Sexually Transmitted Diseases Treatment Guidelines

Epididymitis

Among sexually active men aged <35 years, epididymitis is most often caused by C. trachomatis or N. gonorrhoeae. Epididymitis caused by sexually transmitted enteric organisms (e.g., Escherichia coli) also occurs among men who are the insertive partner during anal intercourse. Sexually transmitted epididymitis usually is accompanied by urethritis, which often is asymptomatic. Nonsexually transmitted epididymitis that is associated with urinary-tract infections caused by Gram-negative enteric organisms occurs more frequently among men aged >35 years, men who have recently undergone urinary-tract instrumentation or surgery, and men who have anatomical abnormalities of the urinary tract.

Although most patients can be treated on an outpatient basis, hospitalization should be considered when severe pain suggests other diagnoses (e.g., torsion, testicular infarction, or abscess) or when patients are febrile or might be noncompliant with an antimicrobial regimen.

Diagnostic Considerations

Men who have epididymitis typically have unilateral testicular pain and tenderness; hydrocele and palpable swelling of the epididymis usually are present. Testicular torsion, a surgical emergency, should be considered in all cases, but it occurs more frequently among adolescents and in men without evidence of inflammation or infection. Emergency testing for torsion may be indicated when the onset of pain is sudden, pain is severe, or the test results available during the initial examination do not support a diagnosis of urethritis or urinary-tract infection. If the diagnosis is questionable, a specialist should be consulted immediately, because testicular viability may be compromised. The evaluation of men for epididymitis should include the following procedures.

A Gram-stained smear of urethral exudate or intraurethral swab specimen for diagnosis of urethritis (i.e., >5 polymorphonuclear leukocytes per oil immersion field) and for presumptive diagnosis of gonococcal infection.
A culture of intraurethral exudate or a nucleic acid amplification test (either on intraurethral swab or first-void urine) for N. gonorrhoeae and C. trachomatis.
Examination of first-void uncentrifuged urine for leukocytes if the urethral Gram stain is negative. A culture and Gram-stained smear of this urine specimen should be obtained.
Syphilis serology and HIV counseling and testing.

Treatment

Empiric therapy is indicated before culture results are available. Treatment of epididymitis caused by C. trachomatis or N. gonorrhoeae will result in a) microbiologic cure of infection, b) improvement of signs and symptoms, c) prevention of transmission to others, and d) a decrease in potential complications (e.g., infertility or chronic pain). As an adjunct to therapy, bed rest, scrotal elevation, and analgesics are recommended until fever and local inflammation have subsided.

Recommended Regimens

For epididymitis most likely caused by gonococcal or chlamydial infection:

Ceftriaxone 250 mg IM in a single dose
PLUS
Doxycycline 100 mg orally twice a day for 10 days.

For epididymitis most likely caused by enteric organisms, for patients allergic to cephalosporins and/or tetracyclines, or for epididymitis in patients aged >35 years:

Ofloxacin 300 mg orally twice a day for 10 days^§§
OR
Levofloxacin 500 mg orally once daily for 10 days.^§§

Follow-Up

Failure to improve within 3 days of the initiation of treatment requires reevaluation of both the diagnosis and therapy. Swelling and tenderness that persist after completion of antimicrobial therapy should be evaluated comprehensively. The differential diagnosis includes tumor, abscess, infarction, testicular cancer, TB, and fungal epididymitis.

Management of Sex Partners

Patients who have epididymitis that has been confirmed or is suspected to be caused by N. gonorrhoeae or C. trachomatis should be instructed to refer sex partners for evaluation and treatment. Sex partners of these patients should be referred if their contact with the index patient was within the 60 days preceding onset of the patient's symptoms.

Patients should be instructed to avoid sexual intercourse until they and their sex partners are cured (i.e., until therapy is completed and patient and partner[s] no longer have symptoms).

Special Considerations

HIV Infection

Patients who have uncomplicated epididymitis and also are infected with HIV should receive the same treatment regimen as those who are HIV-negative. Fungi and mycobacteria, however, are more likely to cause epididymitis in immunosuppressed patients than in those who are immunocompetent.

Human Papillomavirus Infection

Genital Warts

More than 30 types of HPV can infect the genital tract. Most HPV infections are asymptomatic, unrecognized, or subclinical. Visible genital warts usually are caused by HPV types 6 or 11. Other HPV types in the anogenital region (e.g., types 16, 18, 31, 33, and 35) have been strongly associated with cervical neoplasia. Diagnosis of genital warts can be confirmed by biopsy, although biopsy is needed only under certain circumstances (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.

In addition to the external genitalia (i.e., the penis, vulva, scrotum, perineum, and perianal skin), genital warts can occur on the uterine cervix and in the vagina, urethra, anus, and mouth; these warts are sometimes symptomatic. Intra-anal warts are seen predominantly 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. In addition to the genital area, HPV types 6 and 11 have been associated with conjunctival, nasal, oral, and laryngeal warts. HPV types 6 and 11 rarely are associated with invasive squamous cell carcinoma of the external genitalia. Depending on the size and anatomic location, genital warts can be painful, friable, and pruritic, although they are commonly asymptomatic.

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 also 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. In most patients, treatment can induce wart-free periods. If left untreated, visible genital warts may resolve on their own, remain unchanged, or increase in size or number. Determining whether treatment of genital warts will reduce transmission is difficult, because no laboratory marker of infectivity has been established and because clinical studies evaluating the persistence of HPV DNA in genital tissue after treatment have shown variable results. Existing data indicate that currently available therapies for genital warts may reduce, but probably do not eradicate, infectivity. Whether the reduction in viral DNA that results from current treatment regimens impacts future transmission remains unclear. No evidence indicates that either the presence of genital warts or their treatment is associated with 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. No definitive evidence suggests that any of the available treatments is superior to the others, and no single treatment is ideal for all patients or all warts. The use of locally developed and monitored treatment algorithms has been associated with improved clinical outcomes and should be encouraged. Because of uncertainty regarding the effect of treatment on future transmission and the possibility for spontaneous resolution, an acceptable alternative for some patients is to forego treatment and await spontaneous resolution.

Most patients have <10 genital warts, with a total wart area of 0.5--1.0 cm². These warts respond to most treatment modalities. Factors that may 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. Many patients 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 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. Both patient-applied therapies and provider-administered therapies are available. 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 persistent hypopigmentation or hyperpigmentation are common with ablative modalities. Depressed or hypertrophic scars are uncommon but can occur, especially if the patient has had insufficient time to heal between treatments. Rarely, treatment can result in disabling chronic pain syndromes (e.g., vulvodynia or hyperesthesia of the treatment site).

Recommended Regimens for External Genital Warts

Patient-Applied:

Podofilox 0.5% solution or gel. Patients should 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 up to four cycles. The total wart area treated should not exceed 10 cm², and the total volume of podofilox should be limited to 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 once daily at bedtime, three times a week for up to 16 weeks. The treatment area should be washed with soap and water 6--10 hours after the application. The safety of imiquimod during pregnancy has not been established.

Provider-Administered:

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

Alternative Regimens

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, an antimitotic drug that destroys warts, is relatively inexpensive, easy to use, safe, and self-applied by patients. 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. Local inflammatory reactions are common with the use of imiquimod; these reactions usually are mild to moderate. Traditionally, follow-up visits are not required for patients using self-administered therapy. However, follow-up may be useful several weeks into therapy to determine appropriateness of medication use and response to treatment.

Cryotherapy destroys warts by thermal-induced cytolysis. Health-care providers must be trained on the proper use of this therapy, because over- and under-treatment may result in poor efficacy or increased likelihood of complications. Pain after application of the liquid nitrogen, followed by necrosis and sometimes blistering, is common. Local anesthesia (topical or injected) may facilitate therapy if warts are present in many areas or if the area of warts is large.

Podophyllin resin, which contains several compounds including antimitotic podophyllin lignans, is another treatment option. The resin is most frequently compounded at 10%--25% in a 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. A thin layer of podophyllin resin must be applied to the warts and allowed to air dry before the treated area comes into contact with clothing; over-application 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 with that of water and can spread rapidly if applied excessively; thus, they can damage adjacent tissues. 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.

Surgical therapy is a treatment option that has the advantage of usually eliminating warts at a single visit. However, such therapy requires substantial clinical training, additional equipment, and a longer office visit. Once local anesthesia is applied, the visible genital warts can be physically destroyed by electrocautery, in which case no additional hemostasis is required. Care must be taken to control the depth of electrocautery to prevent scarring. 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. Surgical therapy 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 likely effective because of its anti-viral 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 all 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). However, some specialists believe that combining modalities may increase complications without improving efficacy.

Cervical Warts

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

Recommended Regimens for 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 to warts. A small amount should be applied only to warts and allowed to dry, at which time a white "frosting" develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate (i.e., baking soda), or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.

Recommended Regimens for 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. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established.

NOTE: Although data evaluating the use of podofilox and imiquimod for the treatment of distal meatal warts are limited, some specialists recommend their use in certain patients.

Recommended Regimens for Anal Warts

Cryotherapy with liquid nitrogen
OR
TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white "frosting" develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate (i.e., baking soda), or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
OR
Surgical removal.

NOTE: Warts on the rectal mucosa should be managed in consultation with a specialist.

Recommended Regimens for Oral Warts

Cryotherapy with liquid nitrogen
OR
Surgical removal.

Education and counseling are important aspects of managing patients with genital warts. Patients can be educated through patient education materials, including pamphlets, hotlines, and web sites (http://www.ashastd.org). Attempts should be made to cover the following key messages.

Genital HPV infection is a viral infection that is common among sexually active adults.
Infection is almost always sexually transmitted, but the incubation period is variable and it is often difficult to determine the source of infection. Within ongoing relationships, sex partners usually are infected by the time of the patient's diagnosis, although they may have no symptoms or signs of infection.
The natural history of genital warts is generally benign; the types of HPV that usually cause external genital warts are not associated with cancer. Recurrence of genital warts within the first several months after treatment is common and usually indicates recurrence rather than reinfection.
The likelihood of transmission to future partners and the duration of infectivity after treatment are unknown. The use of latex condoms has been associated with a lower rate of cervical cancer, an HPV-associated disease.
Because genital HPV is common among persons who have been sexually active and because the duration of infectivity is unknown, the value of disclosing a past diagnosis of genital HPV infection to future partners is unclear. Candid discussions about other STDs should be encouraged and attempted whenever possible.

Follow-Up

After visible genital warts have cleared, a follow-up evaluation is not mandatory but may be helpful. 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 are unknown, patients concerned about recurrences should be offered a follow-up evaluation 3 months after treatment. Earlier follow-up visits also may be useful for some patients to document the absence of warts, to monitor for or treat complications of therapy, and to provide an additional opportunity for patient education and counseling. Women should be counseled to undergo regular Pap screening as recommended for women without genital warts. The presence of genital warts is not an indication for a change in the frequency of Pap tests or for cervical colposcopy.

Management of Sex Partners

Examination of sex partners is not necessary for the management of genital warts because no data indicate that reinfection plays a role in recurrences. Additionally, providing treatment solely for the purpose of preventing future transmission cannot be recommended because the value of treatment in reducing infectivity is not known. 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. The counseling of sex partners provides an opportunity for these partners to a) learn about implications of having a partner who has genital warts and about their potential for future disease transmission and b) receive STD and Pap screening. 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

Pregnancy

Imiquimod, podophyllin, and podofilox should not be used during pregnancy. Because genital warts can proliferate and become friable during pregnancy, many specialists advocate their removal during pregnancy. HPV types 6 and 11 can cause respiratory 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. 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.

Immunodeficient 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 may occur more frequently among immunosuppressed persons, thus requiring biopsy for confirmation of diagnosis. Because of the increased incidence of anal cancer in HIV-infected homosexual men, screening for anal SIL by cytology in this population is advocated by some specialists. However, until more data about the natural history of anal SIL and treatment efficacy are available, such a screening approach is not recommended.

Squamous Cell Carcinoma in Situ

Patients in whom squamous cell carcinoma in situ of the genitalia is diagnosed should be referred to a specialist 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 male 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 is a term often used to refer to manifestations of infection in the absence of genital warts, including situations where infection is detected on the cervix by Pap test, colposcopy, or biopsy; on the penis, vulva, or other genital skin by the appearance of white areas after application of acetic acid; or on any genital skin by a positive test for HPV.

Subclinical genital HPV infection occurs more frequently than visible genital warts among both men and women. Subclinical infection of the cervix is most commonly diagnosed by Pap screening with the detection of squamous intraepithelial lesions. The application of 3%--5% acetic acid usually turns HPV-infected genital mucosal tissue a whitish color. However, acetic acid application is not a specific test for HPV infection, and the specificity and sensitivity of this procedure for screening have not been defined. Thus, the routine use of this procedure for screening to detect subclinical infection is not recommended. However, some experienced clinicians find this test useful for identification of flat genital warts.

A definitive diagnosis of HPV infection is based on detection of viral nucleic acid (DNA or RNA) or capsid protein. Pap-test 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 SIL and often regress spontaneously without treatment. Tests that detect several types of HPV DNA in cells scraped from the cervix are available and may be useful in the triage of women with atypical squamous cells of undetermined significance (ASCUS) but not other types of cytologic abnormalities. Screening for subclinical genital HPV infection using DNA or RNA tests is not recommended.

Treatment

In the absence of coexistent SIL, treatment is not recommended for subclinical genital HPV infection diagnosed by colposcopy, biopsy, acetic acid application, or the detection of HPV by laboratory tests. The diagnosis of subclinical genital HPV infection is often not definitive, and no therapy has been identified that eradicates infection. In the presence of coexistent SIL, management should be based on histopathologic findings.

Management of Sex Partners

Examination of sex partners is unnecessary. Most sex partners of infected patients probably are already infected subclinically with HPV. No screening tests for subclinical infection are available. Likewise, whether patients who have subclinical HPV infection are as infectious as patients who have exophytic warts is unknown.

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

Women with a history of STD may be 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 (92). The cervical Pap test is an effective, low-cost screening test for preventing invasive cervical cancer. Recommendations regarding Pap testing intervals vary in the United States (93,94,10). However, if a woman has three consecutive negative annual Pap tests, future screening tests may be performed less frequently.

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 test and discuss the following information with the patient:

the purpose and importance of a Pap test;
whether a Pap test was obtained during the clinic visit;
the need for a regular Pap test; and
if a Pap test was not obtained during this examination, the names of local providers or referral clinics that can obtain Pap tests and adequately follow up results.

If a woman has not had a Pap test during the previous 12 months, a Pap test may be obtained as part of the routine pelvic examination. Health-care providers should be aware that many women believe they have had a Pap test when they actually have received only a pelvic examination, and thus may report having had a recent Pap test. Therefore, in STD clinics, a Pap test should be strongly considered during the routine clinical evaluation of women who do not have clinical-record documentation of having had a normal Pap test within the preceding 12--36 months.

A woman may benefit from receiving printed information about Pap tests and a report containing a statement that a Pap test was obtained during her clinic visit. If possible, a copy of the Pap test result should be provided to the patient for her records.

Follow-Up

Clinicians who offer Pap test screening services are encouraged to use cytopathology laboratories that report results using the Bethesda System of classification^†††. If the results of the Pap test 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 (95). Appropriate follow-up of Pap tests showing high-grade SIL always includes referral to a clinician who can provide a colposcopic examination of the lower genital tract and, if indicated, colposcopically directed biopsy. For patients who have a Pap test indicative of low-grade SIL or ASCUS, follow-up without colposcopy may be acceptable in some circumstances. Such follow-up would involve repeat Pap tests every 4--6 months for 2 years until the results of three consecutive tests are negative. If repeat tests show persistent abnormalities, colposcopy and directed biopsy may be indicated. However, if compliance with follow-up is in question, women with low-grade SIL or ASCUS may be considered for colposcopy. If specific infections other than HPV are identified, the patient should be reevaluated after appropriate treatment for those infections. In all follow-up strategies using repeat Pap tests, the tests not only must be negative but also must be interpreted by the laboratory as "satisfactory for evaluation." Tests determined by the laboratory to be "satisfactory but limited by…" in conjunction with a diagnosis of "negative" or "within normal limits" are also considered negative.

Another strategy for management of patients with ASCUS Pap tests involves testing for HPV DNA. If high-risk types of HPV DNA are detected, women with ASCUS tests are referred immediately for colposcopy. Because many public health clinics, including most STD clinics, cannot provide clinical follow-up of abnormal Pap tests, women with Pap tests demonstrating high grade SIL, persistent low-grade SIL, or ASCUS usually need a referral to other local health-care providers or clinics for colposcopy and biopsy. Clinics and health-care providers who offer Pap test screening services but cannot provide appropriate colposcopic follow-up of abnormal Pap tests should arrange referral to services in which a) a patient will be promptly evaluated and treated and b) the results of the evaluation will be reported to the referring clinic or health-care provider. Clinics and health-care providers should develop protocols that identify women who miss follow-up appointments so that these women can be scheduled for repeat Pap tests, and they should reevaluate such protocols routinely. Pap test results, type and location of follow-up appointments, and results of follow-up should be clearly documented in the clinic record. The establishment of colposcopy and biopsy services in local health departments, especially in circumstances where referrals are difficult and follow-up is unlikely, should be considered.

^††† The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses uses the terms "low-grade SIL" and "high-grade SIL" (95). Low-grade SIL encompasses cellular changes associated with HPV and mild dysplasia/cervical intraepithelial neoplasia 1 (CIN1). High-grade SIL includes moderate dysplasia/CIN2, severe dysplasia/CIN3, and carcinoma in situ/CIN3.

Other Management Considerations

Other considerations in performing Pap tests are as follows.

The Pap test is not a screening test for STDs.
If a woman is menstruating, a Pap test should be postponed, and the woman should be advised to have a Pap test at the earliest opportunity.
The presence of a mucopurulent discharge should not delay the Pap test. The test can be performed after careful removal of the discharge with a saline-soaked cotton swab.
Women who have external genital warts do not need to have Pap tests more frequently than women who do not have warts, unless otherwise indicated.
The sequence of Pap testing in relation to other cervicovaginal specimens does not appear to influence Pap test results or their interpretation. Therefore, when other cultures or specimens are collected for STD diagnoses, the Pap test can be obtained last.
Women who have had a hysterectomy do not require a routine Pap test unless the hysterectomy was performed as a result of 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.
Health-care providers who receive basic retraining on Pap-test collection and clinics that use simple quality assurance measures obtain fewer unsatisfactory tests. The use of cytobrushes also improves the number of satisfactory Pap tests.
Emerging data support the option of HPV testing for the triage of women who have ASCUS Pap tests. However, experience is limited and studies to define its value and cost-effectiveness are ongoing. The HPV testing strategy may be most cost-effective when conducted as "reflex testing," in which samples collected at the initial visit can be tested for HPV after the Pap test results are available. This approach requires the collection of a cervical swab placed in liquid media (i.e., liquid-based cytology or collection of a separate swab stored in HPV transport media).
Liquid-based cytology is an alternative to conventional Pap tests. It has a higher sensitivity for detection of SIL and can facilitate HPV testing in women with ASCUS. However, it may also have a lower specificity, resulting in more false-positive tests and more administrative and patient-related costs, which could reduce the cost-effectiveness of cervical cancer screening.

Special Considerations

Pregnancy

Pregnant women should have a Pap test as part of routine prenatal care. A cytobrush may be used for obtaining Pap tests 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 (96). The following recommendations for Pap test screening among HIV-infected women are consistent with other guidelines published by the U.S. Department of Health and Human Services (21) and are based partially on the opinions of professionals knowledgeable 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 be provided a comprehensive gynecologic examination, including a pelvic examination and Pap test, as part of their initial evaluation. A Pap test 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 test are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology (97). 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 tests.