Gyn 2012 Practice Guidelines Update

Robert J Kahler, MD FACOG Genesis OBGYN

3 common issues   Gyn Ultrasound

  Incidental Gyn Ultrasound findings   Ovarian cysts

  Thick endometrial echo

  Postmenopausal bleeding

  Pap smear routines

  New OC hormone free intervals

Incidental ultrasound findings

SRU: Society of Radiologists in Ultrasound

2010 Consensus Conference Statement on Asymptomatic Adnexal Masses

Guideline use should avoid patient (and provider) anxiety and limit the need for f/u exams for benign physiologic and clinically inconsequential adnexal cysts

Levine D, et al Management of Asymptomatic Ovarian and Other Adnexal Cysts Imaged at US. Ultrasound Quarterly 2010;26:121-131

Normal Ovaries “make cysts for a living”

 

“Simple” Ovarian cyst

 Unilocular

 Anechoic   No echogenic material within

 Thin capsule  No solid element

 No Doppler flow (Blood flow)

 Less than 7 cm

“Complex” Ovarian cyst

 Echogenic material within mass

 Septations

 Thickened capsule

 Solid elements

 Doppler flow

 Size > 7-10cm

Complex ovarian cyst

Ovarian Cancer “Pay attention to the donut, not the hole”

“Simple” Ovarian cyst (SRU)

  Virtually never malignant

  Premenopausal simple or hemorrhagic   <3cm need no reporting or f/u   3-5cm should be described as almost cert benign, no f/u   5-7cm simple, almost cert benign, annual f/u recommended   >5cm hemorrhagic, benign, f/u sono 6-12 weeks

  Postmenopausal   <= 1cm, clinically inconsequential, need no reporting (~20%)   1-7cm, benign, recommend annual sono f/u once stable

  CA125 helps triage

  >7cm simple recommend further eval

Question

  Your 63 mother-in-law tells you a 4cm ovarian cyst was found by ultrasound f/u of an MRI of her back. She has no gyn complaints. It is described as unilocular, anechoic, thin walled, and with no doppler flow. The other ovary is unremarkable and there is no free fluid. She asks your advice. You tell her:

1.  Obtain a CA125 and, if normal, repeat sono in 2 months. If stable, observe by ultrasound

2.  You’ll get her in to your Gyn Oncologist colleague.

3.  Her Gyn should take it out.

Summary: Incidental simple ovarian cysts

  3-7cm premenopausal   <3cm consider functional, <5cm benign and don’t follow

  1-7cm postmenopausal   < 1cm clinically inconsequential

  Unilocular, anechoic, thin walled w/o solid element, no doppler

  Very low malignant potential

  Observe until stable (ie q2mo, then 4mo, then 6mo) then annually

Endometrium

Postmenopausal Bleeding

  Endometrial cancer until proven otherwise

  H&P may find vulvar, vaginal, or cervical pathology   Issues of hormone therapy   Higher risk with obesity, DM, HTN

  Transvaginal ultrasound (TVUS)

  Endometrial biopsy (EMBx)

  Saline Infusion Sonography (SIS)

  Hysteroscopy, hysterectomy

Ultrasound as initial w/u of Postmenopausal Bleeding

 Transvaginal Ultrasound has an extremely high negative predictive value (> 99.4%) and can be used to exclude endometrial pathology   The endometrial echo must be reliably seen   Measures <=4mm

  Risk 1:917   Use clinical judgment

  Persistent bleeding   Risk factors, ie obesity

  ACOG Committee Opinion #440 8/09 (Reaffirmed 2011)

AUB Algorithm

Perimenopausal AUB

TVUS

SIS

EMBx Hysteroscopy

Reliable and thin

<= 4mm

<= 2mm each Global >2mm each

Not reliable +/or not thin

Focal or unsatisfactory

Goldstein SR AJOG 1997;177:102-8

DUB

Saline infusion sonography

AUB Algorithm

Perimenopausal AUB

TVUS (433pts)

SIS

EMBx 2.3%

Hysteroscopy 16%

Reliable and thin

<= 4mm 65%

<= 2mm each 16%

Global >2mm each

29% unreliable 71% >5mm

Focal or unsatisfactory

13.4% polyp 5.3% myoma 3.5% EH

Goldstein SR AJOG 1997;177:102-8

DUB 79%

Post Menopausal Bleeding Algorithm

PMB

TVUS

Observe

EMBx

Gyn Onc

SIS

Refer to Gyn for further evaluation

Reliable and thin

<= 2mm each Cancer

<=4mm

Anything else

Anything else

Gyn

“Thickened endometrial echo” as an incidental imaging finding

  Hysteroscopy for 82 asymptomatic PM thick EM1

  67 (82%) inactive polyps, 7 myoma, 6 atrophy, no Ca or complex hyperplasia. (3.6% complication rate)

  Asymptomatic polyps common, up to 17%2

  < 4/1,000 Ca in 1152 asx PM polyps by SIS (1% complix rate)3

  Cancer dx w/in 8 weeks of bleeding did not change prognosis4

1  Lev-Sagie A et al BJOG 2005;112:379-382

2  Berliere et al Euro J Ca 2000;36:S35-6

3  Ferrazzi E et al AJOG 2009,200: 235

4  Gerber et al EurJCa 2001;57:64-71

Summary: Endometrial ultrasound

  Post menopausal bleeding   Adequately visualized <= 4mm has a very high negative

predictive value and reliably excludes pathology   >4mm work up with SIS, EMBx   Hysteroscopy for inadequate eval, hyperplasia, focal

lesions

  An incidental (no bleeding) “thick” endometrial echo   is common, possibly up to 10-17%   not a good predictor of endometrial pathology   Automatic endometrial sampling may not be justified

  may lead to unintended problems

  Clinical judgment is important in high risk

Pap Smear routines

 ASCCP.org   American Society for Colposcopy and Cervical Pathology

  2012 algorithms for pap smear and HRHPV frequency   Saslow D. ACS, ASCCP, ASCP Screening Guidelines for the

Prevention and Early Detection of Cervical Cancer. J Lower Genital Tract Disease 2012

  Algorithms for recommended f/u of abnormal paps

  Algorithms for recommended f/u of abnormal colpo biopsy

ACS, ASCCP, ASCP Screening Guidelines 2012

 ACOG.org   Chelmow D, et al. The Evolution of Cervical Screening

and the Specialty of OBGYN. OG 2012;119:695-9

 American Cancer Society   http://Caonline.AmCancerSoc.org March 14 2012

 US Prev Serv Task Force

Pap background   George Papanicolau 1883-1962

  Cervical cytology evaluation (manual, automated)

  A routine for over 60 years (pub. 1943)   50% reduction in Cx Ca 1975-2006 (15 to 6.5/100K)

  Potential errors (in a 36 mo Kaiser study*)   Sampling

  Patient (56% w/ Ca never screened)   Good technique

  Liquid based filters out contaminates   Interpretation (32%)

  Inconsistency among cytologists (>50%)   Follow up (13%)

  Where we come in

  Retrospective of Cx Ca at Kaiser. Leyden MA JNCI 2005;97

High Risk Human Papilloma Virus DNA testing (HRHPV)

  Cervix cancer: 1st human cancer identified to have a single necessary cause   Found in 99.7% of cervix cancers   13 HPV types considered high risk, types 16 and 18 account for 70%   Downside: almost everyone has HPV at some time   Upside: >90% clear it within 1-2 years   Viral persistence and the development of high grade dysplasia are key

  Accurate detection by PCR from a cervical sample   >20% in under 25yo, <10% over 30yo   Higher detection with more, and more recent sex partners

  High negative predictive value when “not detected”   Risk of cancer < 1/1,000

High Risk Human Papilloma Virus DNA testing (HRHPV)

  Add later as “reflex” for an abnormality on pap

  With pap to decrease the pap frequency

  F/u previous abnormal cytology or histology

  As primary sample with reflex pap if detected   Not considered standard

  Reported as positive/negative or detected/not detected

  Some labs reflex HRHPV+ to 16 and/or 18 detection

Pap results - Squamous   NIL: No intraepithelial lesion

  Satisfactory or unsatisfactory for evaluation   Endocervical cells present or absent (?atrophy)

  LSIL: Low grade squamous intraepithelial lesion   HPV effect, mild dysplasia, CIN1

  HSIL: High grade squamous intraepithelial lesion   CIN2/3, moderate or severe dysplasia, CIS

  ASC- : Atypical squamous cells-   ASC-US: uncertain significance (85%)   ASC-H: cannot rule out High grade SIL

  Similarity between metaplastic and high grade cells   27% >=CIN2, 17% >=CIN3

  Squamous cell carcinoma

Pap results - Glandular

  AGC: Atypical glandular cells   Cervical, endometrial

  AIS: Adenocarcinoma in situ

  Adenocarcinoma

Pap choices

  Pap alone   Slide or liquid based

  Pap with reflex HRHPV for ASC-US   No advantage for reflex with dysplasia or AGC   No benefit of low grade HPV testing

  Pap and HRHPV “co-testing”

  With or without GC/chlamydia testing

New* screening pap guidelines (assuming prior paps normal, immunocompetent, no DES)

  < age 21, no pap

  Age 21-29 (with or without vaccination)   Pap with reflex HRHPV for ASCUS every 3* years

  Age 30-65   Pap and HRHPV cotesting every 5* years “preferred”   Pap alone every 3 years “acceptable”

  > 65yo or after hyst with cervix removed   No pap if no CIN2+ in previous 20 years   Once stopped, do not resume*

  Little evidence supporting annual screening of any type*

Recommended Pap frequency

  Under age 21   Don’t start regardless of sexual debut   0.1% of Cx Ca -- 1-2/Million

  Incidence hasn’t changed in over 40 years

  0.7% of paps HSIL, 75% CIN2 regressed in 3 yrs   Potential adverse effects of f/u leads to net harm

  Anxiety, stigma of STD, discomfort, potential preterm delivery

  STD testing

Recommended Pap frequency

  Age 21-29 (previously normal pap)   Pap with HRHPV reflex if ASC-US every 3 yrs

  Predicted risk CA w/ 3,2,1 yr intervals is 5,5,3/100,000 with 760, 1,080, 2,000 colpos per 1,000

  HRHPV is common—don’t use it as a screening test   Treat ASCUS/HRHPV negative as NIL and continue screen   Colposcopy for ASCUS/HRHPV+ or greater   Not enough evidence to support longer interval

  with history of normal paps or   vaccination (<32% vaccinated, pre-existing HRHPV)

  GC/chlamydia

Recommended Pap frequency   Age 30-65

  Pap and HRHPV cotesting every 5 years “preferred”   0.61% lifetime cancer risk vs 0.39% w/ 3 yr interval

  Fewer colpos and other intervention

  Increased AdenoCa and AIS detection vs pap   HPV more sensitive and reproducible than pap

  Pap every 3 years “acceptable”   0.69% lifetime cancer risk

  Except HIV+, immune suppression, DES exposed, prior CIN2/3

Recommended Pap frequency   Over age 65   No further paps

  With >= 3 consecutive NIL paps and no CIN2+ in the last 20 yrs

  Continued screening until age 90 would   Prevent 1.6 cancers and 0.5 deaths / 1,000

  Add 127 colpos and 58 false positives / 1,000

  Do not restart for any reason once stopped

Recommended Pap frequency   After hysterectomy (no cervix)

  No pap   unless history CIN2/3 or cancer in previous 20 years

  Evidence of negative prior screening not required

  1.8% abnormal pap   1/1,000 VaIN on biopsy,   no cancer

  Primary vaginal cancer 7/million   Don’t resume once stopped for any reason

  including new sexual partner

F/u abnormal pap   ASC-US pap with HRHPV not detected, treat as NIL and cont

screening

  12 month Pap AND HRHPV cotesting   Pap NIL but HRHPV detected (6% risk CIN2+)

  NIL, HRHPV+ but type 16, 18 not detected

  Lack of endocervical cells

  Colposcopy   ASC-US with reflex HRHPV positive   NIL, HRHPV+ and type 16 or 18 are detected   LSIL (except <21yo: rpt pap 12 mo)   HSIL, ASC-H, AGC, AIS

  Routine screening continued 20 years with hx CIN2/3, Cancer   Continue after hysterectomy, age 65

Pap frequency   POBASCAM trial (Netherlands)

  40K women ages 29-56 in cervix screening program   20K with pap alone, 20K with pap + HRHPV

  16,750 in each group followed up at 5 years after appropriate Rx

  RR of disease in 5 years   >= CIN3 was 0.73 (CI 0.55-0.96) (0.45% vs 0.62%)   Cancer was 0.29 (CI 0.1-0.87) (4 vs 14 of 19,500)

  Adding HRHPV to pap lead to earlier detection and Rx

POBASCAM RCT final results. Rijkaart DC Lancet Oncology. 2012;13:78-88

Question

  A 35yo healthy monogamous G3P3 has had normal annual pap smears since she was 18 at your office but missed last year. Do you

1.  Remind her of the necessity of annual paps and obtain one?

2.  Obtain pap and HRHPV and if normal counsel a 5 year interval?

3.  Suggest she could wait another year prior to repeating pap, discussing the potential addition of HRHPV then?

Summary routine pap

  Don’t start until age 21

  Ages 21-29 pap w/ reflex HRHPV for ASC-US q 3 years

  Ages 30-65   Pap and HRHPV q 5 years preferred   Pap w/ reflex HRHPV for ASC-US q 3 years acceptable

  Stop after age 65 with known nml pap history

  No pap after hysterectomy w/o cancer or CIN 2/3

Reconsidering monthly menses

  Monthly menses is a fairly modern concept. Now 12M OC users

  My 7th Great-grandmother in the late 1600s New England had 16 children, 12 survived. With pregnancy and nursing, she would have few unsuccessful ovulations leading to menses

  The ovary (unlike thyroid, etc) is accustomed to suppression   Every other month, during pregnancy, lactation

  No menses in children, lactation, or menopause   Depo Provera (DMPA), Mirena do not provide “menses”

  Original high dose OC designed with 21 active pills and a week break.

Benefits of new formulations

  Retain excellent contraception with lower doses   All OCs reduce risk of endometrial and ovarian cancer   No consistent effect on breast cancer risk   Non-contraceptive benefits on acne, dysmenorrhea, etc

  Lighter, less uncomfortable menses, PMS, mastalgia   Reduce menstrual migraine (beware aura)   Fewer functional cysts leading to pain, tests, surgery

  Amenorrhea for lifestyle considerations

  Less unintended bleeding

New OC: Hormone Free Intervals Old and new pills in new packaging, lower doses

  3 months of active pills followed by a withdrawal bleed   Seasonique and LoSeasonique

  28 active pills per pack with no break   Lybrel (or any monophasic off label)   Extended Nuvaring use

  ½ dose EE in HFI   Mircette, LoSeasonique

  HFI to 4 or 2 days (FSH by rises CD4)   Loestrin24, Lo Loestrin, Yaz, Natazia

Risks

  Unscheduled bleeding   Tends to improve over time

  Confusion   Don’t wait for withdrawal bleed to start new pack

  Cost if manipulating standard 21/7 pill pack (off label) for extended or continuous use

  ACOG Practice Bulletin #110, Jan 2010

  Micks E, Jensen JT. OC… latest formulations. Contemporary OBGYN Feb 2012

Question

  A 23 yo healthy G0 is new to your office and has been using a generic monophasic 20mcg OC. She’s looking for alternatives because she doesn’t like to have menses but other pills have been expensive or caused adverse effects. Do you

1.  Refer her to Gyn

2.  Use her OC without interval (will need 16 packs per year)

3.  Discuss Mirena, DMPA, and Implanon

4.  Suggest monthly withdrawal bleeding is most normal

5.  2 and 3

Summary

  New lower dose OC formulations and packaging can be used to reduce symptoms and reduce or eliminate bleeding

  Pap/HRHPV co-testing has a high negative predictive value and can extend pap frequency to 5 yrs when over age 30

  A reliable <= 4mm endometrial echo by TVUS has a high negative predictive value in the w/u of PMB

  An incidentally found (no bleeding) thick endometrial echo is poorly predictive of endometrial pathology

  A simple ovarian cyst has a high negative predictive value for ovarian cancer