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Human Papillomavirus Vaccine

Class: Vaccines
ATC Class: J07BF01
VA Class: IM100
Brands: Gardasil 9

Medically reviewed by Drugs.com. Last updated on Nov 18, 2019.

Introduction

Inactivated (recombinant) virus vaccine.1 166 201 202 Contains virus-like particles (VLPs) of the major capsid (L1) proteins of certain human papillomavirus (HPV) types;1 166 201 202 used to stimulated active immunity to the HPV serotypes represented in the vaccine.1 166 201 202 Commercially available in US as human papillomavirus 9-valent vaccine recombinant (9vHPV) containing VLPs of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.1 Other HPV vaccines (human papillomavirus quadrivalent vaccine [4vHPV], human papillomavirus bivalent vaccine [2vHPV]) no longer available in US.207

Uses for Human Papillomavirus Vaccine

Prevention of Disease Caused by HPV

Prevention of cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58 in females 9 through 45 years of age.1 Also prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, including cervical intraepithelial neoplasia (CIN) grades 1 and 2/3, cervical adenocarcinoma in situ (AIS), vulvar intraepithelial neoplasia (VIN) grades 2 and 3, vaginal intraepithelial neoplasia (VaIN) grades 2 and 3, and anal intraepithelial neoplasia (AIN) grades 1, 2, and 3, in females 9 through 45 years of age.1

Prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58 and prevention of precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, including AIN grades 1, 2, and 3, in males 9 through 45 years of age.1

Prevention of genital warts (condyloma acuminata) caused by HPV types 6 and 11 in females and males 9 through 45 years of age.1

Anogenital HPV is the most common sexually transmitted infection in US;166 201 approximately 79 million individuals already infected and 14 million more become infected each year (about 50% of cases are occurring in adolescents and young adults 15 through 24 years of age).166 201 344 Most HPV infections are asymptomatic and resolve spontaneously within 1–2 years, but some low-risk (nononcogenic) HPV types cause anogenital warts (condyloma acuminata) and some high-risk (oncogenic) HPV types are associated with persistent anogenital infections, dysplastic lesions, and development of cervical and other anogenital cancers (e.g., penile, vulvar, vaginal, anal).105 166 201 344 High-risk HPV types 16 and 18 cause about 70% of all cases of cervical and anogenital cancer in females and about 70% of all cases of anal cancer in males.105 166 201 344

The 9-valent HPV vaccine (9vHPV) provides protection against disease caused by high-risk (oncogenic) HPV types 16, 18, 31, 33, 45, 52, and 58;1 201 202 203 also provides protection against disease caused by low-risk (nononcogenic) HPV types 6 and 11.1 201 202

The CDC Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend that all females and males 9 through 26 years of age receive routine and catch-up vaccination with 9vHPV.199 200 202 207 212

ACIP states that routine and catch-up vaccination with 9vHPV recommended for females and males 9 through 26 years of age with primary or secondary immunocompromising conditions that might reduce cell-mediated or humoral immunity (e.g., B-lymphocyte antibody deficiencies, T-lymphocyte complete or partial defects, HIV infection, malignant neoplasms, transplantation, autoimmune disease, immunosuppressive therapy).207

ACIP states make decisions regarding use of 9vHPV in females and males 27 through 45 years of age based on shared decision-making and discussion between patient and clinician regarding benefits and risks of the vaccine.212

First dose of HPV vaccine usually given at 11 through 12 years of age, but may be given to those as young as 9 years of age.28 105 199 201 207 ACIP and other experts recommend routine HPV vaccination in individuals as young as 9 years of age when sexual abuse or sexual assault is suspected.105 199 207

Ideally, complete HPV vaccination before potential exposure to HPV occurs through sexual activity; however, 9vHPV may still be given to age-appropriate individuals who are sexually active and may have already been exposed to HPV.28 105 155 156 166 201 Although sexually active individuals who have not been infected with any HPV types contained in the vaccine receive the full benefit of vaccination, vaccination may still be beneficial for those who have already been infected with ≥1 of the vaccine HPV types.19 155 166 201

9vHPV can be used to continue or complete HPV vaccination series in individuals who previously received 1 or more doses of HPV vaccine no longer available in US (4vHPV, 2vHPV).207 ACIP states that individuals who initiated HPV vaccination prior to 15 years of age and received 2 or 3 doses of any HPV vaccine administered at recommended dosage schedule are considered adequately vaccinated.207 Individuals who initiated HPV vaccination at ≥15 years of age and received 3 doses of any HPV vaccine administered at recommended dosage schedule also considered adequately vaccinated.207 ACIP has made no recommendations to date regarding additional vaccination with 9vHPV in individuals considered adequately vaccinated with 4vHPV or 2vHPV.207

Prevaccination HPV testing or screening (e.g., Papanicolaou [Pap] testing or screening for high-risk HPV DNA, type-specific HPV DNA tests, HPV antibody test) not needed and not recommended.28 166 201 344 HPV vaccine can be used regardless of history of anogenital warts, abnormal Pap or HPV tests, or anogenital precancer.166 344

Does not prevent infection or disease caused by HPV types not represented in the vaccine.1 12 105 201 204

Does not provide protection against disease from vaccine and nonvaccine HPV types to which an individual has previously been exposed through sexual activity.1 201

Not used for treatment of active genital warts and not used for treatment of precancerous or dysplastic lesions (e.g., AIN, CIN, VIN, VaIN) or cervical, vulvar, vaginal, or anal cancer.1 105

Human Papillomavirus Vaccine Dosage and Administration

Administration

Administer by IM injection.1

Do not administer IV, sub-Q, or intradermally.1

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;1 134 may be accompanied by transient neurologic signs (e.g., tonic-clonic limb movements).1 134 Occurs most frequently in adolescents and young adults.134 Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope.134 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134 If syncope occurs, observe patient until symptoms resolve.134 (See Syncope under Cautions.)

May be given concurrently with other age-appropriate vaccines.105 134 166 199 200 201 (See Interactions.) When multiple vaccines administered during a single health-care visit, give each parenteral vaccine using separate syringes and different anatomic sites.134 Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134

IM Administration

Administer IM in deltoid region of upper arm or anterolateral aspect of upper thigh.1

To ensure delivery of vaccine into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.134

Shake well immediately prior to administration to provide a uniform, white, cloudy suspension.1 Discard if vaccine contains particulates, appears discolored, or cannot be resuspended with thorough agitation.1

Do not dilute;1 do not mix with any other vaccine or solution.1

Dosage

Dosage schedule (i.e., number of doses) for 9vHPV is based on age at the time first dose is administered and the immunocompetence of vaccinee.199 200 207

Manufacturer recommends a 2- or 3-dose series if HPV vaccination initiated at 9 through 14 years of age and a 3-dose series if initiated at 15 through 45 years of age.1 ACIP, AAP, and other experts recommend a 2-dose series if initiated at 9 through 14 years of age and a 3-dose series if initiated at 15 through 45 years of age;199 200 207 these experts recommend a 3-dose series in all immunocompromised individuals ≥9 years of age.199 200 207

If interruptions occur resulting in an interval between doses longer than recommended, there is no need to start the vaccination series over.105 166 201 207

Do not use an accelerated schedule (i.e., using intervals between doses shorter than recommended).105 166 207

Pediatric Patients

Prevention of Disease Caused by HPV
Females and Males 9 through 14 Years of Age
IM

Each dose is 0.5 mL.1

If 2-dose regimen used, manufacturer states give second dose 6–12 months after first dose (i.e., 0 and 6–12 months);1 if second dose given <5 months after first dose, give a third dose ≥4 months after second dose.1 If 3-dose regimen used, manufacturer states give second dose 2 months after first dose and give third dose 6 months after first dose (i.e., 0, 2 and 6 months).1

Routine or catch-up vaccination (immunocompetent): ACIP, AAP, and others recommend 2-dose regimen.199 207 Give first dose at 11 through 12 years of age (may be given as early as 9 years of age) and give second dose 6–12 months after first dose (i.e., 0 and 6–12 months).199 207 Minimum interval between first and second doses is 5 months;199 207 if second dose given <5 months after first dose, give third dose ≥12 weeks after second dose and ≥5 months after first dose.199 207

Routine or catch-up vaccination (immunocompromised): ACIP, AAP, and others recommend 3-dose regimen.199 207 Give second dose 1–2 months after first dose and give third dose 6 months after first dose (i.e., 0, 1–2, and 6 months).199 207 Minimum interval between first and second doses is 4 weeks;207 minimum intervals for third dose are 12 weeks after second dose and 5 months after first dose.207

Previously received ≥1 dose of 4vHPV or 2vHPV (no longer available in US): Vaccination series may be continued or completed with 9vHPV.207 ACIP states that individuals are considered adequately vaccinated if HPV series was initiated prior to 15 years of age and 2- or 3-dose regimen of any vaccine (9vHPV, 4vHPV, or 2vHPV) was given using recommended dosage schedules.207

Females and Males 15 through 18 Years of Age
IM

Each dose is 0.5 mL.1

Routine or catch-up vaccination (immunocompetent or immunocompromised): Manufacturer, ACIP, AAP, and others recommend 3-dose regimen.1 199 207 Give second dose 1–2 months after first dose and give third dose 6 months after first dose (i.e., 0, 1–2, and 6 months).1 199 207 Minimum interval between first and second doses is 4 weeks;199 207 minimum intervals for third dose are 12 weeks after second dose and 5 months after first dose.199 207

Previously received ≥1 dose of 4vHPV or 2vHPV (no longer available in US): Vaccination series may be continued or completed with 9vHPV.207 ACIP states that individuals are considered adequately vaccinated if HPV series was initiated at ≥15 years of age and a 3-dose regimen of any vaccine (9vHPV, 4vHPV, or 2vHPV) was given using recommended dosage schedules.207

Adults

Prevention of Disease Caused by HPV
Females and Males 19 through 45 Years of Age
IM

Each dose is 0.5 mL.1

Routine or catch-up vaccination (immunocompetent or immunocompromised): 3-dose regimen recommended.1 155 200 Give second dose 1–2 months after first dose and give third dose 6 months after first dose (i.e., 0, 1–2, and 6 months).1 200 207 Minimum interval between first and second doses is 4 weeks;200 207 minimum intervals for third dose are 12 weeks after second dose and 5 months after first dose.200 207

Previously received ≥1 dose of 4vHPV or 2vHPV (no longer available in US): Vaccination series may be continued or completed with 9vHPV.207 ACIP states that individuals are considered adequately vaccinated if HPV series was initiated at ≥15 years of age and 3-dose regimen of any vaccine (9vHPV, 4vHPV, or 2vHPV) was given using recommended dosage schedules.207

Special Populations

Hepatic Impairment

No specific dosage recommendations.1

Renal Impairment

No specific dosage recommendations.1

Geriatric Patients

Safety and efficacy not established in females or males ≥65 years of age.1

Cautions for Human Papillomavirus Vaccine

Contraindications

  • Hypersensitivity to any vaccine component (including severe allergic reactions to yeast).1 Hypersensitivity to a previous dose of HPV vaccine.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylactic/anaphylactoid reactions, bronchospasm, urticaria, angioedema, generalized rash, erythema multiforme) reported with HPV vaccine.1 29 35 36

Most reported cases of anaphylaxis occurred following first dose in the HPV vaccination series.36 In an Australian vaccination program in adolescents and women 12–26 years of age, rate of anaphylaxis following HPV vaccination was 2.6 cases per 100,000 doses.36

Cause of hypersensitivity reactions following administration of HPV vaccine unclear.35 36 When sensitivity tests were performed in individuals who had suspected anaphylaxis following a dose of HPV vaccine, skin prick or intradermal tests using the vaccine, yeast, or polysorbate 80 generally were negative.29 35 However, at least one patient had a positive intradermal test that was consistent with IgE-mediated hypersensitivity.35

Appropriate medical treatment and supervision must be available in case an anaphylactic reaction occurs following the administration of the vaccine.1

Yeast Allergy

9vHPV is manufactured using fermentation cultures of a recombinant strain of Saccharomyces cerevisiae (yeast);1 each dose contains <7 mcg of yeast protein.1

Data from the Vaccine Adverse Event Reporting System (VAERS) indicate that recombinant yeast-derived vaccines pose a minimal risk for anaphylactic reactions in individuals with a history of allergic reactions to yeast.23

Syncope

Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity reported following vaccination with HPV vaccine.1 Tonic-clonic movements are transient and typically respond to restoration of cerebral perfusion by maintaining vaccinee in a supine or Trendelenburg position.1

Syncope also reported with other vaccines; occurs most frequently in adolescents and young adults.134

Observe vaccinee for 15 minutes following vaccination;1 134 have procedures in place to avoid falling injury and restore cerebral perfusion if syncope occurs.1 134 (See Administration under Dosage and Administration.)

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as a result of disease (e.g., congenital immunodeficiency, HIV infection, hematologic or generalized malignancy, solid organ transplantation) or immunosuppressive therapy.105 135 155 156 200 207 Consider possibility that the immune response to the vaccine and efficacy may be reduced in these individuals.1 105 135 155 156 166 200 201 207 Immunosuppressed individuals should receive a 3-dose HPV vaccination series.207 (See Dosage under Dosage and Administration.)

Although data not available regarding safety, efficacy, and immunogenicity in individuals with HIV infection, ACIP, AAP, and others state that recommendations regarding use of HPV vaccine in HIV-infected individuals are the same as those for individuals who are not infected with HIV.135 155 156 199 200 However, HIV-infected individuals 9 through 26 years of age should receive a 3-dose HPV vaccination series.155 156 199 200 207

Generally, administer prior to initiation of immunosuppressive therapy or defer until immunosuppressive therapy discontinued.105 134 (See Immunosuppressive Agents under Interactions.)

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent acute illness on severity of symptoms and etiology of the illness.134

ACIP states mild acute illness does not preclude vaccination.134

ACIP states moderate or severe acute illness (with or without fever) is a precaution for vaccination;134 defer vaccines until individual has recovered from the acute phase of the illness.134 This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.134

Individuals with Bleeding Disorders

Advise individuals who have bleeding disorders or are receiving anticoagulant therapy and/or their family about risk of hematoma from IM injections.134

ACIP states that vaccines may be given IM to such individuals if a clinician familiar with the patient’s bleeding risk determines that the vaccine can be administered with reasonable safety.134 In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.134 In individuals receiving therapy for hemophilia, IM vaccines can be scheduled for administration shortly after a dose of such therapy.134

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against HPV infection.1

Vaccination with HPV vaccine does not substitute for routine cervical cancer screening.1 19 Female recipients should continue to undergo cervical cancer screening (e.g., Pap tests) according to current recommendations for such testing.1 105 166 201 202 344

Male and female recipients of HPV vaccine should continue anal cancer screening if recommended by health-care professional.1

HPV vaccine does not provide protection against disease due to HPV types not contained in the vaccine and does not provide protection from vaccine and non-vaccine HPV types an individual previously has been exposed to through sexual activity.1

Although the vaccine will not provide any beneficial effects in regard to preexisting HPV infections, it will provide protection against the vaccine HPV types that the vaccinee has not already acquired.19

Not used for treatment of active genital warts.1

Not used for treatment of precancerous or dysplastic lesions (e.g., AIN, CIN, VIN, VaIN) and not used for treatment of cervical, vulvar, vaginal, or anal cancer.1

Duration of Immunity

Duration of immunity following 2- or 3-dose vaccination series of HPV vaccine not determined.1 207

Data to date suggest that a 3-dose regimen of HPV vaccine induces anti-HPV antibody levels that provide protection against HPV types represented in the vaccine for at least 10 years.207 Similar duration of protection is expected when a 2-dose regimen of HPV vaccine used.207

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.134

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.134 (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.134

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.134

Specific Populations

Pregnancy

No adequate and well-controlled studies using 9vHPV in pregnant women.1 Manufacturer states that human data to date have not demonstrated any vaccine-associated risk of major birth defects and miscarriages when 9vHPV administered during pregnancy.1

ACIP, AAP, ACOG, and others state HPV vaccine not recommended for use in pregnant women.28 105 134 155 166 200 201 202 207 212

Although pregnancy testing not needed before initiation of HPV vaccine series,105 166 200 201 202 207 212 question sexually active individuals about the possibility of pregnancy.105 Delay HPV vaccination until pregnancy completed.166 200 212 If a woman is found to be pregnant after HPV vaccine series initiated, ACIP, AAP, ACOG, and others state no intervention needed but defer any remaining doses until after completion of the pregnancy.28 105 166 200 201 202 207

Report any exposure to 9vHPV vaccine that occurs around the time of conception or during pregnancy to the pregnancy registry at 800-986-8999.1

Lactation

Data insufficient to assess the effects of 9vHPV on breast-fed infant or on milk production/excretion.1

Manufacturer states consider benefits of breast-feeding and the importance of 9vHPV to the woman;1 also consider potential adverse effects on breast-fed child from the vaccine or from the underlying maternal condition (i.e., susceptibility to HPV infection).1

ACIP states that inactivated vaccines do not pose any unusual risks for the mother or her breast-fed infant.134 These and other experts state HPV vaccine may be used in women who are breast-feeding.28 105 166 201 212

Pediatric Use

Safety and efficacy not established in females or males <9 years of age.1

Adults 27 through 64 Years of Age

Safety of 9vHPV in adults 27 through 45 years of age inferred from safety data for 4vHPV (no longer available in US) in individuals 9 through 45 years of age and safety of 9vHPV in individuals 9 through 26 years of age.1

Safety and efficacy not established in females or males ≥46 years of age.1

Geriatric Use

Safety and efficacy not established in females or males ≥65 years of age.1

Common Adverse Effects

Females 9 through 26 years of age: Injection site reactions (pain, swelling, erythema, pruritus, hematoma), headache, fever, nausea, dizziness, fatigue, oropharyngeal pain.1

Males 9 through 26 years of age: Injection site reactions (pain, swelling, erythema, hematoma), headache, fever, nausea, dizziness, fatigue.1

Interactions for Human Papillomavirus Vaccine

Immunosuppressive Agents

Immune responses to vaccines, including HPV vaccine, may be reduced in individuals receiving immunosuppressive agents.1 105 134 135

Generally, give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive therapy and, because of possible suboptimal response, do not give during immunosuppressive therapy and for certain periods of time after such therapy discontinued.105 134 135 (See Specific Drugs under Interactions.)

Time to restoration of immune competence varies depending on type and intensity of immunosuppressive therapy, underlying disease, and other factors;105 optimal timing for vaccine administration after discontinuance of immunosuppressive therapy not identified for every situation.105

Vaccines

Although specific studies may not be available evaluating concurrent administration with each antigen, simultaneous administration of HPV vaccine with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations.105 134

Immunization against HPV can be integrated with immunization against diphtheria, tetanus, pertussis, hepatitis B, influenza, meningococcal disease, pneumococcal disease, poliovirus, measles, mumps, rubella, and varicella.105 134 Give each parenteral vaccine using separate syringes and different injection sites.134

Specific Drugs

Drug

Interaction

Comments

Estrogens/progestins

No evidence to date that hormonal contraceptives alter immunologic response to HPV vaccine1

Hepatitis B (HepB) vaccine

Concurrent administration of 3-dose vaccination series of 4vHPV (no longer available in US) and HepB vaccine (Recombivax HB) (at different injection sites) during same health-care visits in women 16–24 years of age did not decrease antibody response to either vaccine and did not increase incidence of clinically important adverse effects compared with administration during separate visits25

May be administered concurrently (using different syringes and different injection sites)25 134

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, certain biologic response modifiers, corticosteroids, cytotoxic drugs, radiation)

Potential for decreased immune response to vaccines1 105 134 135

Anti-B-cell antibodies (e.g., rituximab): Optimal time to administer vaccines after such treatment unclear134 135

Corticosteroids: May reduce immune responses to vaccines if given in greater than physiologic doses134

Chemotherapy or radiation: Give inactivated vaccines ≥2 weeks before or defer until ≥3 months after such therapy if immunocompetence restored134 135

Anti-B-cell antibodies (e.g., rituximab): Give inactivated vaccines ≥2 weeks before or defer until ≥6 months after such treatment105 134 135

Certain biologic response modifiers (e.g., colony-stimulating factors, interleukins, tumor necrosis factor [TNF] blocking agents): Give inactivated vaccines ≥2 weeks prior to initiation of such therapy;105 134 if inactivated vaccine indicated in patient with chronic inflammatory illness receiving maintenance therapy with a biologic response modifier, some experts state do not withhold the vaccine because of concern about exacerbation of inflammatory illness105 135

Corticosteroids: Some experts state give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive corticosteroid therapy if feasible,105 134 but may be given to those receiving long-term corticosteroid therapy for inflammatory or autoimmune disease105

Meningococcal vaccine

MenACWY-D (Menactra): Concurrent administration with 9vHPV and Tdap (Adacel) at 3 different injection sites in adolescents 11 through 15 years of age did not interfere with antibody responses to any of the vaccine antigens;1 increased incidence of swelling at 9vHPV injection site compared with administration of 9vHPV alone1

Meningococcal group B vaccine (MenB-FHbp; Trumenba): Concurrent administration with 4vHPV (no longer available in US) in adolescents 11 to <18 years of age did not interfere with antibody response to MenB-FHbp or to 3 of the 4 antigens in 4vHPV209 210 211

May be administered concurrently (using different syringes and different injection sites)1 233

Tetanus toxoid and reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap)

Tdap (Adacel): Concurrent administration with MenACWY-D (Menactra) and either 4vHPV (no longer available in US) or 9vHPV at 3 different injection sites in adolescents did not interfere with antibody responses to any of the antigens;1 increased incidence of swelling at HPV vaccine injection site compared with administration of HPV vaccine alone1

May be administered concurrently (using different syringes and different injection sites)1 134 199

Stability

Storage

Parenteral

Suspension, for IM Use

2–8°C.1 Should be administered as soon as possible after removal from refrigeration, but can be kept between 8–25°C for up to 72 hours.1 Protect from light and freezing.1

Does not contain thimerosal or any other preservatives or antibiotics.1

Actions

  • HPV vaccine (9vHPV) is a suspension of VLPs of the major capsid proteins of 9 HPV types, including 7 high-risk (oncogenic) types (HPV types 16, 18, 31, 33, 45, 52, and 58) and 2 low-risk (nononcogenic) types (HPV types 6 and 11).1 202 The type-specific VLPs are prepared separately using recombinant DNA technology in S. cerevisiae; purified by a series of chemical and physical methods; and adsorbed onto preformed aluminum-containing adjuvant (amorphous aluminum hydroxyphosphate sulfate).1

  • HPV vaccine VLPs are structurally indiscernible from native HPV virions and stimulate active immunity to the HPV types represented in the vaccine.4 5 12 14 The VLPs do not contain DNA and are noninfectious.4 5 12 14

  • High-risk HPV types 31, 33, 45, 52, and 58 cause about 14% of HPV-associated cancers in females (approximately 2800 cases annually) and 4% of HPV-associated cancers in males (approximately 550 cases annually).202 203

  • Low-risk HPV types 6 and 11 cause about 90% of all cases of genital warts and high-risk HPV types 16 and 18 cause about 70% of all cases of cervical cancer, AIS, CIN 3, VIN 2/3, and VaIN 2/3 and 50% of all cases of CIN 2.105 166 201 202 344

  • Vaccination with a 3-dose series of 9vHPV can prevent diseases caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, including genital warts caused by HPV types 6 and 11; cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; and precancerous anal and genital lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.1 202 204

  • Data indicate that ≥99.5% of female and male vaccine recipients 9 through 26 years of age develop antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 by 1 month after the third dose of 9vHPV.1 202 207

  • Immune response to a 2-dose regimen of 9vHPV in females and males 9 through 14 years of age is noninferior to that reported with a 3-dose regimen of 9vHPV administered to females 16 through 26 years of age.1 207 208

  • Minimum antibody titers that provide protection against infection with HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 not established to date.1

Advice to Patients

  • Prior to administration of each vaccine dose, provide copy of manufacturer’s patient information to the patient and/or patient’s parent or guardian.1 Also provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative (VISs are available at [Web]).1 59

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of HPV vaccination.1

  • Advise patient and/or patient’s parent or guardian that HPV vaccine does not provide protection against disease from vaccine and nonvaccine HPV types that an individual has previously been exposed to through sexual activity.1

  • Advise patient and/or patient’s parent or guardian that vaccination with HPV vaccine is not a substitute for routine cervical cancer screening.1 Vaccine recipients should continue to receive routine cervical cancer screening (e.g., Pap tests) according to current guidelines for such testing.1 105 201 202 344

  • Advise vaccine recipients not to discontinue anal cancer screening if it has been recommended by a health-care provider.1

  • Advise vaccine recipients to continue to practice behaviors that limit the risk of HPV exposure (e.g., sexual abstinence, monogamy, limited number of sexual partners, use of condoms).19 201 344

  • Importance of completing the vaccination series of HPV vaccine, unless contraindicated.1

  • Advise patient and/or patient’s parent or guardian that fainting, sometimes resulting in falling with injury, has been reported following vaccination with HPV vaccine and the patient should be observed for 15 minutes after administration.1 19

  • Importance of contacting clinicians if a hypersensitivity reaction (difficulty breathing, wheezing, hives, rash, swollen glands [neck, armpit, or groin], joint pain, weakness, chest pain) occurs following a vaccine dose.1 Clinicians or individuals can report any adverse reactions that occur following vaccination to VAERS at 800-822-7967 or [Web].1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise vaccine recipients that HPV vaccine is not recommended for use in pregnant women1 19 28 or women who plan on becoming pregnant during the vaccination series.1 If any exposure to HPV vaccine occurs around the time of conception or during pregnancy, vaccinees and their clinicians are encouraged to contact the pregnancy registry at 800-986-8999.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Human Papillomavirus 9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Vaccine, Recombinant

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

30 mcg of HPV type 6 L1, 40 mcg of HPV type 11 L1, 60 mcg of HPV type 16 L1, 40 mcg of HPV type 18 L1, 20 mcg of HPV type 31 L1, 20 mcg of HPV type 33 L1, 20 mcg of HPV type 45 L1, 20 mcg of HPV type 52 L1, and 20 mcg of HPV type 58 L1 protein per 0.5 mL

Gardasil 9

Merck

AHFS DI Essentials™. © Copyright 2020, Selected Revisions November 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Merck & Co. Gardasil 9 (human papillomavirus 9-valent vaccine recombinant suspension for intramuscular injection prescribing information. Whitehouse Station, NJ; 2018 Oct.

4. Siddiqui MA, Perry CM. Human papillomavirus quadrivalent (types 6, 11, 16, 18) recombinant vaccine (Gardasil). Drugs. 2006; 66:1263-71. http://www.ncbi.nlm.nih.gov/pubmed/16827602?dopt=AbstractPlus

5. Villa LL, Costa RL, Petta CA et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005; 6:271-8. http://www.ncbi.nlm.nih.gov/pubmed/15863374?dopt=AbstractPlus

12. Ault KA. Vaccines for the prevention of human papillomavirus and associated gynecologic diseases: a review. Obstet Gynecol Surv. 2006; 61:26-31S.

14. Dunne EF, Markowitz LE. Genital human papillomavirus infection. Clin Infect Dis. 2006; 43:624-9. http://www.ncbi.nlm.nih.gov/pubmed/16886157?dopt=AbstractPlus

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