Madison Clinic
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Screening for Cervical Cancer

PAP screening should begin within three years of the onset of sexual activity
or at the age of 21 in a patient with an uncertain history of sexual activity. HIV+ patients should be screened every six months during their first year of diagnosis and then yearly if the initial tests are negative.

Screening for cervical cancer is of particular concern for HIV infected women since the incidence of cervical dysplasia is 4 to 5 times higher in HIV-positive women as compared to HIV-negative women. Cervical dysplasia is common in HIV infected women because: 1) both HIV and HPV are sexually transmitted, and 2) HIV
infected women are more likely to have persistent HPV infection, and 3) Persistent infection with one or more oncogenic HPV subtypes is a major factor
in pathogenesis of pre-malignant and malignant cervical disease.

Given the increased risk of cervical cancer in HIV+ patients, screening should continue on a yearly basis indefinitely. Women who have had hysterectomies for benign reasons and no longer have their cervix do not need PAP smears. Women who have hysterectomies for cancer or severe dysplasia should continue to
have PAP smears to sample cells from their vaginal vaults to screen for vaginal cancer.

Pap Smear Results

The pathology department at HMC more or less follows the revised Bethesda
system nomenclature. Please note that the terms CIN1, CIN2, or CIN3
(cervical intra-epithelial neoplasia) are diagnoses made by biopsy and not with
a PAP smear. Below you will find the recommendations from the 2006 Consensus Guidelines for the initial evaluation of each given PAP smear abnormality.

ASCUS – atypical squamous cells of undetermined significance

ASC-US is quite common in HIV-infected women. Previously, based on studies that had reported a high prevalence of both HPV DNA positivity and significant cervical pathology in this population, it was recommended that all immunosuppressed women with ASC-US undergo colposcopy. More recent studies have found a lower prevalence of CIN 2,3 and HPV DNA positivity; therefore, immunosuppressed women should be managed in the same manner as women in the general population.
The preferred evaluation is based on reflex HPV testing for ASCUS and referral to colposcopy for positive HPV results. If negative HPV results, repeat cytology in 12 months. If at 12 months results are still ASCUS or higher, refer for colposcopy regardless of HPV results.
In post-menopausal women with evidence of vaginal atrophy, it is acceptable to treat the vaginal atrophy and repeat cytology screen in 1 year.

ASC-H – atypical squamous cells, cannot rule out HSIL

If result shows ASC-US: cannot exclude High-Grade SIL, refer for directly for colposcopy.
For adolescent women (females 20 years and younger) with ASC-US or LSIL, repeat cytology q 12 months for 2 years regardless of HPV results. If persistent ASC-US or LSIL for > 2 years, refer for colposcopy.

AGC-AIS – atypical glandular cells, endocervical adenocarcinoma in situ

Although uncommon , there is a high likelihood the patient will be found with CIN, biopsy proven AIS, or invasive cervical cancer. In addition, the traditional methods to evaluate AGC (ie repeat cytology, colposcopy, and endocervical sampling) have low sensitivities for glandular carcinoma. Therefore an aggressive and invasive approach is warranted in women with this cytologic abnormality. Women with all subcategories of AGC, except atypical endometrial cells, should have colposcopy with endocervical sampling, HPV DNA testing and endocervical curettage. Women over 35 years old or those with abnormal vaginal bleeding should receive an endometrial biopsy. Women with atypical endometrial cells should have endometrial and endocervical sampling and if no pathology should be referred for colposcopy.
The recommended postcolposcopy management of women of known HPV status with atypical endocervical, endometrial, or glandular cells NOS who do not have CIN or glandular neoplasia identified histologically is to repeat cytologic testing combined with HPV DNA testing at 6 months if they are HPV DNA positive and at 12 months if they are HPV DNA negative. Referral to colposcopy is recommended for women who subsequently test positive for highrisk (oncogenic) HPV DNA or who are found to have ASC-US or greater on their repeat cytologic tests. If both tests are negative, women can return to routine cytologic testing.

LSIL – low-grade squamous intra-epithelial lesion

In general, these patients should be referred for colposcopy . If no CIN 2 or 3, repeat cytology at 6 & 12 mos OR repeat HPV DNA testing @ 12 mos. (This is a major change in guidelines as we used to follow these women with persistent LSIL with colposcopy every 6 mos).
However, in post-menopausal women with evidence of vaginal atrophy, it is acceptable to treat with intravaginal estrogen therapy and repeat Pap in 6-12 months. Refer to colposcopy if persistent changes.

HSIL – high-grade squamous intra-epithelial lesion

An immediate loop electrosurgical excision or colposcopy with endocervical sampling is acceptable for managing women with HGSIL. In women with HSIL cytology result, who are poor candidates for continued follow-up, consider referring directly for LEEP instead of colposcopy.
When CIN 2,3 is not identified histologically, either a diagnostic excisional procedure or observation with colposcopy and cytology at 6 month intervals for 1 year is acceptable, provided in thelatter case that the colposcopic examinationis satisfactory and endocervical sampling is negative
In adolescents with HSIL, colposcopy is recommended. Immediate loop electrosurgical excision (ie, “see-and-treat”) is unacceptable in adolescent women. When CIN 2,3 is not identified histologically, observation for up to 24 months using both colposcopy and cytology at 6-month intervals is preferred, provided the colposcopic examination is satisfactory and endocervical sampling is negative.

Management of Abnormal PAP smears during pregnancy

Management of the above lesions during pregnancy becomes increasingly difficult with increasing severity of the cytologic lesions. Colposcopy with biopsy is safe during pregnancy. However, endocervical curettage and invasive cervical biopsy procedures are contraindicated during pregnancy. The decision for colposcopy is unchanged during pregnancy. In the absence of invasive disease, additional colposcopy and cytologic evaluation is recommended. In the absence of invasive disease, treatment of lesions is unacceptable. A diagnostic excisional procedure
(ie cone biopsy) is recommended only if invasive disease is suspected.
Reevaluation with cytology and colposcopy is recommended no sooner than
6 weeks postpartum for pregnant women with HSIL in whom CIN 2,3 is not diagnosed.

Management of Women with Atypical Squamous Cells of Undetermined Significance


[click on image to enlarge]

References:

2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests.

Managment of Women with Atypical Squamous Cell of Undetermines Significance
[algorithm]

Suggested Pap Smear Referral Guidelines (Dec 2007)
(Prepared by HMC Ambulatory Care Medical Directors)

Wright, Thomas et al, 2001 Consensus Guidelines for the Management
of Women with cervical cytological abnormalities, JAMA 287 (2002):2120-2129.

USPTF, Screening for cervical cancer: recommendations and rationale, http://www.ahrq.gov/clinic/uspstf/uspscerv.htm from 2001.

Dr. Liss's Guidelines

INITIATION/CESSATION OF SCREENING: Pap screening should begin
at age 21.  There are no specific recommendations for earlier screening of women with HIV, women who become sexually active or are abused at a very young age,
or women perinatally infected with HIV. Given the increased risk of cervical cancer
in HIV-infected women, screening should continue on a yearly basis indefinitely. Women who have had hysterectomies for benign reasons, have never had a
history of CIN 2 or 3, and no longer have their cervix do not need ongoing PAP smears. Women who have had hysterectomies for cancer or high-grade dysplasia (CIN 2 or 3) should continue to have annual PAP smears for at least three years
to sample cells from their vaginal cuffs to screen for cancer.

FREQUENCY OF SCREENING: Annually.  There is no role for using combination Pap/HPV DNA screening on normal Paps to ascertain whether the screening interval can be increased to q3 years, as women with HIV will continue to require annual screening.  Women should get 2 Paps in their first year of HIV diagnosis or entry into care and then can assume annual screening if both tests are benign. 

WHEN TO TEST FOR HPV:  This is an area of significant controversy and little guiding data.  The American Society for Colposcopy and Cervical Pathology
(ASCCP) recommends reflexive testing for HPV when results of a Pap smear are ASCUS (regardless of HIV status), and if HPV is negative, then repeat Pap in
1 year, and if HPV is positive, refer to colposcopy.  The CDC OI Guidelines
state that there is not enough compelling data to use HPV in any setting in
women with HIV.  Our recommendations from the available data are:  Only
order HPV if Pap results are ASCUS.  DO NOT order HPV with normal Pap
smears.  The only other setting in which HPV should be ordered is if recommended in follow-up after an abnormal Pap smear, colposcopy, or treatment for cervical dysplasia.  At this time, HPV type specific testing is available, but has no clear role in management of the HIV positive woman and as such should not be ordered.
  If for some reason a patient with a normal Pap is tested for HPV and HPV is positive, a repeat Pap smear and HPV testing
should be performed in 12 months. If both are negative, you can resume annual
Pap screening.  If the Pap smear demonstrates greater dysplasia than ASCUS, "
or if repeat HPV is positive, refer to colposcopy regardless of the Pap result.

WHEN/HOW TO REFER TO COLPOSCOPY:  If a Pap smear result is
ASCUS-HPV positive, or demonstrates more advanced dysplasia than ASCUS,
refer to colposcopy.  In some instances, repeat colposcopy will also be
recommended as follow-up of dysplasia proven by colposcopy.  At this
point and for the indefinite future, all colposcopies will occur in the Women’s Clinic, specifically at the Dysplasia Clinic.  When arranging for colposcopy, there are 3 steps:

1) Write a referral to Colposcopy or Dysplasia Clinic within the HMC Women's Clinic and file it as you normally do with any referral.

2) You will also likely receive a note in your ORCA inbox informing you that your patient has an abnormal Pap result and requesting a plan.  YOU MUST OPEN THIS MESSAGE AND "MODIFY" IT WITH AN ADDENDUM STATING YOUR PLAN.  
THIS CAN BE VERY SIMPLE, I.E. REFERRAL TO DYSPLASIA CLINIC FOR COLPOSCOPY WRITTEN. This will allow the HMC Pap trackers to know what
your plan is, stop nagging you, and look out for your referral.  This will also
signal the Pap trackers to send a letter to your patient with the plan.  Some
of our patients are very concerned about receiving materials from the hospital
and if this is a concern, you will need to write in your addendum THAT A LETTER SHOULD NOT BE SENT and that you will contact the patient yourself.  
Unfortunately, if the Pap is normal, at this point, a letter is sent to the patient automatically.  If you are concerned about this, I would recommend you contact Autumn Kriofske (ck6@u.washington.edu) and request that no letter be sent.

3) Ideally you would also call your patient and tell them about their abnormal
result and their need for a colposcopy.  If folks have questions as to how this conversation should be conducted, feel free to contact me.  If you do not call,
your patient will get a letter, which will likely be a bit of a shock and may engender more stress and phone calls for you in the long run.

FOLLOW-UP AFTER COLPOSCOPY:  After colposcopy, the providers in
Women’s Clinic will send you and your patient a letter stating the follow-up
plan.  In that note, they generally state what tests will need to be performed and when, as well as whether they need to be performed at Women’s Clinic or by you.  PLEASE incorporate this information into your note.  Frequently these follow-up plans are not documented in Madison Clinic provider notes, and we therefore
are not providing appropriate follow-up.  Also be aware that if the follow-up recommendation is “colposcopy at Women’s Clinic in 6 months or 1 year,” you
may have to re-refer the patient to make this happen—unfortunately, referral back to Women’s Clinic for repeat colposcopy does not seem to happen automatically.

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