4/10/05njm

**Q. What are the alternatives to manage CIN 2 in young women?**

A. Managed with LEEP in the past, it can be managed less invasively in a
compliant patient

**Background**

The American Society for Colposcopy and Cervical Pathology (ASCCP)
guidelines <http://www.asccp.org/consensus.shtml> recognize that high
grade squamous intraepithelial lesions in adolescents (loosely defined
as less than 21 years) as the one time to disaggregate cervical
intraepithelial neoplasia (CIN) 2 and CIN 3.

CIN 2 is more likely to regress in younger women and if it progresses
takes longer than in older women, thereby giving ample time to safely
follow CIN2. The caveat is that the patient understands that there is a
slightly increased risk of waiting and she needs to be compliant. The
exact interval may be derived iatrogenically from the nature of the
studies, but many of these young patients will clear the infection in
18-24 months.

Let's look at an example:

A 19 year old Gravida 0 Para 0 had an index liquid based pap smear with
atypical squamous cells of undetermined significance (ASCUS) and high
risk human papillomavirus (HPV**)** 6 months ago.

The patient received a colposcopy 2 months ago which showed a biopsy at
6 o\'clock biopsy that was normal and biopsy at 12 o\'clock that had CIN
1 and focal areas of CIN 2. Her endocervical curettage (ECC) was normal,
as was a liquid based pap smear.

As this patient is less than 21 years old, especially nulliparous young
women, she could be counseled about risks of treatment (including risks
of prematurity and possible need for another treatment later in life if
CIN recurs) and offer her the option of a repeat colposcopy and cytology
(both) at 4-6 month intervals for a year. If the lesion regresses, we
might do one more Pap in 6 months then return to annual screening. If
the CIN 2 persists for the year, we\'d encourage treatment. In many
cases, treatment can consist of cryotherapy, as LEEP has been associated
with prematurity (see Question #2 below)

Here are ACOG 2005 Recommendations

**Human Papillomavirus**

ACOG Practice Bulletin NUMBER 61, APRIL 2005

**Summary of Recommendations and Conclusions**

***The following recommendations are based on good and consistent
scientific evidence (Level A):***

-   Because HPV DNA testing is more sensitive than cervical cytology in
    detecting CIN 2 and CIN 3, women with negative concurrent test
    results can be reassured that their risk of unidentified CIN 2 and
    CIN 3 or cervical cancer is approximately 1 in 1,000.

-   Studies using combined HPV testing with cervical cytology have
    reported a negative predictive value for CIN 2 and CIN 3 of
    99--100%.

-   Human papillomavirus DNA testing is not recommended in women with
    LSIL, atypical squamous cells that cannot exclude high-grade
    squamous intraepithelial lesions, or atypical glandular cell
    cytology.

-   The triage of women with ASC-US cytology using reflex HPV DNA
    testing for high-risk types when liquid-based cytology was used at
    the time of the initial visit eliminates the need for a repeat
    office visit and is a more sensitive triage tool than repeat
    cytology while referring fewer women to colposcopy.

-   Women with high-risk HPV who have ASC-US or LSIL cytology but are
    not found to have CIN 2 or CIN 3 at their initial colposcopy have
    approximately a 10% risk of having CIN 2 or CIN 3 within 2 years.

***The following recommendations are based on limited or inconsistent
scientific evidence (Level B):***

-   Although evidence is lacking that condoms offer complete protection
    from HPV infection, condom use may reduce the risk of HPV-related
    disease, such as genital warts and cervical neoplasia.

-   Studies show that condoms may be effective in the clearance of HPV
    or HPV-associated lesions.

-   Use of a combination of cervical cytology and HPV DNA screening is
    appropriate for women aged 30 years and older. If this combination
    is used, women who receive negative results on both tests should be
    rescreened no more frequently than every 3 years.

-   Because of a similar risk of recurrence, no single treatment for
    external genital warts can be recommended over another.

***The following recommendations are based primarily on consensus and
expert opinion (Level C):***

-   Women older than 30 years with a negative cytology result who have
    high-risk HPV DNA positive test results should have both tests
    repeated in 6--12 months. Those with persistent high-risk HPV (on
    repeat testing) should undergo colposcopy regardless of the cytology
    result.

-   Human papillomavirus DNA testing could be used as a test of cure for
    women with CIN 2 or CIN 3 at 6--12 months following excision or
    ablation of the transformation zone. Those with high-risk HPV should
    be referred for colposcopy.

-   Treatment for genital warts should be guided by the preference of
    the patient and the experience of the heath care provider.

#### [OB/GYN CCC Editorial comment:]{.underline}

ACOG has provided a great deal of helpful information that should help
guide our screening for cervical cancer among Native women. I suggest
providers utilize the above Practice Bulletin and the American Society
for Colposcopy and Cervical Pathology Consensus Guidelines as
benchmarks. <http://www.asccp.org/consensus.shtml>

Indian Health providers and Native patients should be aware that there
are proprietary vendors aggressively marketing HPV tests directly to
patients under the guise of patient education and public health
information. Proprietary vendors can present an unrealistically
flattering portrayal of their products and may have different
motivations other than attaining the high possible health status of
Native women.

Human papillomavirus. ACOG Practice Bulletin No. 61. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2005; 105:905--18.

**ACOG non-Members**

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15802436>

**ACOG Member**

<http://www.acog.org/publications/educational_bulletins/pb061.cfm>

**American Society for Colposcopy and Cervical Pathology**

<http://www.asccp.org/>

**Patient Education available:**

**Helpful Human Papillomavirus (HPV) Infection**

**HPV Testing- Is it for me? ASCCP Patient Education brochure**

<http://asccp.org/pdfs/patient_edu/hpv_testing.pdf>

**ASCCP Patient Education site**

<http://asccp.org/patient_edu.shtml>

**CDC Human Papillomavirus (HPV) Infection** **resources**

<http://www.cdc.gov/std/hpv/default.htm>

**#2 What are some of the risks with LEEP?**

The study below further develops the literature base that supports that
LEEP is associated with adverse outcomes related to premature delivery
on subsequent pregnancies.

See also the CCC Corner 9/04 comments, re: Sadler 2004.

<http://www.ihs.gov/MedicalPrograms/MCH/M/OBGYN0904_HT.cfm#ob>

Patients should be counseled about these risks and providers should
fully outline alternative therapies, which may include careful
observation in many cases. The potential risks of LEEP on future
pregnancies is one more reason that low-grade CIN should followed
closely for a period of time instead of being immediately treated since
most low-grade CIN will spontaneously regress and will not need
treatment (ASCCP). If current therapy is deemed necessary, then
cryotherapy is often a reasonable alternative

**LEEP Treatment Increases Risk of Preterm Delivery in Future
Pregnancies**\
[OBJECTIVE]{.underline}: To estimate whether the loop electrosurgical
excision procedure (LEEP) is associated with an adverse effect on the
outcome of subsequent pregnancies.

[METHODS:]{.underline} A retrospective cohort study was performed. The
study group comprised women who had a LEEP in Halifax County between
1992 and 1999 and then had a subsequent singleton pregnancy of greater
than 20 weeks of gestation with delivery at the IWK Health Centre in
Halifax, Nova Scotia. The comparison group comprised women with no
history of cervical surgery who were matched for age, parity, smoking
status, and year of delivery. There were 571 women in each group. The
primary outcome was rate of preterm delivery at less than 37 weeks of
gestation. Secondary outcomes included delivery at less than 34 weeks
and various neonatal and maternal outcomes. The effect of specific LEEP
characteristics was analyzed separately. [RESULTS:]{.underline} Women
who had a LEEP were more likely to deliver preterm overall (7.9% versus
2.5%; odds ratio \[OR\] 3.50, 95% confidence interval \[CI\] 1.90-6.95;
P \< .001) and to deliver preterm after premature rupture of membranes
(PROM) (3.5% versus 0.9%; OR 4.10, 95% CI 1.48-14.09). The increase in
delivery at less than 34 weeks was not statistically significant (1.25%
versus 0.36%; OR 3.50, 95% CI 0.85-23.49; P = .12). Women with LEEP also
delivered more low birth weight (LBW) infants (5.4% versus 1.9%; OR
3.00, 95% CI 1.52-6.46; P = .003). There were no differences in other
neonatal or maternal outcomes. No association was found between the
characteristics of the LEEP, including depth, and the rate of preterm
delivery.

[CONCLUSION]{.underline}: Loop electrosurgical excision procedure is
associated with an increased risk of overall preterm delivery, preterm
delivery after PROM, and LBW infants in subsequent pregnancies at
greater than 20 weeks of gestation. Women who are considering future
pregnancies should be counseled about these risks during informed
consent for LEEP.

LEVEL OF EVIDENCE: II-2.

Samson SL et al The effect of loop electrosurgical excision procedure on
future pregnancy outcome.Obstet Gynecol. 2005 Feb;105(2):325-32.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=15684160&dopt=Abstract>

**Other resources re: LEEP:**

**ACOG: LEEP Treatment Increases Risk of Preterm Delivery in Future
Pregnancies**

<https://www.acog.com/from_home/publications/press_releases/nr01-31-05-2.cfm>

**CCC Corner 9/04 comments, re: Sadler 2004**

<http://www.ihs.gov/MedicalPrograms/MCH/M/OBGYN0904_HT.cfm#ob>

Sadler L, et al Treatment for cervical intraepithelial neoplasia and
risk of preterm delivery. JAMA. 2004 May 5;291(17):2100-6.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15126438>

**Clinical uses of human papillomavirus (HPV) DNA Self Assessment
Booklet: ASCCP**

[http://www.asccp.org/bookstore.shtml#](http://www.asccp.org/bookstore.shtml)

<http://www.asccp.org/edu/hpv_testing.shtml>