Human Papilloma Virus Vaccine

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Continuing Education Activity

The 9-valent human papillomavirus (HPV) vaccine (9vHPV) is a vaccine used in the management and prevention of infection with human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52, 58. It is in the immunization class of medications. This activity reviews the indications, action, and contraindications for the 9-valent human papillomavirus (HPV) vaccine (9vHPV) as a valuable agent in the management and prevention of HPV infection and HPV-associated diseases. This activity will highlight the mechanism of action, adverse event profile, and other key factors of the 9-valent human papillomavirus (HPV) vaccine (9vHPV) administration pertinent for members of the healthcare team in the management of patients with HPV immunization.


  • Identify the mechanism of action and administration of the 9-valent human papillomavirus (HPV) vaccine (9vHPV).
  • Describe the adverse effects and contraindications of the 9-valent human papillomavirus (HPV) vaccine (9vHPV).
  • Explain the importance of appropriate monitoring for patients on the 9-valent human papillomavirus (HPV) vaccine (9vHPV).
  • Summarize some interprofessional team strategies for improving care coordination and communication to advance the 9-valent human papillomavirus (HPV) vaccine (9vHPV) immunization efforts.


The 9-valent human papillomavirus (HPV) vaccine (9vHPV) is a second-generation, non-infectious, recombinant, 9-valent vaccine indicated to prevent diseases and cancers caused by both low-risk and high-risk human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52, 58. HPVs are the number one sexually transmitted viruses causing precancerous and cancerous lesions. The 9-valent human papillomavirus (HPV) vaccine (9vHPV) has been licensed by the US Food and Drug Administration (FDA) since 2014, and it is the only HPV vaccine available in the United States that confers protection against specific HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

Three different FDA-approved vaccines protect against infection with a varying number of HPV types:

  • 2vHPV (bivalent vaccine): protects against HPV types 16 and 18 (not available in the US, but it is still in use in other countries)
  • 4vHPV (quadrivalent vaccine): protects against HPV types 6, 11, 16, and 18
  • 9vHPV (nine-valent vaccine): protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 

9vHPV is routinely recommended to both males and females from ages 9 to 45 years of age to help prevent the following diseases and dysplastic lesions caused by human papillomavirus:

  • Anal, oropharyngeal, cervical, vulvar, vaginal, and other head-and-neck cancers caused by HPV types 16, 18, 31,33, 45, 52, and 58
  • Condyloma acuminata (genital warts) caused by HPV types 6 and 11
  • Cervical adenocarcinoma in situ, anal, cervical, vulvar, vaginal intraepithelial neoplasias caused by HPV types 16, 18, 31,33, 45, 52, and 58

Routine vaccination with 9vHPV is a recommendation for:

  • Males and females from age 9 through 45 who have not previously received a vaccination or who did not complete the 3-dose regimen currently recommended
  • Gay, bisexual, and men who have sex with men (MSM) through age 26
  • Immunocompromised individuals who have no prior vaccination or who did not complete the 3-dose regimen
  • Victims of sexual abuse or assault
  • Transgender individuals

Mechanism of Action

The exact mechanism of action of 9vHPV is unknown since HPV only affects humans, which makes it challenging to study. Nevertheless, the belief is that the vaccine works by activating the humoral response. 9vHPV is synthetically manufactured from the oncogenic protein subunit component L1 virus-like particles (VLP) of the HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.[1][2] 

A 2016 immunogenicity study reports that the inactive HPV L1 VLPs in the vaccine produce neutralizing antibodies against HPV types eliciting a strong humoral immune response to protect against the diseases and dysplastic lesions caused by HPV.[3] The same study reported that antibody titers for 9vHPV are 10 to 100-fold greater than antibody titers produced by natural infection.[3] Thus, the efficacy of the vaccine appears to be mediated via humoral response mechanisms. 


9vHPV administration is an intramuscular (IM) injection in the deltoid region or anterolateral thigh area. A single dose for both adults and pediatric patients consists of a 0.5 mL suspension. 9vHPV is administered in a two- or three-dose schedule depending on patient age at initial vaccination.[4]

Two-dose schedule for ages 9 through 14 years at initial vaccination[4]:

  • 0, 6 to 12 months – a minimum of five months in between doses 
  • 0, 2, 6 months – if administration of the second suspension occurs before the 5-month mark, then a third suspension should be administered four months after the second dose, at the latest. 

Three-dose schedule for ages 15 through 45 years at initial vaccination[4]:

  • 0, 2, 6 months

It is important to know that if the schedule is interrupted, the series can continue as previously scheduled and do not need to be restarted.[5] Lastly, 9vHPV administration can take place at the same time as other routine vaccinations such as the meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap).[6] Coadministration of 9vHPV with either of these vaccinations is well tolerated and does not interfere with either effect; however, the recommendation is to administer in different body sites.[6]

Adverse Effects

The most common adverse effects recorded with 9vHPV are injection-site events, systemic events, and syncope.[7][8] Injection-site events were recorded within five days after vaccination and included: pain, swelling, erythema, and tenderness.[8][9] Systemic events were recorded within fifteen days after vaccination and included: headaches, pyrexia, fatigue, and nausea.[9] Also, syncope after administration of 9vHPV has been reported, occurring post administration of the vaccine and posing a significant risk of serious secondary injury to patients. 

A 2016 study concluded that incidences of adverse effects were comparable throughout all the age groups.[4] Additionally, this study also concluded that the safety profile of 9vHPV is comparable to its quadrivalent counterpart, 4vHPV. Injection site effects were more common with 9vHPV given a greater amount of HPV virus-like antigens and aluminum hydroxyphosphate sulfate adjuvants, which help potentiate the immunological response.[4][10]


Vaccine-related anaphylactic reactions are uncommon; however, anaphylaxis to a known ingredient of any vaccine is an absolute contraindication to immunization.[7]

As a result, 9vHPV is contraindicated in individuals with a history of hypersensitivity reactions to yeast since 9vHPV is a recombinant vaccine expressed in Saccharomyces cerevisiae (brewer’s yeast). Contraindications also include persons who have had hypersensitivity reactions to a previous dose of 9vHPV or 4vHPV (quadrivalent vaccine).[5]

The safety of 9vHPV has not been a topic of study in pregnant human subjects; thus, 9vHPV is not currently recommended in pregnancy. A 2018 animal study assessed the general, reproductive, and developmental toxicity of 9vHPV in Sprague-Dawley rats. The study followed a 3-month repeat-dose toxicity study on rats reporting no effects on the reproductive ability of rats, no effects on offspring development, no vaccine-related fetal abnormalities, and no effect on male rat fertility.[11] 

These results add to the available data that 9vHPV does not increase the risk of adverse pregnancy outcomes in rats; however, more studies need to evaluate the safety profile in pregnant human subjects. Currently, standard protocol dictates that if a woman is found to be pregnant, the vaccination series should be halted and resumed after pregnancy.[12]


Patients should have monitoring for acute onset of signs and symptoms of anaphylactic reactions such as hypotension, tachycardia, urticaria, and respiratory compromise. Health care providers should have access to immediate treatment, such as epinephrine autoinjectors. 

Also, patients should receive monitoring for occurrences of syncope to prevent serious secondary injury to the patient. Health care professionals should monitor patients for presyncope signs and symptoms for 15 minutes when administering 9vHPV. Additionally, standard operating procedures should in place to avoid serious secondary injuries that could result from the collapse of the patient, such as having the patient sit down and have the healthcare professional stay near the patient in case the patient sways or collapses.  


9vHPV is a generally well-tolerated vaccine that has a high safety profile with the most common side effects being due to minor issues such as injection-site pain, swelling, erythema, and tenderness.[9][8] Minor systemic effects have also been reported, such as headaches, pyrexia, fatigue, and nausea.[9]

More dangerous toxic effects are attributable to anaphylaxis and hypersensitivity reactions. In the case of an anaphylactic reaction, health care providers should be ready to immediately administer 1.0 mg/mL of epinephrine, intramuscularly (IM) in the anterolateral vastus lateralis muscle. Administration of IM epinephrine should be repeated every 5 to 15 minutes until achieving the desired response.[13]

Enhancing Healthcare Team Outcomes

To support widespread vaccination efforts and increase global prevention of diseases and dysplastic lesions caused by human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52, and 58, clinicians must increase patient awareness during wellness visits on the importance of obtaining HPV vaccination. Physicians should also educate their patients on the different cancers and precancerous lesions that are avoidable when immunized with 9vHPV. Also, it is imperative to urge patients to complete the recommended three-dose sequence of 9vHPV. One way in which physicians can increase vaccine completion rates is in-person scheduling of the next follow-up visits. 

Furthermore, to increase patient safety and avoid syncope-related injuries, patients should be monitored by healthcare professionals for 15 minutes when administering 9vHPV. Further, clinics, pharmacies, and hospitals should have implemented standard operating procedures to avoid serious injury, such as having a safe space for vaccine administration.

Moreover, healthcare professionals should be aware of and be alert to the acute onset of symptoms of an anaphylactic reaction. All healthcare team members should receive training in the administration of epinephrine auto-injectors. Implementation of these interprofessional strategies can help achieve better outcomes with fewer adverse reactions while increasing vaccine-completion rates and increasing public awareness of the importance of HPV vaccination with 9vHPV.

Article Details

Article Author

Lucia Soca Gallego

Article Author

Alvio Dominguez

Article Editor:

Mayur Parmar


9/14/2021 8:48:24 PM



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