                   AIDS INFORMATION NEWSLETTER
                   Michael Howe, MSLS, Editor
                     AIDS Information Center
                VA Medical Center, San Francisco
                     (415) 221-4810 ext 3305
                         March 22, 1996

                Opportunistic Infections (Part XXII)
                         Cervical Cancer

(Excerpt from:  Centers for Disease Control and Prevention. 1993
Revised Classification system for HIV infection and expanded
surveillance case definition for AIDS among adolescents and adults. 
MMWR 1992;41(No.RR-17):[Inclusive page numbers].)

     Several studies have found an increased prevalence of cervical
dysplasia, a precursor lesion for cervical cancer, among HIV-
infected women (60, 61). In a study of 310 HIV-infected women
attending methadone maintenance and sexually transmitted disease
clinics in New York City and Newark, New Jersey, cervical dysplasia
was confirmed by biopsy and/or colposcopy in approximately 22%, a
prevalence rate 10 times greater than that found among women
attending family planning clinics in the United States (Wright TC,
personal communication; 62). Several studies have documented that
a higher prevalence of cervical dysplasia among HIV-infected women
is associated with greater immunosuppression (Wright TC, personal
communication; 61,63).  In addition, HIV infection may adversely
affect the clinical course and treatment of cervical dysplasia and
cancer (64-69).
     Invasive cervical cancer is a more appropriate AIDS-indicator
disease than is either cervical dysplasia or carcinoma in situ
because these latter cervical lesions are common and frequently do
not progress to invasive disease (70). Also, cervical dysplasia or
carcinoma in situ among women with severe cervicovaginal
infections, which are common in HIV-infected women, can be
difficult to diagnose. In contrast, the diagnosis of invasive
cervical cancer is generally unequivocal.
     Invasive cervical cancer is preventable by the proper
recognition and treatment of cervical dysplasia. Thus, the
occurrence of invasive cervical cancer among all women--including
those who are HIV-infected--represents missed opportunities for
disease prevention.  The addition of invasive cervical cancer to
the list of AIDS-indicator diseases emphasizes the importance of
integrating gynecologic care into medical services for HIV-infected
women.

References

60.  Laga M, Icenogle JP, Marsella R, et al. Genital papillomavirus
     infection and cervical dysplasia--opportunistic complications
     of HIV infection. Int J Cancer 1992;50:45-8.

61.  Schafer A, Friedmann W, Mielke M, Schwartlander B, Koch MA.
     The increased frequency of cervical dysplasia-neoplasia in
     women infected with the human immunodeficiency virus is
     related to the degree of immunosuppression. Am J Obstet
     Gynecol 1991;164:593-9.

62.  Sadeghi SB, Sadeghi A, Robboy SJ. Prevalence of dysplasia and
     cancer of the cervix in a nationwide Planned Parenthood
     population.  Cancer 1988;61:2359-61.

63.  Feingold AR, Vermund SH, Burk RD, et al. Cervical cytologic
     abnormalities and papillomavirus in women infected with human
     immunodeficiency virus. J Acquir Immune Defic Syndr
     1990;3:896-903.

64.  Maiman M, Fruchter RG, Serur E, Remy JC, Feuer G, Boyce J.
     man immunodeficiency virus infection and cervical neoplasia.
     Gynecol Oncol 1990;38:377-82.

65.  Klein RS, Adachi A, Fleming I, Ho GYF, Burk R. A prospective
     study of genital neoplasia and human papillomavirus (HPV) in
     HIV-infected women (abstract). Vol.1. Presented at the VIII
     International Conference on AIDS/III STD World Congress,
     Amsterdam, The Netherlands, July 19-24, 1992.

66.  Fruchter R, Maiman M, Serur E, Cuthill S. Cervical
     intraepithelial neoplasia in HIV infected women (abstract). 
     Vol.1.  Presented at the VIII International Conference on
     AIDS/III STD World Congress, Amsterdam, The Netherlands, July
     19-24, 1992.

67.  Richart RM, Wright TC. Controversies and the management of
     low-grade cervical intraepithelial neoplasia. Cancer (in
     press).

68.  Rellihan MA, Dooley DP, Burke TW, Berkland ME, Longfield RN. 
     Rapidly progressing cervical cancer in a patient with human
     immunodeficiency virus infection. Gynecol Oncol 1990;
     36:435-8.

69.  Schwartz LB, Carcangiu ML, Bradham L, Schwartz PE. Rapidly
     progressive squamous carcinoma of the cervix coexisting with
     human immunodeficiency virus infection: clinical opinion.
     Gynecol Oncol 1991;41:255-8.

70.  Richart RM. Cervical intraepithelial neoplasia: a review. 
     In: Sommers SC, ed. Pathology annual, 1973. New
     York:Appleton-Century- Crofts, 1973:301-28.

                    Invasive Cervical Cancer
                  CDC Training Bulletin Excerpt

     Question:  Now that invasive cervical cancer has been added
to the list of indicator illnesses for AIDS, can CDC recommend how
often women who are HIV+ should have a pap smear?

     Answer:  Recommendations for the medical management of
HIV-infected women is not dependent on the addition of diseases,
such as invasive cervical cancer, to the CDC AIDS case surveillance
definition.  The 1993 expanded AIDS case definition did not result
in the reporting of many AIDS cases among women with a presenting
diagnosis of invasive cervical cancer.  PCP is still the leading
AIDS-defining diagnosis among women reported with AIDS through June
1993.  The November 30, 1990, edition of the MMWR contained a 1988
consensus recommendation from several organizations concerning how
frequently women with and at risk for HIV infection should have Pap
smears.  Although personal physicians must make this decision based
on risk factors for cervical cancer, the recommendation states that
HIV-infected women should have a Pap smear annually.  The American
College of Obstetrics and Gynecology reiterated this information
in their 1992 recommendations. (Centers for Disease Control and
Prevention.  Training Bulletin #62.  August 23, 1993.)

         Cervical Cancer Screening for Women Who Attend
            STD Clinics or Who Have a History of STDs

(Centers for Disease Control and Prevention. 1993 Sexually
Transmitted Diseases Treatment Guidelines. 1993 Sept;42(No. RR-
14):[pages inclusive].)

     Women who have a history of STDs are at increased risk for
cervical cancer, and women attending STD clinics may have
additional characteristics that place them at even higher risk. 
Prevalence studies have found that precursor lesions for cervical
cancer occur approximately five times more often among women
attending STD clinics than among women attending family planning
clinics.
     The Pap smear (cervical smear) is an effective and relatively
low-cost screening test for invasive cervical cancer and squamous
intraepithelial lesions (SIL)*, the precursors of cervical cancer. 
The screening guidelines of both the American college of
Obstetricians and Gynecologists and the American Cancer Society
recommend annual Pap smears for sexually active women.  Although
these guidelines take the position that Pap smears can be obtained
less frequently in some situations, women who attend STD clinics
or who have a history of STDs should be screened annually because
of their increased risk for cervical cancer.  Moreover, reports
from STD clinics indicate that many women do not understand the
purpose or importance of Pap smears, and many women who have had
a pelvic examination believe they have had a Pap smear when they
actually have not.

Recommendations

     Whenever a woman has a pelvic examination for STD screening,
the health-care provider should inquire about the result of her
last Pap smear and should discuss the following information with
the patient:

  o  Purpose and importance of the Pap smear,

  o  Whether a Pap smear was obtained during the clinic visit,

  o  Need for a Pap smear each year,

  o  Names of local providers or referral clinics that can obtain
     Pap smears and adequately follow up results (if a Pap smear
     was not obtained during this examination).

     If a woman has not had a Pap smear during the previous 12
months, a Pap smear should be obtained as part of the routine
pelvic examination in most situations.  Health-care providers
should be aware that, after a pelvic examination, many women may
believe they had a Pap smear when they actually have not, and
therefore may report they have had a recent Pap sear.
     In STD clinics, a Pap smear should be obtained during the
routine clinical evaluation of women who have not had a documented
normal smear within the past 12 months.
     A woman may benefit from receiving printed information about
Pap smears and a report containing a statement that a Pap smear
was obtained during her clinic visit.  Whenever possible, a copy
of the Pap smear result should be sent to the patient for her
records.

FOLLOW-UP

     If a Pap smear shows severe inflammation with reactive
cellular changes, the women should be advised to have another Pap
smear within 3 months.  If possible, underlying infection should
be treated before the repeat Pap smear is obtained.
     If a Pap smear shows either SIL (or equivalent) or atypical
squamous cells of undetermined significance (ASCUS), the woman
should be notified promptly and appropriate follow-up initiated.
     Appropriate follow-up of Pap smears showing a high-grade SIL
(or equivalent) on Pap smears should always include referral to a
health-care provider who has the capacity to provide a colposcopic
examination of the lower genital tract and, if indicated,
colposcopically directed biopsies.  Because clinical follow-up of
abnormal Pap smears with colposcopy and biopsy is beyond the scope
of many public clinics, including most STD clinics, in most
situations women with Pap smears demonstrating these abnormalities
will need to be referred to other local providers or clinics. 
Women with either a low-grade SIL or ASCUS also need similar
follow-up, although some experts believe that, in some situations,
a repeat Pap smear may be a satisfactory alternative to referral
for colposcopy and biopsy.

OTHER MANAGEMENT CONSIDERATIONS

     Other considerations in performing Pap smears are the
following:

  o  The Pap smear is not an effective screening test for STDs;

  o  If a woman in menstruating, a Pap smear should be postponed
     and the woman should be advised to have a Pap smear at the
     earliest opportunity;

  o  If a woman has an obvious severe cervicitis, the Pap smear
     may be deferred until after antibiotic therapy has been
     completed to obtain an optimum smear;

  o  A woman with external genital warts does not require Pap
     smears more frequently than a woman without warts, unless
     otherwise indicated.

SPECIAL CONSIDERATIONS

PREGNANCY

     Women who are pregnant should have a Pap smear as part of
routine prenatal care.  A cytobrush may be used for obtaining Pap
smears from pregnant women, although care should be taken not to
disrupt the mucous plug.

HIV INFECTION

     Recent studies have documented an increased prevalence of SIL
among women infected with HIV.  Also, HIV may hasten the
progression of precursor lesions to invasive cervical cancer;
however, evidence supporting such a progression is limited.  The
following provisional recommendations for pap smear screening among
HIV-infected women are based partially on consultation with experts
in the care and management of cervical cancer and HIV infection
among women.
     These provisional recommendations may be altered in the future
as more information regarding cervical disease among HIV-infected
women becomes available:

  o  Women who are HIV-infected should be advised to have a
     comprehensive gynecologic examination, including a Pap smear,
     as part of their initial medical evaluation.

  o  If initial Pap smear results are within normal limits, at
     least one additional Pap smear should be obtained in
     approximately 6 months to rule out the possibility of false-
     negative results on the initial Pap smear.  If the repeat Pap
     smear is normal, HIV-infected women should be advised to have
     a Pap smear obtained annually.

  o  If the initial or follow-up Pap smear shows severe
     inflammation with reactive squamous cellular changes, another
     Pap smear should be collected within 3 months.

  o  If the initial or follow-up Pap smear shows SIL (or
     equivalent) or ASCUS, the woman should be referred for a
     colposcopic examination of the lower genital tract and, if
     indicated, colposcopically directed biopsies.

HIV infection is not an indication for colposcopy among women with
normal Pap smears.

*The 1988 Bethesda System for Reporting Cervical/Vaginal Cytologic
Diagnoses introduced the new terms low-grade squamous
intraepithelial lesion (SIL) and high-grade SIL.  Low-grad SIL
encompasses cellular changes associated with HPV and mild
dysplasia/cervical intraepithelial neoplasia 1 (CIN 1).  High-
grade SIL includes moderate dysplasia/CIN 2, severe dysplasia/CIN
3, and carcinoma in situ (CIS)/CIN 3 (16).

[Note:  For an overview of the management of HIV disease in women,
see:  Wofsy CB. Padian NS. Cohen JB. et al. Management of HIV
Disease in Women. In: Volberding P. Jacobson MA., eds. AIDS
Clinical Care 1992. New York: Marcel Dekker, Inc., 1992:301-328.]


                          Editor's Note

  More information about women and HIV infection is included in the
AIDS Information Newsletter series, Women and HIV Infection.  This
twenty-five part series was transmitted between June 3, 1994 and
May 5, 1995 to all VA medical centers.  The series (as well as
other newsletter series) is available on the internet.

                         Internet Access

  The AIDS Information Newsletter is emailed directly to the
National Institute of Allergy and Infectious Diseases gopher site
(gopher.niaid.nih.gov).  Menu path is:  2. AIDS Related
Information; 11. VA AIDS Information Newsletter.  URL is:
gopher://gopher.niaid.nih.gov/11/aids/vaain
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