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Sexually Transmitted Diseases (STD) Human Papillomavirus Infection (Genital Warts)

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Author:    Julia Tortorice (RN, MBA, MSN, NEA-BC, CPHQ)

Objectives

After completing the course, the learner will be able to:

 

Identify signs and symptoms of HPV.

 

Identify recommended treatment, follow-up and partner referral.

 

Identify special issues with HPV in pregnant patient, infants and immunocompromised patients.

Genital Warts

More than 20 types of Human Papillomavirus Infection (HPV) can infect the genital tract. Most HPV infections are asymptomatic, subclinical, or unrecognized. Visible genital warts usually are caused by HPV types 6 or 11. Other HPV types in the anogenital region (i.e., types 16, 18, 31, 33, and 35) have been strongly associated with cervical dysplasia. Diagnosis of genital warts can be confirmed by biopsy, although biopsy is rarely needed (e.g., if the diagnosis is uncertain; the lesions do not respond to standard therapy; the disease worsens during therapy; the patient is immunocompromised; or warts are pigmented, indurated, fixed, and ulcerated). No data support the use of type-specific HPV nucleic acid tests in the routine diagnosis or management of visible genital warts.

 

HPV types 6 and 11 also can cause warts on the uterine cervix and in the vagina, urethra, and anus; these warts are sometimes symptomatic. Intra-anal warts are seen predominately in patients who have had receptive anal intercourse; these warts are distinct from perianal warts, which can occur in men and women who do not have a history of anal sex. Other than the genital area, these HPV types have been associated with conjunctival, nasal, oral, and laryngeal warts. HPV types 6 and 11 are associated rarely with invasive squamous cell carcinoma of the external genitalia. Depending on the size and anatomic locations, genital warts can be painful, friable, and/or pruritic.

 

HPV types 16, 18, 31, 33, and 35 are found occasionally in visible genital warts and have been associated with external genital (i.e., vulvar, penile, and anal) squamous intraepithelial neoplasia (i.e., squamous cell carcinoma in situ, bowenoid papulosis, Erythroplasia of Queyrat, or Bowen's disease of the genitalia). These HPV types have been associated with vaginal, anal, and cervical intraepithelial dysplasia and squamous cell carcinoma. Patients who have visible genital warts can be infected simultaneously with multiple HPV types.

 

Treatment

 

The primary goal of treating visible genital warts is the removal of symptomatic warts. Treatment can induce wart-free periods in most patients. Genital warts often are asymptomatic. No evidence indicates that currently available treatments eradicate or affect the natural history of HPV infection. The removal of warts may or may not decrease infectivity. If left untreated, visible genital warts may resolve on their own, remain unchanged, or increase in size or number. No evidence indicates that treatment of visible warts affects the development of cervical cancer.

 

Regimens

 

Treatment of genital warts should be guided by the preference of the patient, the available resources, and the experience of the health-care provider. None of the available treatments is superior to other treatments, and no single treatment is ideal for all patients or all warts.

 

The available treatments for visible genital warts are patient-applied therapies (i.e., podofilox and imiquimod) and provider-administered therapies (i.e., cryotherapy, podophyllin resin, trichloroacetic acid {TCA}, bichloroacetic acid {BCA}, interferon, and surgery). Most patients have from one to 10 genital warts, with a total wart area of 0.5-1.0 cm2, that are responsive to most treatment modalities. Factors that might influence selection of treatment include wart size, wart number, anatomic site of wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects, and provider experience. Having a treatment plan or protocol is important, because many patients will require a course of therapy rather than a single treatment. In general, warts located on moist surfaces and/or in intertriginous areas respond better to topical treatment (e.g., TCA, podophyllin, podofilox, and imiquimod) than do warts on drier surfaces.

 

The treatment modality should be changed if a patient has not improved substantially after three provider-administered treatments or if warts have not completely cleared after six treatments. The risk-benefit ratio of treatment should be evaluated throughout the course of therapy to avoid overtreatment. Providers should be knowledgeable about, and have available to them, at least one patient-applied and one provider-administered treatment.

 

Complications rarely occur if treatments for warts are employed properly. Patients should be warned that scarring in the form of persistent hypopigmentation or hyperpigmentation is common with ablative modalities. Depressed or hypertrophic scars are rare but can occur, especially if the patient has had insufficient time to heal between treatments. Treatment can result rarely in disabling chronic pain syndromes (e.g., vulvodynia or hyperesthesia of the treatment site).

 

External Genital Warts, Recommended Treatments

Patient-Applied:

Podofilox 0.5% solution or gel. Patients may apply podofilox solution with a cotton swab, or podofilox gel with a finger, to visible genital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle may be repeated as necessary for a total of four cycles. The total wart area treated should not exceed 10 cm2, and a total volume of podofilox should not exceed 0.5 mL per day. If possible, the health-care provider should apply the initial treatment to demonstrate the proper application technique and identify which warts should be treated. The safety of podofilox during pregnancy has not been established. OR Imiquimod 5% cream. Patients should apply imiquimod cream with a finger at bedtime, three times a week for as long as 16 weeks. The treatment area should be washed with mild soap and water 6-10 hours after the application. Many patients may be clear of warts by 8-10 weeks or sooner. The safety of imiquimod during pregnancy has not been established.

 

Provider-Administered:

Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1 to 2 weeks. OR Podophyllin resin 10%-25% in compound tincture of benzoin. A small amount should be applied to each wart and allowed to air dry. To avoid the possibility of complications associated with systemic absorption and toxicity, some experts recommend that application be limited to less than or equal to 0.5 mL of podophyllin or less than or equal to 10 cm2 of warts per session. Some experts suggest that the preparation should be thoroughly washed off 1-4 hours after application to reduce local irritation. Repeat weekly if necessary. The safety of podophyllin during pregnancy has not been established. OR TCA or BCA 80%-90%. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.

Externam Genital Warts, Alternative Treatments

Intralesional interferon, OR Laser surgery.

 

For patient-applied treatments, patients must be able to identify and reach warts to be treated. Podofilox 0.5% solution or gel is relatively inexpensive, easy to use, safe, and self-applied by patients. Podofilox is an antimitotic drug that results in destruction of warts. Most patients experience mild/moderate pain or local irritation after treatment. Imiquimod is a topically active immune enhancer that stimulates production of interferon and other cytokines. Before wart resolution, local inflammatory reactions are common; these reactions usually are mild to moderate.

 

Cryotherapy, which requires the use of basic equipment, destroys warts by thermal-induced cytolysis. Its major drawback is that proper use requires substantial training, without which warts are frequently overtreated or undertreated, resulting in poor efficacy or increased likelihood of complications. Pain after application of the liquid nitrogen, followed by necrosis and sometimes blistering, are not unusual. Although local anesthesia (topical or injected) is not used routinely, its use facilitates treatment if there are many warts or if the area of warts is large.

 

Podophyllin resin contains a number of compounds, including the podophyllin lignans that are antimitotic. The resin is most frequently compounded at 10%-25% in tincture of benzoin. However, podophyllin resin preparations differ in the concentration of active components and contaminants. The shelf life and stability of podophyllin preparations are unknown. It is important to apply a thin layer of podophyllin resin to the warts and allow it to air dry before the treated area comes into contact with clothing. Overapplication or failure to air dry can result in local irritation caused by spread of the compound to adjacent areas.

Both TCA and BCA are caustic agents that destroy warts by chemical coagulation of the proteins. Although these preparations are widely used, they have not been investigated thoroughly. TCA solutions have a low viscosity comparable to water and can spread rapidly if applied excessively, thus damaging adjacent normal tissue. Both TCA and BCA should be applied sparingly and allowed to dry before the patient sits or stands. If pain is intense, the acid can be neutralized with soap or sodium bicarbonate (i.e., baking soda).

Surgical removal of warts has an advantage over other treatment modalities in that it renders the patient wart-free, usually with a single visit. However, substantial clinical training, additional equipment, and a longer office visit are required. Once local anesthesia is achieved, the visible genital warts can be physically destroyed by electrosurgery, in which case no additional hemostasis is required. Alternatively, the warts can be removed either by tangential excision with a pair of fine scissors or a scalpel or by curettage. Because most warts are exophytic, this can be accomplished with a resulting wound that only extends into the upper dermis. Hemostasis can be achieved with an electrosurgical unit or a chemical styptic (e.g., an aluminum chloride solution). Suturing is neither required nor indicated in most cases when surgical removal is done properly. Surgery is most beneficial for patients who have a large number or area of genital warts. Carbon dioxide laser and surgery may be useful in the management of extensive warts or intraurethral warts, particularly for those patients who have not responded to other treatments.

 

Interferons, either natural or recombinant, used for the treatment of genital warts have been administered systemically (i.e., subcutaneously at a distant site or IM) and intralesionally (i.e., injected into the warts). Systemic interferon is not effective. The efficacy and recurrence rates of intralesional interferon are comparable to other treatment modalities. Interferon is believed to be effective because of antiviral and/or immunostimulating effects. However, interferon therapy is not recommended for routine use because of inconvenient routes of administration, frequent office visits, and the association between its use and a high frequency of systemic adverse effects.

 

Because of the shortcomings of available treatments, some clinics employ combination therapy (i.e., the simultaneous use of two or more modalities on the same wart at the same time). Most experts believe that combining modalities does not increase efficacy but may increase complications.

Cervical Warts

 

For women who have exophytic cervical warts, high-grade squamous intraepithelial lesions (SIL) must be excluded before treatment is begun. Management of exophytic cervical warts should include consultation with an expert.

 

Vaginal Warts

 

Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation. OR TCA or BCA 80%-90% applied only to warts. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Podophyllin 10%-25% in compound tincture of benzoin applied to a treated area that must be dry before the speculum is removed. Treat with less than or equal to 2 cm2 per session. Repeat application at weekly intervals. Because of concern about potential systemic absorption, some experts caution against vaginal application of podophyllin. The safety of podophyllin during pregnancy has not been established.

 

Urethral Meatus Warts

 

Cryotherapy with liquid nitrogen, OR Podophyllin 10%-25% in compound tincture of benzoin. The treatment area must be dry before contact with normal mucosa. Podophyllin must be applied weekly if necessary. The safety of podophyllin during pregnancy has not been established.

 

Anal Warts

 

Cryotherapy with liquid nitrogen. OR TCA or BCA 80%-90% applied to warts. Apply a small amount only to warts and allow to dry, at which time a white "frosting" develops; powder with talc or sodium bicarbonate (i.e., baking soda) to remove unreacted acid if an excess amount is applied. Repeat weekly if necessary. OR Surgical removal.

Note: Management of warts on rectal mucosa should be referred to an expert.

 

Oral Warts

 

Cryotherapy with liquid nitrogen, OR Surgical removal.

 

Follow-Up

 

After visible genital warts have cleared, a follow-up evaluation is not mandatory. Patients should be cautioned to watch for recurrences, which occur most frequently during the first 3 months. Because the sensitivity and specificity of self-diagnosis of genital warts is unknown, patients concerned about recurrences should be offered a follow-up evaluation 3 months after treatment. Earlier follow-up visits also may be useful a) to document a wart-free state, b) to monitor for or treat complications of therapy, and c) to provide the opportunity for patient education and counseling. Women should be counseled regarding the need for regular cytologic screening as recommended for women without genital warts. The presence of genital warts is not an indication for cervical colposcopy.

 

Management of Sex Partners

 

Examination of sex partners is not necessary for the management of genital warts because the role of reinfection is probably minimal and, in the absence of curative therapy, treatment to reduce transmission is not realistic. However, because self- or partner-examination has not been evaluated as a diagnostic method for genital warts, sex partners of patients who have genital warts may benefit from examination to assess the presence of genital warts and other STDs. Sex partners also might benefit from counseling about the implications of having a partner who has genital warts. Because treatment of genital warts probably does not eliminate the HPV infection, patients and sex partners should be cautioned that the patient might remain infectious even though the warts are gone. The use of condoms may reduce, but does not eliminate, the risk for transmission to uninfected partners. Female sex partners of patients who have genital warts should be reminded that cytologic screening for cervical cancer is recommended for all sexually active women.

 

Special Considerations

Special Considerations

 

Pregnancy

 

Imiquimod, podophyllin, and podofilox should not be used during pregnancy. Because genital warts can proliferate and become friable during pregnancy, many experts advocate their removal during pregnancy. HPV types 6 and 11 can cause laryngeal papillomatosis in infants and children. The route of transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood. The preventive value of cesarean section is unknown; thus, cesarean delivery should not be performed solely to prevent transmission of HPV infection to the newborn. In rare instances, cesarean delivery may be indicated for women with genital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding.

 

Immunosuppressed Patients

 

Persons who are immunosuppressed because of HIV or other reasons may not respond as well as immunocompetent persons to therapy for genital warts, and they may have more frequent recurrences after treatment. Squamous cell carcinomas arising in or resembling genital warts might occur more frequently among immunosuppressed persons, requiring more frequent biopsy for confirmation of diagnosis.

 

Squamous Cell Carcinoma in situ

 

Patients in whom squamous cell carcinoma in situ of the genitalia is diagnosed should be referred to an expert for treatment. Ablative modalities usually are effective, but careful follow-up is important. The risk for these lesions leading to invasive squamous cell carcinoma of the external genitalia in immunocompetent patients is unknown but is probably low. Female partners of patients who have squamous cell carcinoma in situ are at high risk for cervical abnormalities.

 

Subclinical Genital HPV Infection (Without Exophytic Warts)

 

Subclinical genital HPV infection occurs more frequently than visible genital warts among both men and women. Infection often is indirectly diagnosed on the cervix by Pap smear, colposcopy, or biopsy and on the penis, vulva, and other genital skin by the appearance of white areas after application of acetic acid. However, the routine use of acetic acid soaks and examination with light and magnification, as a screening test, to detect "subclinical" or "acetowhite" genital warts is not recommended. Acetowhitening is not a specific test for HPV infection. Thus, in populations at low risk for this infection, many false-positives may be detected when this test is used for screening. The specificity and sensitivity of this procedure has not been defined. In special situations, experienced clinicians find this test useful for identification of flat genital warts.

 

A definitive diagnosis of HPV infection depends on detection of viral nucleic acid (DNA or RNA) or capsid protein. Pap smear diagnosis of HPV does not always correlate with detection of HPV DNA in cervical cells. Cell changes attributed to HPV in the cervix are similar to those of mild dysplasia and often regress spontaneously without treatment. Tests that detect several types of HPV DNA or RNA in cells scraped from the cervix are available, but the clinical utility of these tests for managing patients is unclear. Management decisions should not be made on the basis of HPV tests. Screening for subclinical genital HPV infection using DNA or RNA tests or acetic acid is not recommended.

 

Treatment

 

In the absence of coexistent dysplasia, treatment is not recommended for subclinical genital HPV infection diagnosed by Pap smear, colposcopy, biopsy, acetic acid soaking of genital skin or mucous membranes, or the detection of HPV (DNA or RNA). The diagnosis of subclinical genital HPV infection is often questionable, and no therapy has been identified to eradicate infection. HPV has been demonstrated in adjacent tissue after laser treatment of HPV-associated dysplasia and after attempts to eliminate subclinical HPV by extensive laser vaporization of the anogenital area. In the presence of coexistent dysplasia, management should be based on the grade of dysplasia.

 

Management of Sex Partners

 

Examination of sex partners is unnecessary. Most sex partners of infected patients probably are already infected subclinically with HPV. No practical screening tests for subclinical infection are available. The use of condoms may reduce transmission to sex partners who are likely to be uninfected (e.g., new partners); however, the period of communicability is unknown. Whether patients who have subclinical HPV infection are as contagious as patients who have exophytic warts is unknown.

CERVICAL CANCER SCREENING FOR WOMEN WHO ATTEND STD CLINICS OR HAVE A HISTORY OF STDs

Women who have a history of STD are at increased risk for cervical cancer, and women attending STD clinics may have other risk factors that place them at even greater risk. Prevalence studies have determined that precursor lesions for cervical cancer occur about five times more frequently among women attending STD clinics than among women attending family planning clinics.

The Pap smear (i.e., cervical smear) is an effective and relatively low-cost screening test for invasive cervical cancer and SIL, * the precursors of cervical cancer. Both ACOG and the American Cancer Society (ACS) recommend annual Pap smears for all sexually active women. Although these guidelines take the position that Pap smears can be obtained less frequently in some situations, women with a history of STDs may need more frequent screening because of their increased risk for cervical cancer. Moreover, surveys of women attending STD clinics indicate that many women do not understand the purpose or importance of Pap smears, and almost half of the women who have had a pelvic examination erroneously believe they have had a Pap smear when they actually have not. --------------------

·         The 1988 Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses introduced the terms "low-grade SIL" and "high-grade SIL" (27). Low-grade 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/CIN 3.

Recommendations

At the time of a pelvic examination for STD screening, the health-care provider should inquire about the result of the patient's last Pap smear and discuss the following information with the patient:

·         The purpose and importance of a Pap smear;

·         Whether a Pap smear was obtained during the clinic visit;

·         The need for an annual Pap smear; and

·         The names of local providers or referral clinics that can obtain Pap smears and adequately follow up results (i.e., 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. Health-care providers should be aware that, after a pelvic examination, many women believe they have had a Pap smear when they actually have not, and thus may report having had a recent Pap smear. Therefore, in STD clinics, a Pap smear should be strongly considered during the routine clinical evaluation of women who have not had a normal Pap smear within the preceding 12 months that is documented within the clinic record or linked-system record.

 

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. If possible, a copy of the Pap smear result should be provided to the patient for her records.

 

Follow-Up

 

Clinics and health-care providers who provide Pap smear screening services are encouraged to use cytopathology laboratories that report results using the Bethesda System of classification. If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by the National Cancer Institute Consensus Panel and briefly summarized below (27). Appropriate follow-up of Pap smears showing a high-grade SIL always includes referral to a clinician who has the capacity to provide a colposcopic examination of the lower genital tract and, if indicated, colposcopically directed biopsies. For a Pap smear showing low-grade SIL or atypical squamous cells of undetermined significance (ASCUS), follow-up without colposcopy may be acceptable in circumstances when the diagnosis is not qualified further or the cytopathologist favors a reactive process. In general, this would involve repeated Pap smears every 4-6 months for 2 years until the results of three consecutive smears have been negative. If repeated smears show persistent abnormalities, colposcopy and directed biopsy are indicated for low-grade SIL and should be considered for ASCUS. Women with a diagnosis of unqualified ASCUS associated with severe inflammation should at least be reevaluated with a repeat Pap smear after 2-3 months, then repeated Pap smears every 4-6 months for 2 years until the results of three consecutive smears have been negative. If specific infections are identified, the patient should be reevaluated after appropriate treatment for those infections. In all follow-up strategies using repeated Pap smears, the tests not only must be negative but also must be interpreted by the laboratory as "satisfactory for evaluation."

Because many public health clinics, including most STD clinics, cannot provide clinical follow-up of abnormal Pap smears with colposcopy and biopsy, women with Pap smears demonstrating high grade SIL or persistent low-grade SIL or ASCUS usually will need a referral to other local health-care providers or clinics for colposcopy and biopsy. Clinics and health-care providers who offer Pap smear screening services but cannot provide appropriate colposcopic follow-up of abnormal Pap smears should arrange referral services that a) can promptly evaluate and treat patients and b) will report the results of the evaluation to the referring clinician or health-care provider. Clinics and health-care providers should develop protocols that identify women who miss initial appointments (i.e., so that these women can be scheduled for repeat Pap smears), and they should reevaluate such protocols routinely. Pap smear results, type and location of follow-up appointments, and results of follow-up should be clearly documented in the clinic record. The development of colposcopy and biopsy services in local health departments, especially in circumstances where referrals are difficult and follow-up is unlikely, should be considered.

Other Management Considerations

 

Other considerations in performing Pap smears are as follows:

·         The Pap smear is not an effective screening test for STDs.

·         If a woman is menstruating, a Pap smear should be postponed, and the woman should be advised to have a Pap smear at the earliest opportunity.

·         The presence of a mucopurulent discharge might compromise interpretation of the Pap smear. However, if the woman is unlikely to return for follow-up, a Pap smear can be obtained after careful removal of the discharge with a saline-soaked cotton swab.

·         A woman who has external genital warts does not need to have Pap smears more frequently than a woman who does not have warts, unless otherwise indicated.

·         In an STD clinic setting or when other cultures or specimens are collected for STD diagnoses, the Pap smear may be obtained last.

·         Women who have had a hysterectomy do not require an annual Pap smear unless the hysterectomy was related to cervical cancer or its precursor lesions. In this situation, women should be advised to continue follow-up with the physician(s) who provided health care at the time of the hysterectomy.

·         Both health-care providers who receive basic retraining on Pap smear collection and clinics that use simple quality assurance measures obtain fewer unsatisfactory smears.

·         Although type-specific HPV testing to identify women at high and low risk for cervical cancer may become clinically relevant in the future, its utility in clinical practice is unclear, and such testing is not recommended.

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 in pregnant women, although care should be taken not to disrupt the mucous plug.

 

HIV Infection

 

Several studies have documented an increased prevalence of SIL in HIV-infected women, and HIV is believed by many experts to hasten the progression of precursor lesions to invasive cervical cancer. The following recommendations for Pap smear screening among HIV-infected women are consistent with other guidelines published by the U.S. Department of Health and Human Services (10,11,27,28) and are based partially on the opinions of experts in the care and management of cervical cancer and HIV infection in women.

After obtaining a complete history of previous cervical disease, HIV-infected women should have a comprehensive gynecologic examination, including a pelvic examination and Pap smear as part of their initial evaluation. A Pap smear should be obtained twice in the first year after diagnosis of HIV infection and, if the results are normal, annually thereafter. If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology (28). Women who have a cytological diagnosis of high-grade SIL or squamous cell carcinoma should undergo colposcopy and directed biopsy. HIV infection is not an indication for colposcopy in women who have normal Pap smears.

 

By Julia Tortorice, RN, MBA, CPHQ

 

Excerpts reprinted from the CDC publication, 1998 Guidelines for Treatment of Sexually Transmitted Diseases, January 23, 1998 / 47(RR-1);1-118, mmwrq@cdc.gov.

 

 

References

1.       CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination -- recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(No. RR-13).

2.       CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1996;45(No. RR-15).

3.       CDC. Sexually transmitted diseases clinical practice guidelines, 1991. Atlanta: US Department of Health and Human Services, Public Health Service, CDC, 1991.

4.       Hatcher RA, Trussell J, Stewart F, et al. Contraceptive technology. 16th ed. New York: Irvington Publishers, 1994.

5.       CDC. Technical guidance on HIV counseling. MMWR 1993;42(No. RR-2):11-7.

6.       American Academy of Pediatrics/American College of Obstetricians and Gynecologists. Guidelines for perinatal care. 3rd ed. Elk Grove Village, IL: American Academy of Pediatrics/American College of Obstetricians and Gynecologists, 1992.

7.       U.S. Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore: Williams and Wilkins, 1996.

8.       American College of Obstetricians and Gynecologists. Gonorrhea and chlamydial infections. Washington, DC: American College of Obstetricians and Gynecologists, March 1994. (ACOG technical bulletin, no. 190).

9.       CDC. Recommendations for the prevention and management of Chlamydia trachomatis infections, 1993. MMWR 1993;42(No. RR-12).

10.   CDC. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR 1997;46(No. RR-12).

11.   Agency for Health Care Policy and Research. Evaluation and management of early HIV infection. Rockville, MD: US Department of Health and Human Services, Public Health Service, 1994; AHCPR publication no. 94-0572. (Clinical practice guidelines, no. 7).

12.   CDC. Testing for antibodies to human immunodeficiency virus type 2 in the United States. MMWR 1992;41(No. RR-12).

13.   CDC. Purified protein derivative (PPD)-tuberculin anergy and HIV infection: guidelines for anergy testing and management of anergic persons at risk of tuberculosis. MMWR 1991;40(No. RR-5):27-33.

14.   CDC. The use of preventive therapy for tuberculous infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1990;39(No. RR-8):9-12.

15.   CDC. Management of persons exposed to multidrug-resistant tuberculosis. MMWR 1992;41(No. RR-11):59-71.

16.   Carpenter CCJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society -- USA Panel. JAMA 1997;277:1962-9.

17.   CDC. Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus: U.S. Public Health Service Task Force on Antipneumocystis Prophylaxis for Patients with Human Immunodeficiency Virus Infection. MMWR 1992;41(No. RR-4).

18.   CDC. 1995 Revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. MMWR 1995;44(No. RR-4).

19.   Committee on Infectious Diseases, American Academy of Pediatrics. Report of the Committee on Infectious Diseases. 22nd ed. Elk Grove Village, IL: American Academy of Pediatrics, 1991.

20.   CDC. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993;42(No. RR-4).

21.   CDC. U.S. Public Health Service recommendations for human immunodeficiency virus counseling and voluntary testing for pregnant women. MMWR 1995;44(No. RR-7).

22.   CDC. Recommendations of the U.S. Public Health Service Task Force on the Use of Zidovudine to Reduce Perinatal Transmission of Human Immunodeficiency Virus. MMWR 1994;43(No. RR-11).

23.   Henry RE, Wegmann JA, Hartle JE, Christopher GW. Successful oral acyclovir desensitization. Ann Allergy 1993;70:386-8.

24.   Wendel GD Jr, Stark BJ, Jamison RB, Molina RD, Sullivan TJ. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med 1985;312:1229-32.

25.   Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics {Clinical conference}. Ann Intern Med 1987;107:204-15.

26.   Pearlman MD, Yashar C, Ernst S, Solomon W. An incremental dosing protocol for women with severe vaginal trichomoniasis and adverse reactions to metronidazole. Am J Obstet Gynecol 1996;174:934-6.

27.   National Cancer Institute Workshop. The 1988 Bethesda System for reporting cervical/vaginal cytological diagnoses. JAMA 1989;262:931-4.

28.   Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH, National Cancer Institute Workshop. Interim guidelines for management of abnormal cervical cytology. JAMA 1994;271:1866-9.

29.   Committee on Child Abuse and Neglect, American Academy of Pediatrics. Guidelines for the evaluation of sexual abuse of children. Pediatrics 1991;87:254-60.


Expert Consultants

Chairman: David Atkins, M.D., M.P.H., Agency for Health Care Policy and Research;

Presenters: Michael H. Augenbraun, M.D., State University of New York Health Science Center at Brooklyn, NY; Karl Beutner, M.D., Ph.D., Solano Dermatology, Vallejo, CA; Gail A. Bolan, M.D., San Francisco Department of Public Health and University of California at San Francisco; Willard Cates, Jr., M.D., M.P.H., Family Health International, Research Triangle Park, NC; Anne M. Rompalo, M.D., Johns Hopkins University, Baltimore; Pablo J. Sanchez, M.D., Southwestern Medical Center at Dallas; Bradley Stoner, M.D., Ph.D., Washington University School of Medicine, St. Louis, MO; Anna Wald, M.D., M.P.H., University of Washington, Seattle; Cheryl K. Walker, M.D., University of California at Irvine; George D. Wendel, M.D., Southwestern Medical Center at Dallas; Jonathan M. Zenilman, M.D., Johns Hopkins University, Baltimore.

Moderators: King K. Holmes, M.D., Ph.D., Center for AIDS and STDs, University of Washington, Seattle; Edward W. Hook, III, M.D., University of Alabama at Birmingham School of Medicine; A. Eugene Washington, M.D., M.Sc., University of California at San Francisco.

Rapporteurs: John M. Douglas, Jr., M.D., Denver Department of Public Health and University of Colorado Health Science Center; Margaret R. Hammerschlag, M.D., State University of New York Health Science Center; David H. Martin, M.D., Louisiana State University Medical Center, New Orleans.

Consultants: Adaora A. Adimora, M.D., M.P.H., University of North Carolina at Chapel Hill; Virginia A. Caine, M.D., Marion County Health Department, Indianapolis; Laura T. Gutman, M.D., Duke University, Durham, NC; H. Hunter Handsfield, M.D., Seattle-King County Department of Public Health and University of Washington, Seattle; Robert B. Jones, M.D., Ph.D., Indiana University, Indianapolis; Franklyn N. Judson, M.D., Denver Department of Health; William M. McCormack, M.D., State University of New York Health Science Center at Brooklyn; Daniel M. Musher, M.D., Baylor College of Medicine, Houston; Newton G. Osborne, M.D., M.P.H., Howard University Hospital, Washington, DC; Robert T. Rolfs, Jr., M.D., Utah Department of Health; Lawrence L. Sanders, Jr., M.D., Southwest Hospital and Medical Center, Atlanta; Jane R. Schwebke, M.D., University of Alabama at Birmingham School of Medicine; Jack D. Sobel, M.D., Wayne State University School of Medicine, Detroit; David E. Soper, M.D., Medical University of South Carolina, Charleston; Walter E. Stamm, M.D., University of Washington; Lawrence R. Stanberry, M.D., Ph.D., Children's Hospital, Cincinnati; Felicia H. Stewart, M.D., Kaiser Family Foundation, Menlo Park, CA; Richard L. Sweet, M.D., Magee-Women's Hospital, Pittsburgh.

Other Expert Consultants (did not attend meeting): Susan Blank, M.D., New York City Department of Health; Sharon L. Hillier, Ph.D., University of Pittsburgh; Penelope J. Hitchcock, D.V.M., M.S., National Institutes of Health; Paul N. Zenker, M.D., M.P.H., Franklin Primary Health, Mobile, AL.

Liaison Participants: Dennis J. Barbour, J.D., Association of Reproductive Health Professionals; Joan R. Cates, American Social Health Association; JoAnne Doherty, Health Canada, Ontario; Robert G. Harmon, M.D., M.P.H., United Health Care; Kate L. Heilpern, M.D., American College of Emergency Physicians; John J. Henning, Ph.D., American Medical Association; K. King Holmes, M.D., Ph.D., Infectious Diseases Society of America; John N. Krieger, M.D., American Urological Association; Marshall Kubota, M.D., American Academy of Family Practice; Noni E. MacDonald, M.D., American Academy of Pediatrics; Gary A. Richwald, M.D., M.P.H., National Coalition of STD Directors; Helen J. Sawyer, R.N., Georgia Department of Human Resources; Stanley X. Shapiro, M.D., Regional Laboratory and Infectious Disease Committee, Kaiser Permanente, Panorama City, CA; Donald Sutherland, M.D., Health Canada; Steve K. Tyring, M.D., Ph.D., American Academy of Dermatology; C. Johannes van Dam, M.D., World Health Organization; Fernando Zacarias, M.D., M.P.H., Pan American Health Organization, World Health Organization.

CDC/Division of STD Prevention (DSTDP)/STD Treatment Guidelines 1997 Project

Coordinators: Kimberly A. Workowski, M.D.; John S. Moran, M.D.; Co-Chair: Michael E. St. Louis, M.D.; Co-Moderator: Katherine M. Stone, M.D.;

Presenters: Consuelo M. Beck-Sague, M.D., National Center for Infectious Diseases (NCID); M. Riduan Joesoef, M.D., Ph.D., M.P.H.; Mary L. Kamb, M.D., M.P.H., Division of HIV/AIDS Prevention (DHAP); Jonathan E. Kaplan, M.D., NCID; H. Trent MacKay, M.D., M.P.H.; Michael M. McNeil, M.D., M.P.H., NCID; Allyn K. Nakashima, M.D., DHAP; George P. Schmid, M.D., M.Sc.;

Consultants: Sevgi O. Aral, Ph.D.; Stuart M. Berman, M.D.; Donald F. Dowda; Brian R. Edlin, M.D., DHAP; Helene D. Gayle, M.D., M.P.H., National Center for HIV, STD, and TB Prevention (NCHSTP); Robert S. Janssen, M.D., DHAP; Wanda K. Jones, Dr.P.H., Office of Women's Health; William J. Kassler, M.D., M.P.H.; Nancy C. Lee, M.D., DHAP; Beth Macke, Ph.D.; Frank J. Mahoney, M.D., NCID; Phillip I. Nieberg, M.D., M.P.H., NCHSTP; Herbert B. Peterson, M.D., National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP); Martha F. Rogers, M.D., DHAP; William E. Secor, Ph.D., NCID; Dawn K. Smith, M.D., DHAP; Ronald O. Valdiserri, M.D., M.P.H., NCHSTP; Judith N. Wasserheit, M.D., M.P.H.; Lynne S. Wilcox, M.D., NCCDPHP;

Support Staff: Cynthia Ford, Contractor; Deborah McElroy; Garrett K. Mallory.