This is one of the more controversial #vaccines, up with the MMR vaccine and now COVID-19. The data here and the conversation really, varies widely. All of this we discuss in the vaccine forum offered active members of Eden Family Practice. What I'd like to offer here is more basic informational material, and maybe, additional points to think upon.
As most of you probably know, the HPV vaccine is for the human #papillomavirus (HPV) which is a virus which is transmitted sexually or by contact with mucosal surfaces. It is the most commonly transmitted sexual infection in the United States. Many are without symptoms or symptoms are transient, so show up quickly and disappear. This virus can lead to warts on the vulva or even in the vagina, and often around the anus. The HPV virus can also lead to cancer, but typically those which do lead to cancer do not also present themselves with #warts.
There are approximately eight different types of nonmucosal or cutaneous wart viruses, which are often found on the hands and feet. Another forty types are specific to mucosal areas, including the genital area. Among these, viruses can be lower risk for cancer, or higher risk. The lower risk types include: HPV-6, HPV-11, and others, which again, are often on the genitals, including a woman's cervix, and can also be found in the oral cavity, including the larynx. The high risk variety includes HPV-16, HPV-18, and others. HPV-16 is responsible for half of cervical cancers and the HPV-16 and HPV-18 together account for 70 percent of cervical cancers. These are the #cancer precursors, and even your anogenital cancers. While the low risk HPV types can cause low-grade cervical abnormalities and therefore, pap smear changes, it is these higher risk types which cause your high-grade cervical changes that are evident on the pap smear.
Annual number of new HPV infections are about 14 million each year, per the CDC. About 79 million adults are infected which means that more than 80 percent of the population will face HPV #infection at some point in their life. As I mentioned, some of these infections are transient, so they present and resolve fairly quickly. One may not ever know they were even infected. Others have a more persistent infection and these are the ones who have genital warts which hang around a little longer or who ultimately suffer cancer.
These warts are found on the cervix, anus, vagina, vulva, penis, or even in the mouth. A few years ago I had a woman present with a rather large mass in the back of her throat which was later diagnosed as a HPV wart. There are legends of midwives having performed resuscitation to neonates, without using a mouthpiece, who later suffered HPV infections in their mouths. Most HPV infections are without symptoms and do not cause disease, but some can also cause recurrent respiratory papillomatosis and even cancer.
In 2015, oropharyngeal cancer surpassed cervical cancer as the most common HPV-associated cancer. Read that again! Yes, cancer in the mouth and airway has now surpassed cancers associated with the #cervix as a result of the sexually transmitted wart virus! Astounding, huh? Cervical cancer remains the most prevalent HPV-associated cancer in women; however, the number of new HPV-associated cancers each year include 13,500 new cases of oropharyngeal which is five times more common in men. New cases of cervical HPV is discovered in about 10,900 women each year, with anal findings at 6,200 each year, vulvar and vaginal cases at 3,400 and penile HPV-cases at about 800 each year. This is the reason men have gained more attention, as a target audience, for the HPV vaccine.
HPV Vaccine Development
The very first vaccine was available in the United States in 2006, #Gardasil. It addressed HPV-6, HPV-11, HPV-16, and HPV-18, and was recommended for females aged 9 years to 26-years. A few years later, in 2009, Cervarix was introduced and it was specific to HPV-16 and HPV-18 for females aged ten years to 25-years. Gardasil 9 was approved by the FDA in 2014, and it covers nine different strains of HPV (6, 11, 16, 18, 31, 33, 45, 52, and 58). It is offered to both males and females 9 years through 45 years. Currently the Gardasil-9 is the only HPV vaccine available in the United States.
Taken together, more than 70K men and women were enrolled in HPV vaccine clinical trials before licensure. After they completed the full vaccine series, 98 percent of these patients developed an HPV antibody response. In randomized controlled trials, 9vHPV vaccination protected against HPV infection in 95 to 99 percent of patients and high-grade cervical, #vulvar, and vaginal neoplasia in 97 to 100 percent of patients.
Safety of 9vHPV
Most all adverse events reported are mild or moderate injection-site reactions, including pain, swelling or redness at the site of injection. The 9vHPV has shown to have even more of these local complaints with the injection. When we look across all seven phases of the three trials conducted, including more than 15K people who received the 9vHPV vaccine, series adverse reactions were quite rare, at less than 0.1 percent. Syncope can occur, so fall prevention is advised. Post-licensure data from the Vaccine Adverse Event Reporting System (VAERS) have confirmed findings from randomized controlled trials.
What many have claimed concern about, regarding the HPV vaccine, is an association with #autoimmune disease. There are case study reports suggesting post-vaccine development of autoimmune and demyelinating disease which have been discussed widely on social media and other news sites. Studies of large nationwide registers have not shown the same, or a correlation between vaccination and multiple sclerosis.
In 2009, concerns were raised about higher rates of venous thromboembolism (VTE) following vaccination with the 4vHPV. This includes both deep vein thrombosis and pulmonary embolism. Studies have found however, that when adjusting for oral contraceptive use, the vaccine does not seem associated with these adverse events (Scheller, 2014; Shimabukuro, 2019; & Slade, 2009).
Current Vaccine Recommendations for HPV
Both boys and girls are recommended routine vaccination for the HPV vaccine between the ages of 11 and 12 years, but this can be offered as young as age 9 years. The goal of course, is to offer this prior to exposure to HPV through sexual activity (Meites, 2019).
Certainly this vaccine is also recommended to anyone over the age of twelve who for whatever reason did not get the HPV vaccine previously. Shared decision-making is offered to those older than 27 years, through 45-years-of-age, particularly those at high risk for HPV-related disease. Typically, these are considered those who are transgendered, men having sex with men, immunocompromised, or have multiple risks such as smokers, heavy alcohol use, or obesity (Meites, 2019).
HPV vaccination should be delayed until after pregnancy, although it is not recommended that the clinician confirm the absence of pregnancy prior to administration via laboratory testing. Studies have demonstrated that outcomes of those who have received vaccination during pregnancy are comparable to those who were not #pregnant.
When a client has already been infected with HPV, obtaining the vaccine may prevent future infection with another of the many varieties of wart viruses; therefore, the vaccine is recommended regardless of the presence of HPV infection, HPV-associated precancer lesions, or anogenital warts. Severity of lesions may negatively correlate with effectiveness of HPV vaccination. Clients should understand that HPV vaccination will not benefit existing HPV infections, lesions, cancer, or warts.
When a client is immunocompromised, they should receive a three dose series up through about the age of 26 years. Vaccination may result in a lower titer for these people, but the risk for HPV-related cancers is also higher for them so vaccination can be important on these grounds. The theory is that while they may have less benefit, they would have no protection without vaccination.
When males and females receive the HPV vaccine prior to their 15th birthday, the are only recommended two doses, spaced six to twelve months apart. The third dose would not be necessary. However, once they reach 15 years, they should receive the second dose within one to two months, and then a third dose six months later. Those who are immunocompromised are also recommended three doses, on the same schedule. If dosing is interrupted, the series does not need to be restarted. Minimum dosing intervals are dependent on the age of when that first vaccine was administered.
If an individual was started on the older 2vHPV or 4vHPV, then their series can be completed with the newer 9vHPV using the minimum interval schedule and if one has completed the series with either of these vaccines, the 9vHPV vaccine is not currently recommended for them. There haven't been any safety concerns in utilizing the 9vHPV following the prior two options.
Efficacy for Preventing HPV-Related Diseases
What is understood today, is that the HPV vaccine has decreased the incidence of anogenital warts and cervical cancer precursors. Longitudinal studies evaluating the effects of vaccination on cancers is still ongoing. The CDC estimates that 92 percent of the 34,800 cancers caused by HPV could be prevented by vaccine.
HPV vaccine protection appears to persist for up to ten years with no loss of effectiveness. This depends on the type of virus evaluated and the age of the individual when administered. This is an important consideration when choosing when to administer, as giving this vaccine to a child who is nine years old means, at best, they are protected until the age of 19 years, but currently there is no recommendation to offer a second series after this timeline. Now in my forties, I am thinking about those coming out of long-term relationships where maybe they were #monogamous, but following divorce in their later decades, exposure to sexually transmitted disease has increased, and whether vaccinated previously or not, they would be outside this ten year window if administration occurred per routine.
An Australian research study evaluating the effectiveness of the HPV vaccine program determined that coupled with HPV-based cervical screening programs, HPV vaccination is expected to decrease the Australian rate of cervical cancer to less than one case per 100,000 women by year 2066. Population-wide decreases in #CIN have been reported in the United States as well.
Low Vaccine Coverage in the United States
Vaccine coverage in the United States is increasing, but still considered suboptimal by professional groups, including the CDC. Recent increases has generally reflected an increasing incidence of vaccination administration among #boys. HPV vaccination rates are still well below the 80 percent target for 2020. There are often delays in vaccination and missed doses.
Among girls aged 13 years, 23 percent have not received the full series, and among girls who are 17 years, 13 percent have not received the full schedule. The risk for cervical HPV infection increased significantly in older adolescents who took more than one year to complete HPV vaccination verses those who took less than one year.
When parents have considered the possible benefits and risks associated with this vaccine, or any vaccine, and are considering a discussion with their teenage child regarding vaccination administration, it is important to educate them about the information available. Certainly they are interested in matters that effect them and will have their own ideals and values to contribute to this decision making. Hesitancy is common regarding vaccines, and certainly many don't want to endure the pain that comes with injections. There may be misconceptions about this vaccine and sexual activity or the necessity of boys needing this particular vaccine. One of the more common concerns I hear from my own clients, is that they worry about the combination or exposing their child to multiple vaccinations. These discussions are explored a bit more thoroughly within our member's group.
Attia, A. C. et al. (2018). Ann Med, 50(3), 209-225.
Markowitz, L. E. et al. (2014). MMWR Recomm Rep, 63(RR-05),1-30.
Meites, E., et al. (2019). MMWR Morb Mortal Wkly Rep, 68(32), 698-702.
Scheller, N. M. et al. (2014). JAMA, 312(2), 187-188.
Shimabukuro, T. T. et al. (2019). Pediatrics, 144(6), e20191791.
Slade, B. A., et al. (2009). JAMA, 302(7), 750-757.