2020 - Clinical Review of GARDASIL 9 by the U.S. FDA.
June 4, 2020 - A research team at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center has found that the same vaccination programs target high-risk human papillomavirus (hrHPV) strains in the United States may not be as effective in protecting other populations of women from the disease.
June 3, 2020 - Vaccine manufacturers MSD, GSK, Innovax, Serum Institute of India Pvt. Ltd., and Walvax have pledged to ramp up HPV vaccine supply availability in Gavi-supported countries ahead of the Global Vaccine Summit 2020. This commitment is part of an ongoing UNICEF-led tender that aims to enable Gavi to dramatically increase its reach from 50 million girls, as initially planned, to 84 million girls during the next five-year period, leading to the prevention of an estimated 1.4 million future deaths from cervical cancer.
April 10. 2020 - More than a decade after vaccination, women who had received a single dose of HPV vaccine continued to be protected against cervical infection with the 2 cancer-causing HPV types targeted by the vaccine, HPV16 and 18. The new findings are from an extended follow-up of the NCI-sponsored Costa Rica HPV Vaccine Trial.
February 18, 2020 - The Use of Both Therapeutic and Prophylactic Vaccines in the Therapy of Papillomavirus Disease.
January 24, 2020 - The WHO published Human papillomavirus vaccines and infertility (from the meeting of 4-5 December 2019).
July 5, 2019 - A Dynamic Model of Vaccine Compliance: How Fake News Undermined the Danish HPV Vaccine Program.
HPV Vaccination Overview
The CDC recommends individuals should receive the full HPV vaccine series, regardless of the age group. The CDC recommends that 11- to 12-year-olds receive two doses of HPV vaccine at least six months apart, rather than the previously recommended three doses to protect against cancers caused by HPV infections.
Teens and young adults who start the series later, at ages 15 through 26 years, will continue to need three doses of HPV vaccine to protect against cancer-causing HPV infection. Young women can get the HPV vaccine through age 26, and young men can get vaccinated through age 21.
HPV vaccination is also recommended for men and women with compromised immune systems (including people living with HIV/AIDS) through age 26 if they did not get fully vaccinated when they were younger.
The U.S. FDA approved an expanded indication for GARDASIL9 to prevent oropharyngeal cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58 on June 13, 2020.
The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease.
HPV is a group of more than 150 related viruses. Each HPV virus in this large group is given a number, which is called its HPV type. HPV is named for warts (papillomas) some HPV types can cause.
Some other HPV types can lead to cancer, especially cervical cancer. There are more than 40 HPV types that can infect the genital areas of males and females. But some vaccines can prevent infection with the most common types of HPV.
HPV is transmitted through intimate skin-to-skin contact. You can get HPV by having vaginal, anal, or oral sex with someone who has the virus. It is most commonly spread during vaginal or anal sex.
HPV is the most common sexually transmitted infection (STI). Anyone sexually active can get HPV, even if you have had sex with only one person.
HPV is so common that nearly all sexually active men and women get it at some point in their lives. HPV can be passed even when an infected person has no signs or symptoms. You can develop symptoms years after you have sex with someone infected, making it hard to know when you first became infected.
In most cases, HPV goes away on its own and does not cause any health problems. But when HPV does not go away, it can cause health problems like genital warts and cancer, says the CDC.
Genital warts usually appear as small bumps or groups of bumps in the genital area. They can be small or large, raised or flat, or shaped like a cauliflower. A healthcare provider can usually diagnose warts by looking at the genital area.
Cervical cancer usually does not have symptoms until it is quite advanced, very serious, and hard to treat. For this reason, women need to get regular screening for cervical cancer. Screening tests can find early signs of disease so that problems can be treated early before they ever turn into cancer.
Other HPV-related cancers might not have signs or symptoms until they are advanced and hard to treat. These include cancers of the vulva, vagina, penis, anus, and oropharynx (cancers of the back of the throat, including the base of the tongue and tonsils).
Cancer often takes years, even decades, to develop after a person gets HPV. The types of HPV that can cause genital warts are not the same as the types of HPV that can cause cancers.
There is no way to know which people who have HPV will develop cancer or other health problems. People with weak immune systems (including individuals with HIV/AIDS) may be less able to fight off HPV and more likely to develop health problems.
There is no test to find out a person’s “HPV status.” Also, there is no approved HPV test to find HPV in the mouth or throat.
There are HPV tests that can be used to screen for cervical cancer. These tests are recommended for screening only in women aged 30 years and older. They are not recommended to screen men, adolescents, or women under the age of 30 years.
Most people with HPV do not know they are infected and never develop symptoms or health problems. Some people find out they have HPV when they get genital warts. Women may find out they have HPV when they get an abnormal Pap test result (during cervical cancer screening).
Others may only find out once they’ve developed more serious problems from HPV, such as cancers.
The American Cancer Society (ACS) published simplified guidelines on July 30, 2020, that state women with a cervix should start molecular HPV testing at age 25 -- 4 years later than previous guidelines suggest. According to the new recommendations, if primary HPV testing is not available, either a Pap test every 3 years or co-testing (i.e., combined cytology and HPV tests) every 5 years is acceptable.
Approximately 33,700 cancers are caused by HPV in the United States each year, including 12,900 oropharyngeal cancers among men and women, 10,800 cervical cancers among women, and 6,000 anal cancers among men and women; vaginal, vulvar, and penile cancers are less common.
HPV vaccination for adolescents has been routinely recommended for females since 2006 and for males since 2011, says the CDC.
The existing HPV vaccination program for adolescents has the potential to prevent the majority of these cancers. The mean age at acquisition of causal HPV infection for cancers is unknown but is estimated to be decades before cancer is diagnosed.
In 2017, coverage with ≥1 dose of HPV vaccine was 65.5% among adolescents aged 13 through 17. Although coverage with the recommended number of doses remains below the Healthy People 2020 target of 80% for adolescents, the U.S. HPV vaccination program has resulted in significant declines in the prevalence of vaccine-type HPV infections, anogenital warts, and cervical precancers.
For example, the prevalence of 4vHPV vaccine-type infection during 2013–2016, compared with those of the prevaccine era, declined from 11.5% to 1.8% among females aged 14 through 19 years and 18.5% 5.3% among females aged 20 through 24 years.
Also, declines have been observed among unvaccinated persons, suggesting protective herd effects, says the CDC.
CONTENT SOURCE: World Health Organization, US Centers for Disease Control and Prevention, FDA, research studies, manufacturer announcements, and the Precision Vax news network, which has been reviewed by healthcare providers, such as Dr. Bob Carlson.