12/11/05 njm

**Q. Is an abnormal Pap smear an** **effect of DES exposure in adult
daughters?**

A. There is an increase risk of HGSIL in DES-exposed daughters. See
details

I was DES exposed in both my mother's first trimester and second
trimester.  I had abnormal Paps for many years and then they were fine
for all the intervening years. Recently I had an abnormal (low-grade
lesion) Pap and had a colposcopy yesterday.

Is there some reliable data/information about the effects of DES
exposure in adult daughters?

**DES: Cervical squamous intraepithelial lesions and cancer** --- Two
studies have found an approximately two-fold increase in risk of
high-grade squamous intraepithelial lesions in DES-exposed daughters
(Robboy, Hatch). The excess risk may be due to an increase in the size
of the cervical transformation zone, leading to greater susceptibility
to HPV infection.  A study from the Netherlands found that the
prevalence of cervical cancer was approximately three-fold higher than
expected among DES-exposed daughters, but the study was limited by small
numbers and lack of documentation of DES exposure (Verloop). Although
the relationship of DES and squamous cell disease of the cervix is
somewhat uncertain, the National Cancer Institute recommends that DES
exposed women have annual cervical cancer screening throughout their
lives. (NCI)

[References:]{.underline}

Robboy SJ; Noller KL; O\'Brien P; Kaufman RH; Townsend D; Barnes AB;
Gundersen J; Lawrence WD; Bergstrahl E; McGorray S; et al. Increased
incidence of cervical and vaginal dysplasia in 3,980
diethylstilbestrol-exposed young women. Experience of the National
Collaborative Diethylstilbestrol Adenosis Project.  JAMA 1984 Dec
7;252(21):2979-83.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6502858&query_hl=6>

The incidence rates of dysplasia and carcinoma in situ (CIS) of the
cervix and vagina were determined in 3,980 young women exposed
prenatally to diethylstilbestrol. Strict criteria were developed to
minimize selection bias among the subset of 744 pairs of matched exposed
and unexposed (control) cohort participants, all of whom were identified
through review of prenatal obstetrical records. A high degree of
compliance was achieved throughout the seven-year study period since in
each group about 90% of the women remained as active participants, kept
77% of the annual anniversary examinations, and had separate
Papanicolaou smears of the cervix and vagina performed in 99% of the
anniversary examinations. The incidence rate for dysplasia and CIS was
significantly higher in the women exposed to diethylstilbestrol than in
those not exposed in the matched cohort (15.7 v 7.9 cases per 1,000
person-years of follow-up). The rates were higher in the exposed women
if squamous metaplasia extended to the outer half of the cervix or onto
the vagina. In other respects, the matched cohorts were strikingly
similar.\
\
Hatch EE; Herbst AL; Hoover RN; Noller KL; Adam E; Kaufman RH; Palmer
JR; Titus-Ernstoff L; Hyer M; Hartge P; Robboy SJ  Incidence of squamous
neoplasia of the cervix and vagina in women exposed prenatally to
diethylstilbestrol (United States). Cancer Causes Control 2001
Nov;12(9):837-45.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11714112&query_hl=3>\
\
OBJECTIVES: Women exposed prenatally to diethylstibestrol (DES) have an
excess risk of clear-cell adenocarcinoma of the vagina and cervix, but
the effect on the incidence of squamous neoplasia is uncertain. The
purpose of the current study was to evaluate the long-term risk of
developing high-grade squamous neoplasia of the genital tract among
women exposed prenatally to DES. METHODS: A cohort comprising 3,899
DES-exposed and 1,374 unexposed daughters was followed for 13 years
(1982 1995) for pathology-confirmed diagnoses of high-grade squamous
intraepithelial neoplasia (HSIL) of the genital tract. Poisson
regression analysis was used to compute relative risks (RR) and 95%
confidence intervals (95% CI), adjusting for age, calendar year, and
other covariates. RESULTS: The RR (95% CI) among DES-exposed versus
unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8).
Adjustment for screening history estimated by the number of years since
the last Pap smear had little effect. Risk estimates were higher with
earlier intrauterine exposure; the RR (95% CI) for exposure within 7
weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of
invasive squamous cervical cancer occurred in total, precluding separate
analysis. CONCLUSIONS: The findings support an association between
in-utero DES exposure and high-grade squamous neoplasia, although a role
for more intensive screening among DES-exposed women in the production
of this excess could not be completely ruled out.

**Other References:**

**Outcome of diethylstilbestrol exposed individuals, UpToDate**

<http://www.uptodateonline.com/application/topic.asp?file=gen_gyne/17625&type=A&selectedTitle=1~16>

Verloop, J, Rookus, MA, van Leeuwen, FE. Prevalence of gynecologic
cancer in women exposed to diethylstilbestrol in utero. N Engl J Med
2000; 342:1838.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10866558&query_hl=1>

National Cancer Institute. DES: Questions and answers. Cancer Facts.
[cis.nci.nih.gov/fact/3_4.htm]{.underline}

ASCCP Consensus Guidelines

<http://www.asccp.org/pdfs/consensus/algorithms.pdf>

Wright TC et al 2001 Consensus Guidelines for the management of women
with cervical intraepithelial neoplasia. Am J Obstet Gynecol 2003
Jul;189(1):295-304.
<http://www2.us.elsevierhealth.com/inst/serve?action=searchDB&searchDBfor=art&artType=abs&id=amob03633&nav=abs>

or

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12861176&dopt=MEDLINE>

or

<http://www2.us.elsevierhealth.com/inst/serve?action=searchDB&searchDBfor=art&artType=fullfree&id=amob03633>