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Human Papillomavirus (HPV) Vaccine

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General Information

  • HPV is associated with development of3
    • anogenital cancer, including cervical, vaginal, vulvar, penile, and anal cancers
    • oropharyngeal cancer
    • genital warts
  • HPV transmission is common between sex partners, likely more frequent from females to males than from males to females1
  • about 90% of genital warts caused by HPV genotypes 6 and 113
  • of > 100 HPV genotypes, 13 genotypes associated with cervical cancer3
    • most cases of all HPV-associated cancer caused by HPV genotypes 16 and 18
    • in United States, HPV genotypes
      • 16 and 18 associated with 66% of cases of cervical cancer
      • 31, 33, 45, 52, and 58 account for another 15% of cervical cancers
  • reported 77% of HPV-positive anal cancers associated with HPV genotype 161
  • reported 72% of oropharyngeal cancers positive for HPV, of which, 61% associated with HPV genotype 161
    • reported 80% of tonsillar and 70% of base tongue cancers positive for 1 of 14 high-risk HPV genotypes
  • pathogenesis of HPV infection
    • epithelial changes associated with cervical HPV infection in women
      • viral particles enter basal layer through small tears in mucosa, infect metaplastic epithelium in ring of mucosa known as cervical transformation zone (ring of active squamous metaplasia where stratified squamous epithelium of ectocervix progressively replaces the glandular epithelium of endocervix)
      • molecular virology of HPV persistence, progression, and invasion poorly understood
        • frequency of precancerous development from mild lesion vs. an equivocal lesion or cytologically normal HPV-infected tissue unknown
        • persistent HPV infection of epithelium in cervical transformation zone causes most cases of cervical cancer
        • Reference - 17826171Lancet 2007 Sep 8;370(9590):890OpenInNew
      • progression from small cervical intraepithelial neoplasia lesion to cancer can take > 10 years (20567185Obstet Gynecol 2010 Jul;116(1):177OpenInNew)
    • anal HPV infection
    • oropharyngeal HPV infection
      • knowledge regarding carcinogenic process from HPV infection to cancer in oropharyngeal squamous cell carcinoma is mostly extrapolated from cervical cancer model
      • oral mucosa is exposed to HPV, HPV-related precancerous lesion may develop if infection persists
      • persistent infection may progress to invasive cancer within 10 years, however, most infections are cleared within 1-2 years
      • no oropharyngeal premalignant disorders have been well established
      • Reference - 28633362Ann Oncol 2017 Oct 1;28(10):2386OpenInNewfull-textOpenInNew

References

References

General references used

  1. Markowitz LE, Dunne EF, Saraiya M, et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014 Aug 29;63(RR-05):1-30OpenInNewfull-textOpenInNew, correction can be found in MMWR Recomm Rep 2014 Dec 12;63(49):1182, commentary can be found in JAMA 2014 Nov 12;312(18):1920OpenInNew
  2. Petrosky E, Bocchini JA Jr, Hariri S, et al; Centers for Disease Control and Prevention. Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2015 Mar 27;64(11):300-4OpenInNewfull-textOpenInNew
  3. American College of Obstetricians and Gynecologists (ACOG). Committee Opinion No. 704: Human Papillomavirus Vaccination. Obstet Gynecol. 2017 Jun;129(6):e173-e178OpenInNew

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T908142, Human Papillomavirus (HPV) Vaccine; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T908142. Registration and login required.
  • Overview and Recommendations

  • Related Summaries

  • General Information

  • KeyboardArrowRight

    Recommendations from Professional Organizations

    • KeyboardArrowRight

      Centers for Disease Control and Prevention (CDC) (supported by American College of Obstetricians and Gynecologists [ACOG])

      • Vaccine selection

      • Timing and schedule of vaccination

      • Vaccine administration

      • Contraindications and precautions

      • Vaccine interchangeability

      • Special populations

    • American Cancer Society (ACS)

    • Additional recommendations from American College of Obstetricians and Gynecologists (ACOG)

  • KeyboardArrowRight

    Licensed Vaccines for Use in the United States

    • General information

    • Vaccine characteristics

  • KeyboardArrowRight

    Efficacy

    • Overall efficacy (any HPV vaccine)

    • 9-valent HPV vaccine (9vHPV)

    • KeyboardArrowRight

      Quadrivalent HPV vaccine (4vHPV)

      • Efficacy for females aged 15-26 years

      • Efficacy for females aged 24-45 years

      • Efficacy for men

      • Efficacy for children < 15 years old

      • Dosing schedules

    • KeyboardArrowRight

      Bivalent HPV vaccine (2vHPV)

      • Efficacy in females ≤ 25 years old

      • Efficacy in females > 25 years old

      • Efficacy in females with HPV infection

      • Comparative efficacy

      • Dosing schedules

      • Coadministration with other vaccines

    • Monovalent vaccines

    • Herd immunity

    • Cost-effectiveness

  • KeyboardArrowRight

    Adverse Effects

    • Reported adverse effects

    • Adverse events not associated with HPV vaccine

    • Pregnancy outcomes

    • Sexual activity-related outcomes

  • KeyboardArrowRight

    Vaccine Uptake

    • Vaccine coverage in United States

    • Adherence

    • Barriers and facilitators to uptake

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • International guidelines

      • United States guidelines

      • European guidelines

      • Asian guidelines

      • Mexican guidelines

      • Australian and New Zealand guidelines

    • Review articles

    • MEDLINE search

  • Patient Information

  • KeyboardArrowRight

    ICD Codes

    • ICD-10 codes

  • KeyboardArrowRight

    References

    • General references used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special acknowledgements

    • How to cite

Topic Editor
Renee Ridzon MD
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Affiliations

Adjunct Associate Professor, Boston University School of Public Health; Massachusetts, United States

Conflicts of Interest

Dr. Ridzon declares no relevant financial conflicts of interest.

Recommendations Editor
Esther Jolanda van Zuuren MD
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Affiliations

Head of Allergy, Dermatology, and Venereology, Leiden University Medical Centre; Netherlands

Conflicts of Interest

Dr. van Zuuren declares no relevant financial conflicts of interest.

Deputy Editor
Alan Ehrlich MD, FAAFP
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Affiliations

Executive Editor, DynaMed; Associate Professor of Family Medicine, University of Massachusetts Medical School; Massachusetts, United States

Conflicts of Interest

Dr. Ehrlich declares no relevant financial conflicts of interest.

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