Common Issues in Gynecology: HPV Testing, Bioidentical Hormones, Common Cervical Lesions

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Common Issues in Gynecology HPV Testing,
Bioidentical Hormones, Common Cervical Lesions

• Carol A. Stamm MD
• Director Womens Services
• High Street Primary Care
• Clinical Assistant Professor Medicine UCHSC

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HPV Testing Which of my patients need HPV
Testing with their pap?

• ASCCP Guidelines are evidence-based largely, but
  rely on expert opinion (29 Professional
  Societies) for clinical situations in which there
  is limited high quality evidence. They are
  guidelines, to be used with physician discretion.
  No set of guidelines are perfect.
• Release of the 2006 ASCCP Consensus Guidelines
  was delayed 13 months because of continued
  discussion.

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HPV Testing Which of my patients need HPV
Testing with their pap?

• After the 2001 ASCCP Guidelines were released,
  the ASCCP unusually released 2004 Interim
  Guidelines to suggest how to cope with combined
  pap and HPV testing.
• HPV testing is now more available and the cost is
  improved.
• Recommendations for how to manage combination pap
  and HPV tests have not been evaluated by a large
  multidisciplinary group.

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HPV Testing Which of my patients need HPV
testing with their pap?

• Key follow-up from the NCI-sponsored ASCUS/LSIL
  Triage Study (ALTS) informs the new guidelines.
• Patients with ASCUS pap smear results ( 4-5)can
  be effectively triaged for colposcopy by ordering
  reflex HPV testing for HIGH RISK HPV ONLY.
  (40-50 )
• This option is not available for conventional pap
  smears, so that patient must have a follow-up pap
  at 6 and 12 months. If both tests are negative,
  continue regular screening. For any higher
  abnormality, or continued ASCUS, she should be
  sent to colposcopy. Immediate colposcopy is also
  an option.

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HPV Testing Which of my patients needs HPV
testing with pap?

• A patient with an ASCUS pap negative for high
  risk HPV at any age has a pap good for one year
  only. Possible explanations recent coitus,
  douching, tampon use, infection, recent menses,
  or trauma or ?
• A patient with an ASCUS pap, positive for HRHPV
  greater than 20, should be treated as if she has
  LGSIL, i.e. she should be referred for colposcopy.

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HPV Testing Which of my patients need HPV
testing with pap?

• ASCUS Cannot Exclude HGSIL, LGSIL, HGSIL should
  be referred for colposcopy without HPV testing if
  patient is over 20 years of age.
• AGUS patients do not need HPV testing they need
  immediate referral to GYN for colposcopy, and
  possible endometrial biopsy. HPV testing may be
  obtained at colposcopy.
• REPEAT PAP UNACCEPTABLE FOR AGUS.

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HPV Testing Which of my patients need HPV
testing with pap?

• Adolescents, defined here as less than 20 years
  of age, are a special case82 are likely HPV
  positive /2yrs
• These adolescent guidelines are less
  evidence-based and are a reaction to the
  complications (PTL) seen in patients w/ leep
  prior to pregnancy.
• Few invasive cervical cancers are diagnosed in
  adolescents.
• Regression approx 90 36 months.
• Colpo for HSIL still recommended.
• Q6 month paps for adolescent with other lesions.
• NO NEED TO ORDER HRHPV ON ADOLESCENTS (
• Brown et al JID, 2005

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HPV Testing

• Revised ACOG Guidelines indicate pap smear
  screening should begin 3 years after onset of
  sexual activity and by 21 if not yet sexually
  active.
• The potential impact of the HPV vaccine was not
  accounted for in the development of these
  guidelines. Use of the vaccine is less than
  expected at this time.
• Models have predicted different pap smear
  screening guidelines for women who received
  complete HPV vaccination in the future.

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HPV Testing Which of my patients needs HPV
testing with pap?

• Pregnant women w/ LSIL may undergo colpo while
  pregnant, and have postpartum follow-up if no CIN
  2-3 or higher lesion noted, or may defer
  colposcopy for 6 weeks postpartum.
• Adolescents( less than 20) w/ ASCUS or LGSIL may
  have repeat cytology in a year. This is a
  significant change, and controversial. You may
  still send the patient to colposcopy.

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HPV testing Which of my patients needs HPV
testing w/ pap?

• Patients 30 years may have pap and HRHPV
  testing. If both negative, the next pap 3 years.
  S 99 10 yr risk CIN 3 1-2
• If the pap is normal and HRHPV is positive, a pap
  is due in a year. (CIN 2 risk 2-5-40-60 turn
  HPV neg w/in 6 months-50-75 by 1 yr)
• If the pap is ASCUS and above and HRHPV is
  positive, colposcopy is needed.

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HPV Testing Who needs HPV w/ Pap?

• For women 30 over who are still HRHPV positive
  at 1 year, colposcopy is recommended.
• HPV 16 pos 20 risk CIN 3 in 10 years
• HRHPV testing is Not for Adolescents,
  twenty-somethings. because of transient
  colonization low risk CIN2.

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HPV Testing Which of my patients need HPV
testing with pap?

• ACOG guidelines have no upper age limit on pap
  smear screening.
• Surprising WHI substudy showed increased risk of
  pap smear abnormalities in women randomized to HT
  (.625 mg CEE 2.5 mg medroxyprogesterone
  acetate)
• 2011 next edition of ASCCP guidelines
  Anticipated issues-frequency of pap smear
  screening in HPV vaccinated individuals

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HPV Testing Which of my patients needs HPV w/
Pap?

• 1. Order it reflexively (i.e. when you get your
  pap result) if result is ASCUS and if your
  patient is not less than 20.
• 2. Consider it on patients over 30 w/ goal of not
  doing another pap for 3 years if both tests are
  negative.
• 3. ONLY order HRHPV. The presence of low risk HPV
  does not cause cancer and only drives up the cost
  and worries the patient.

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HPV Testing

• Wright TC et al 2006 Consensus Guidelines for the
  Management of Women with Abnormal Cervical Cancer
  Screening Tests. AJOG 2007 197 (4) 346-355
• Wright TC et al Interim guidelines for the Use of
  Human Papillomavirus DNA Testing as an Adjunct to
  Cervical Cytology for Screening. Obstetrics and
  Gynecology 2004 103 367-372
• ASCCP.org

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What is the difference in efficacy of
bioidenticals/compounded hormones and
FDA-approved prescription HT preparations?
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Natural Estrogen

• 17- beta estradiol is the estrogen made by the
  ovaries primarily before menopause
• Estrone is the estrogen most abundant after the
  menopause
• CEE is manufactured from a natural source, horse
  urine

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Natural Estrogen

• Final common pathway of metabolism 17ß
  -estradiol is metabolized by
• the liver to
• estrone

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Natural Estrogen

• Neither the NAMS nor the FDA recommend natural
  over Synthetic estrogen because there is no
  evidence that ultimate outcomes are different.
  The recent NIH State-of-the-Science conference on
  menopausal symptoms concurs. (Inadequate Data and
  No Safety Data March 2005)

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FDA FTC Warning

• Thursday, November 10, 2005 the FDA mailed
  Warning Letters 16 companies marketing
  alternative hormone replacement therapies The
  treatments are considered to be unapproved new
  drugs
• The Federal Trade Commission sent 34 letter to
  Web Site Operators citing claims that may be
  false or unsubstantiated and therefore may
  violate the law including progesterone creams,
  sprays and dietary supplements

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FDA FTC WARNINGS

• AllNatural Pain Relief, Bio-health,
  BuyInnovations.com, CHS International Research,
  ComCore 21, Greatest Herbs on Earth, HMS Crown,
  Healthworks 2000, Healthy Days, Heba Laboratores,
  Herbal Fields Supplements, Nutriteam, One Life
  USA, Suzannes Natural Foods, The Way Up, and Tip
  Top Vitamins were given 15 days to respond to the
  FDA www.Kaisernetwork.org Monday, November 14,
  2005

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Natural Estrogen

• January 9, 2008 FDA announced that it warned 7
  pharmacies selling bioidentical hormones over
  the Internet that they were breaking the law with
  false and misleading claims about the benefits
• Deborah Autor, FDA Director of Compliance said
  Claims like these mislead consumers and
  health-care providers with inaccurate
  information.
• FDA position is that there is no reliable
  scientific evidence to support the assertions.

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OTC Progesterone Creams

• Women who rubbed the maximum labeled dose
  Pro-gest had the same blood levels as those
  taking Prometrium (J Clin Pharm 200545614)
• FDA considering making natural progesterone
  creams limited to prescription only
• No randomized, controlled studies support the
  safety and efficacy of progesterone cream alone
  for treatment of menopausal symptoms

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Compounding Treatment

• Special for Me therapy
• Allure of bioidentical hormones
• Adjustment of HT to tenth of a milligram

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Compounding Treatment

• No outcome data
• No evidence for frequent dosage adjustments based
  on serum testing
• No data that saliva testing while taking
  exogenous hormones is valid
• Normal premenopausal estradiol is 40-500 pg/ml

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FDA Survey 2001www.fda.gov/CDER/pharmcomp/survey.
htm

• Tested 29 drugs obtained through mail order
• 34 of the products failed analytical testing
• No data on Colorado compounding pharmacies
• NAMS advises not using non-tested formulations
  when studied options exist

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Possible Solutions

• Establishing an accreditation process for
  compounding pharmacies
• FDA Advisory Panel for pharmacy compounding
• Use caution until steps in places

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Compounding Treatment

• End point should be based on symptom relief,
  goals of treatment, and risk benefit profile

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No Outcome Data Caution Advised

• What is the difference in efficacy of
  bioidenticals/compounded hormones and
  FDA-approved prescription HRT preparations?
• There are no head-to-head trials.
• Most bioidentical and compounded hormones
  studies do not have a control group.
• Known placebo effect of HT studies is 40.

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HT Differences Compounded vs FDA-Approved

• No data other than the progesterone study
• Some FDA-Approved options will likely be removed
  for lack of safety data- estrogen/testosterone
  formulation specifically.
• Data with estradiol suggest serum levels of 80
  pg/ml target range, but no data for other
  formulations.

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Natural Remedies

• Vitamin E 800 IU QD and isoflavones slightly
  better than placebo
• Soy small to no effect
• Black cohosh (Cimifuga recemosa) may be helpful
  German studies limit to 6 months use although
  current German practice is more liberal. (Level
  III Q/A President of European Menopause Society
  January 2006)

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Natural Remedies

• Level 1 evidence that long-term soy isoflavone
  treatment is linked to endometrial hyperplasia
• After 5 years of treatment 3.8 of soy treated
  women had endometrial biopsy demonstrated
  endometrial hyperplasia( vs RR 8 for unoppposed
  estrogen)
• Isoflavone in soy is similar to estradiol

Fertil Steril 2004 82145-148, Unfer V, Casini
ML, et al
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Natural Remedies

• Yam cream ineffective but some manufacturers have
  begun adding progesterone so not all are hormone
  free.
• Avlimil, herbal product without published
  clinical trials. Significant safety concern
  because primary component is sage leaf which can
  lead to neurotoxicity with prolonged use

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Identification of Common Benign Cervical Lesions

• Ectropion
• Nabothian Cysts
• Polyps (Endocervical vs prolapsing endometrial)
• Obstetrical Lacerations
• Cervical Warts (HPV you can see)
• Infectious Causes Cervicitis, Herpes, Chlamydia,
  Gonorrhea, Tricomoniasis, PID

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Dralaamoshbah.blogspot.com

• Ectropion

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www.nytimes.com
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Large Nabothian Cyst
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www.ahealthyme.com
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www.gynae.com sg

• Polyp with long stalk

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www.gfmer.ch
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Hayatcenter.com
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www.medscape.com

• Obstetrical laceration or post-leep

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Cervical Warts (HPV)

• www.manbir-online.com

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Deptswashington.edu

• Cervicitis

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www.nlm.nih.gov

• Cervicitis

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www.deptswash.edu

• Chlamydial Cervicitis

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Identification of Common Benign Cervical Lesions

• Ectropion normal at pubarche, w/ combination
  ocps, during pregnancy
• Nabothian Cysts Epithelial layer occluding gland
  opening
• Endocervical polyp w/ thin clearly visible stalk
  may be removed. Endometrial should be referred.
• Obstetrical lacerations exist require no TX
• Infectious causes should be treated