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Warning:
This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:
- STD Treatment Guidelines at http://www.cdc.gov/STD/treatment
1998 Guidelines for Treatment of Sexually Transmitted Disease
Date: 01/23/98
Source: 47(RR-1);1-118
SUGGESTED CITATION: Centers for Disease Control and Prevention. 1998 Guidelines for Treatment of Sexually Transmitted Diseases. MMWR 1998;47(No. RR-1): {inclusive page numbers}.
The material in this report was prepared for publication by: National Center for HIV, STD and TB Prevention, Division of Sexually Transmitted Diseases Prevention
HUMAN PAPILLOMAVIRUS INFECTION
Genital Warts
More than 20 types of 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, bowen-oid 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, ana-tomic 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.
External 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.
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p>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
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.
