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  • HPV and Cervical Cancer, Screening and Prevention

    John Ragsdale, MDJuly 12, 2018

    CME Lecture Series

    PresenterPresentation NotesThis is a topic of medicine which is continuing to evolve we will look at the progresss we made around screening, vaccinations and look at cases
  • We have come a long Way

    PresenterPresentation NotesRates of cervical cancer have dropped to roughly of what they were in the seventies. In fact from the 1930s we have seen an 80% decline in the morbidity associated with cervical cancer
  • Prevalence HPV in Young Adults in U.S

    PresenterPresentation NotesYou will notice that happily, the rates are dropping due to increased rates of vaccination in the U.S. In fact you totaled the prevalence of all HPV serotypes from folks aged 18-59 anyone want to hazard a guess as to that %?
  • 25% all cervical cancers

    90-95% of warts

    20% of all adeno-carcinomas

    55-60% of All cancers

    16 18

    The rest6,11

    HPV genotypes

    PresenterPresentation NotesIf you know these statistics then you know why HPV 16 and 18 were originally the focus of so much energy and research So not all HPV is created equal most strains rarely if ever cause a problem And mostly they do not cause symptoms (hence the high prevalence)
  • PresenterPresentation NotesDo you know what your vaccination rates are? Do you have system of reminders? What strategies are you using to motivate parents and kids to get vaccinated?we are not doing a very good job at vaccinating in NC we are below the national average Hep B discussion
  • HPV Vaccines Gardisil 9:

    6, 11, 16, 18, 31, 33, 45, 52, and 58

    Gardisil: 6, 11, 16, and 18

    Cervarix: 16 & 18 For girls only

    PresenterPresentation Notes16 & 18 cause 70 % of all HPV mediated cancers do you know which you are offering in your clinicThese vaccines as we will see are effective but you have to use themThey will likely eventually cause a change in how we screen We do not know how long protection lasts that is a very active field of study
  • How Effective is the HPV vaccine? Answer very!!! Large RCT of 2392 women ages

    16-23 split into two groups. All women were tested for HPV virus at enrollment One group was placebo

    Rate of persistent HPV infection 3.8% One group got series of 3 HPV 16

    vaccines at 0,2,and 6 months Rate of persistent infection 0%

    A controlled trial of a human papillomavirus type 16 vaccine.Koutsky LA1, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU; Department of Epidemiology, University of Washington, Seattle, USA. kouts@u.washington.edu

  • HPV vaccine: efficacy HPV Cancers U.S.

    2008-12: 38,793 HPV-associated

    cancers (11.7 per 100,000 persons)

    23,000 (13.5) among females

    15,793 (9.7) among males.

    30,700/38,793 = HPV attributed

    28,500/38793 = Preventable

    Human PapillomavirusAssociated Cancers United States, 20082012 MMRW Weekly / July 8, 2016 / 65(26);661666



    HPV Cancers38,793

    Women Men

    74% Preventable

    PresenterPresentation NotesTwo things on this slide caught my attention first the high number of preventable cancers and secondly the relatively high number of men that end up with HPV related cancers. What % of HPV is detected in all SCC and adenocarcs?: 99.7%
  • Risk Factors

    PresenterPresentation NotesSmoking is assoc with SCC but NOT adenocarcRisk decreases by 50% after 10 yrs of quitting OCPs for 5-9 years assoc with hazard ratio of 2 effect is hormonal may be result of sex steroids on oncogenic expression BUT CIN is not a contraindication to OCPs
  • Cervical Cancer Screening

    Being rarely or never screened is THE major contributing factor to the MOST cervical cancer deaths today.

    PresenterPresentation NotesAccording to the CDC Who is not screened?Minorities Low SESForeign born and has lived in the U.S. less than 10 yearsNo usual source of health care or fragmented healthcare
  • Cervical Anatomy


    Squamous epithelium

    Transformation zone

    Columnar epithelium


    SC Junction

    PresenterPresentation NotesSo the cervix is a busy place cytologically -cells are changing from columnar to squamous (column to plate)It is forever transforming and remodeling which is required for it to function normally So this is just a reminder about whats going on within the cervix anatomically and remember overtime the SC junction tends to migrate up into the OS making colposcopy more difficult
  • SETZ



    TZ: transformation zone

    SCJ: squamo-columnar junction

    SE: squamous epithelium

    CE: columnar epithelium

    PresenterPresentation NotesJust as a quick reminder about anotomyFrom central to peripheral
  • Review of Pap Nomenclature & Results

  • A bit of Context. Bethesda system

    System for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014.

    ASCCP: Governing body Devised rationale cytological definitions

    then correlated with pathologic definitions Established Guidelines:

    Based on data from 1.4 million women followed from Jan 2003 December 31st 2010 at Kaiser

    PresenterPresentation NotesStandardization began in the 80s when physicians began to realize there was no standard way of discussing pap abnormalities, and consequently, no standard parameters for treatment
  • Reflecting our evolving understanding HPV pathology

    The ASCCP will no longer be referenced as the American Society for Colposcopy and Cervical Pathology but rather now simply as the ASCCP, with a mission to improve lives through the prevention and treatment of ano-genital and other HPV-related diseases.

    PresenterPresentation NotesFrom their webpageMission for the ASCCP recently updated to reflect our increasing understanding of the role HPV plays in the development of cervical pathology and more importantly and a rising emphasis on non cervical based HPV pathology we will be looking at slides later on of the broader disease burden the HPV is responsible for I think you will be surprised at the %s
  • HPV testing: a game changer

    An increased detection of CIN3

    Concomitant decrease in

    CIN3+ or cancer

    detected in subsequent screening

    increased diagnostic lead time

    Longer screening intervals

    PresenterPresentation Notes40% more sensitive at detecting CIN3+ however they have a lower specificity
  • HPV testing: a game changer

    Enhanced detection of women with adenocarcinoma of the cervix and its precursors

  • Bethesda System CIN System Dysplasia

    ASCUS Cellular Atypia Unspecified Changes

    ASC-H Cannot r/o high grade Variable

    LGSIL CIN 1 Mild Dysplasia


    CIN 3

    Moderate Dysplasia/Severe Dysplasia

    Cytologic Pathologic



    PresenterPresentation NotesThe bottom two are cancer equivalents It was the conferences with the ASCCP with the foundational work by the Bethesda group that began to bring
  • ASCUS ASCUS H nuclear enlargement in Pap tests is due to reactive change

    About 4% of total pap results

    Not a cancer equivalent but evidence of infection

    First exclude moderate/severe cervical intraepithelial neoplasia or carcinoma in-situ (CIN3/HSIL)

    A rare but significant finding of a cancer equivalent

    2% have cancer at time of pap

    20% will go on to get cancer without proper care

    PresenterPresentation NotesNo cellular designation was originally more problematic than ASCUS during the first Bethesda meeting in 1988Colposcopist dont like ASCUS H
  • LGSIL / CIN 1 What % of low grade pap smears progress to CIN2 or greater?

    A)12-16%B)Less than 3%C)18-22%

    Mildly increase nuclear/cytoplasmic ratioMild/moderate staining

  • What happens to LGSIL?

    60% of CIN 1 regresses

    30% of CIN 1 persists

    10% progress to CIN 3

    1% may ultimately go on to invasive cancer


    Increased nucleoplasm to cytoplasm ratio

    Moderately to severely abnormal morphology

    Chromatin is more granular

    Nuclear notches and folds

    Nucleus is more hyper chromic

  • Cervical cancer

    Screening: Adolescents

    Care for contraception of STI screening / treatment is paramount

    NO pap test NO speculum exam

    for asymptomatic women

    STI screening can be done using urine

  • Treatment Saves Lives, but there is a cost.

    After LEEP women are more likely to have Preterm birth (O.R 1.7 Low birth weight (O.R. 1..8) PPROM (O.R. 2.7

    Increased risk (small) with perinatal death from incompetent cervix

    Risk rises with depth and number of LEEPs Conization vs. laser treatment risks

    essentially the same Absolute risk is quite small

  • Case 1

  • CASE 1

    A 21 year-old G0P0 presents to your office for her first gynecologic examination.

    She has no symptoms or complaints and does not report chronic medical conditions.

    She does not smoke or use illicit drugs.

    She has had two male sexual partners in her lifetime and has been using combination oral contraceptive pills for the past 14 months.

    She has completed her HPV immunization series

  • What is the screening interval for a 21 year old female?

    Pap and co-testing every three years

    Pap only every three years Pap only every 5 years Annual pap smear

  • Cervical Cancer Screening Women under 30

    HPV testing should not be used to screen

    NOT as a function of co-te


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