Chapter 44. Sexually Transmitted Infections in Adolescents

According to the Centers for Disease Control and Prevention's (CDC) 2005 Youth Risk Behavior Surveillance survey, nearly one-half of US high school students report ever having had sexual intercourse.1 Over 60% of high school seniors report a history of sexual intercourse, while 20% of seniors report having had at least four sexual partners. Even higher numbers of adolescents engage in other, noncoital sexual behaviors, including oral sex.2–4 Young people age 15–24 years old make up one-fourth of sexually active individuals in the United States, yet acquire nearly one-half of all new sexually transmitted infections (STIs) each year.5 Sexually active adolescents are at high risk for contracting STIs for a variety of reasons. While many adolescents report the use of condoms, they are not necessarily using them consistently or correctly.6,7 They are more likely than adults to experiment with multiple sexual partners,8–10 to engage in riskier sex while under the influence of alcohol or drugs,8,11 to have a poor understanding of STI transmission and consequences of infection,12 and to face barriers to accessing confidential health care.13,14 In addition, the presence of columnar epithelial cells in the cervical ectropion of female adolescents increases susceptibility to infection with certain sexually transmitted organisms.

This chapter will focus on four sexually transmitted genital infections commonly found in the adolescent population. Three of these infections—chlamydia, trichomoniasis, and human papillomavirus (HPV)—together account for nearly 90% of new STIs among 15–24-years-old youth.15 Gonorrhea, the second most common infection reported to the CDC and a significant risk factor for chronic reproductive health problems, will be discussed in the section with chlamydia as a major cause of cervicitis and urethritis in teenagers.

Epidemiology

Chlamydia is the most frequently reported STI in the United States, with an estimated 3 million cases annually. At least 70% of genital chlamydia infections are in adolescents and young adults, 15–24 years old.5 CDC surveillance data has repeatedly shown infection rates to be highest in 15–19-years-old females. In 2005, the rate of chlamydia infection in adolescent females (15–19 years old) was nearly 2,800 per 100,000 population.16 Rates in males are highest for 20- to 24-year olds, with 805 per 100,000 population, followed next by males 15- to 19-year olds (505 per 100,000 population). This reflects common patterns of partnering, in which adolescent women are more commonly engaging in sex with slightly older males.

Gonorrhea, the second most common reportable disease, has infection rates similar in distribution to those of chlamydia infections. In 2005, adolescents aged 15–19 years had the highest reported rates of gonorrhea among women, with reported rates of 625 per 100,000 population.16 Rates in males are highest for 20- to 24-year olds, with 437 per 100,000 population, followed next by 15- to 19-year-old males, with 261 per 100,000 population.

Pathogenesis

Chlamydia trachomatis is an obligate intracellular bacterium that infects mucosal columnar epithelial cells, particularly of the cervix and urethra. The organism, transmitted through secretions, attaches to these epithelial cells, enters them, and begins to replicate. The replication process induces an immune response and cell wall rupture. The bursting of the epithelial cell contributes to cell death and the release of more infectious particles, which infect nearby cells and are transmitted to other hosts through sexual contact.17 Symptoms may develop after a 1–3-week incubation period, but mucosal damage may go undetected by infected individuals.

Neisseria gonorrhoeae is a gram-negative intracellular diplococcus. Several of its outer membrane proteins facilitate attachment to mucosal epithelial cells found in the genitourinary tract and other mucous membranes. Host defenses can be evaded through adaptation and alteration of these surface structures. Cytotoxicity and inflammation contribute to mucosal damage and its accompanying symptomatology.18 As with chlamydia, patients with genital infections caused by N. gonorrhoeae may be asymptomatic for months.

The asymptomatic nature of these infections in many patients poses increased risk for transmission, especially when considering adolescent cognitive development. Teenagers who have not progressed from concrete to abstract thinking are likely to equate the absence of symptoms with the absence of infection. Combining this thinking with an adolescent's perceived sense of invincibility makes him or her less likely to take precautions (e.g., condom use) when engaging in sexual activity.

Female adolescents are particularly at risk for chlamydia and gonorrhea infections because of the presence of cervical ectopy, or the ectropion.19 As girls progress through puberty, columnar epithelium on the ectocervix undergoes transformation to squamous epithelial cells. The persistence of columnar cells on the ectocervix of adolescent females forms a ring around the os known as the ectropion. Its presence increases the risk for acquiring a cervicitis, as columnar cells are particularly susceptible to invasion by N. gonorrhoeae and C. trachomatis.20

Clinical Presentation

Cervicitis

The majority of adolescent females with cervicitis are asymptomatic.17 When symptoms are present, they can include a purulent vaginal discharge, vaginal spotting, dyspareunia, and irregular vaginal bleeding (see Table 44–1). A speculum examination in these patients may reveal an erythematous, edematous cervix with a mucopurulent discharge at the cervical os. Touching the cervix with a cotton-tipped swab can induce bleeding. This phenomenon, known as friability, is likely the underlying etiology of the bleeding these patients may experience after sexual intercourse. Saline microscopy of a vaginal swab may demonstrate a preponderance of white blood cells, usually >10 wbc/hpf.

Untreated cervicitis can lead to more complicated infections. N. gonorrhoeae or C. trachomatis, accompanied by a variety of vaginal microorganisms, can ascend into the upper reproductive tract, leading to pelvic inflammatory disease (PID) in 10–40% of untreated women.21 PID and its associated complications (tubo-ovarian abscess and perihepatitis, or Fitz–Hugh–Curtis syndrome) can lead to serious sequelae, such as infertility, ectopic pregnancy, and chronic pelvic pain.22,23 PID is discussed in depth in Chapter 43. N. gonorrhoeae can also infect Bartholin's and Skene's glands in the vulvar region, leading to painful abscesses, as well as spread hematogenously to cause a disseminated gonococcal infection (see Table 44–2).

Urethritis

The urethritis seen in men with chlamydia or gonorrhea is usually asymptomatic. Clinical manifestations are absent in over 90% of chlamydia infections and over 60% of gonorrhea urethral infections in males.24 When present, dysuria and urethral discharge are the more common symptoms experienced. The physical examination is usually unremarkable, although a clear to purulent discharge may be expressed from the urethral meatus. If the urethral infection spreads in a retrograde manner, infection of the epididymis can ensue. Patients with epididymitis present with scrotal pain and swelling, with clinical examination findings consistent with an enlarged, tender epididymis palpable in the scrotum. Urethritis may also accompany cervical infection in females. If the possibility of sexual activity is not considered in an adolescent female with dysuria and urinary frequency, health care providers may jump to presumptively treat such patients for a simple cystitis, thereby missing the opportunity to diagnose and treat an STI.

Although this discussion of chlamydia and gonorrhea is limited to cervical and urethral infections, other nongenital clinical syndromes resulting from sexual transmission of these organisms are listed in Table 44–2. These presentations may result as complications of genital infection, or as the result of noncoital behaviors, such as oral and anal sex.

Differential Diagnosis

The differential diagnosis of chlamydia and gonorrhea lower genital infection ranges from other STIs to noninfectious etiologies. Table 44–3 lists the common causes of vaginal discharge in adolescent females and urethritis in males. In addition to C. trachomatis and Trichomonas vaginalis (discussed below), Mycoplasma hominis, and Ureaplasma urealyticum have been implicated as less common causes of nongonococcal urethritis in males.

Diagnosis

Diagnostic tests include both culture and nonculture tests, such as nucleic acid amplification tests (NAATs), DNA hybridization (nonamplified DNA probe), and direct fluorescent antibody. Table 44–4 lists the relative sensitivities and specificities for each test. Culture tests, which are performed on cervical and urethral swab specimens, offer the advantage of high specificity (>99%). This makes it the preferred method for criminal investigations, such as cases of rape or sexual abuse. Culture for N. gonorrhoeae can also be used to determine antimicrobial susceptibility, which is increasingly important as antibiotic resistance continues to rise with this organism. The disadvantages of culture include relatively low sensitivity, problems maintaining organism viability in transport, and a longer turnaround time for results compared to nonculture tests.25 In addition, cultures are more invasive than some nonculture tests, given that females require a speculum examination to swab the cervix, while males require urethral swabs.

NAATs are an important addition to STI testing in adolescents. NAATs detect and amplify organism-specific DNA or RNA from both N. gonorrhoeae and C. trachomatis. Technologies used include polymerase chain reaction (PCR), strand displacement amplification, and transcription-mediated amplification. NAATs are advantageous because of their high sensitivity and specificity. In general, sensitivities are superior to culture, reaching as high as 98–99%.25,26 This is largely because of the fact that these tests can produce a signal from a single copy of target DNA or RNA, which also obviates the need to adequately collect and transport a viable organism (as is the case with culture). NAATs are advantageous in adolescents because of the potential for less invasive collection methods. Not only can they be performed on cervical and urethral swabs, but they can also be performed on first-void urine specimens, with no significant difference in sensitivity.25,26 This decreases the need to rely on speculum examinations and urethral swabs, which may be difficult or undesirable in certain patients or clinical settings. It also allows for routine asymptomatic screening programs targeting larger numbers of adolescents, a practice that is recommended by the CDC and the U.S. Preventive Services Task Force.27–29 Although they have the advantage of urine-based testing, NAATs cannot be used for pharyngeal or rectal specimens, an important consideration for adolescents engaging in oral and anal sex. These sites still require the use of culture.

Other nonculture tests include direct fluorescent antibody, nucleic acid hybridization (DNA probe), enzyme immunoassay for chlamydia, and Gram stain for gonorrhea. These tests, while cheaper, are used less frequently because of a lower sensitivity than NAATs and an inability to use them with urine specimens.25 Like NAATs, they cannot be used on other nongenital specimens (e.g., pharynx and rectum). Detection of intracellular gram-negative diplococci in polymorphonuclear leukocytes by Gram stain has a sensitivity of 90–95% for the diagnosis of gonorrhea in men; in women, endocervical samples may be colonized with other gram-negative coccobacillary organisms, thus resulting in a lower sensitivity (range, 50–70%).26

Treatment

The management of genital gonorrhea and chlamydia in adolescents involves prompt treatment with antimicrobial agents not only to eliminate symptoms and transmission risk, but also to prevent complications that occur when these organisms ascend to the upper reproductive tract as seen with PID or epididymitis (e.g., tubo-ovarian abscess, infertility, and ectopic pregnancy risks). In addition, management includes the prompt treatment of sexual partners and extensive patient education and risk-reduction counseling.

Current antibiotic regimens for treating uncomplicated C. trachomatis and N. gonorrhoeae genital infections are presented in Table 44–5. These are based on recommendations published by the CDC in its 2006 Sexually Transmitted Diseases (STD) Treatment Guidelines.27 It is important to remember that these are guidelines for infections of the lower reproductive tract. Antibiotic regimens for infections ascending to the upper tract (e.g., uterus, fallopian tubes, epididymis) are different. The management strategies for PID are discussed in Chapter 43.

Chlamydia Trachomatis

A 7-day course of doxycycline is a relatively inexpensive and highly effective form of therapy for chlamydia cervicitis and urethritis (>95% cure rate).17 However, the single-dose treatment with azithromycin allows for on-site or in-office treatment. This can be particularly helpful when treating adolescents, for whom patient compliance or confidentiality issues may prevent successful completion of a longer antibiotic course at home. In addition, azithromycin is the preferred antibiotic when treating pregnant adolescents, given the risks of doxycycline to a developing fetus.

Neisseria Gonorrhoeae

For cervical and urethral infections with N. gonorrhoeae, the CDC's 2006 STD Treatment Guidelines recommend the single-dose treatment options found in Table 44–5. However, the treatment of gonorrhea has become more complicated since the guidelines were published because of increasing resistance of N. gonorrhoeae to fluoroquinolones. Quinolone-resistant N. gonorrhoeae, previously a concern primarily outside the United States,30,31 has become more common in the United States. and higher rates were initially found in Hawaii and California, as well as among men having sex with men.32,33 However, data from the CDC-sponsored Gonococcal Isolate Surveillance Project34 has demonstrated increasing resistance patterns in other geographical areas and demographics across the United States. As a result, the 2006 Treatment Guidelines included a statement that “quinolones should not be used for the treatment of gonorrhea among men having sex with men or in areas with increased Quinolone-resistant N. gonorrhoeae prevalence in the United States or for infections acquired while traveling abroad.” This recommendation was most recently updated in April 2007 based on additional Gonococcal Isolate Surveillance Project data demonstrating even higher rates of Quinolone-resistant N. gonorrhoeae in heterosexual and homosexual populations in the United States. Currently, the CDC “no longer recommends the use of fluoroquinolones for the treatment of gonococcal infections and associated conditions” such as PID.35 This leaves the cephalosporins as the mainstay of gonorrhea treatment. Because cefixime is not readily available in the United States at this time,36 intramuscular administration of ceftriaxone is now the primary management option.

Because of the high frequency of concomitant chlamydia infection, it is often recommended that gonorrhea (GC) treatment also include empiric antibiotic coverage for Chlamydia unless testing shows no coinfection.37,38

Other Management Strategies

Patients should notify any sexual partner from the preceding 60–90 days (or the most recent partner if >60 days) of their infection and encourage them to seek evaluation and treatment as well. Patients should be advised to avoid sex until treatment (of themselves and their partner) is complete. The risk of coinfection with other STIs such as human immunodeficiency virus (HIV) should be discussed with adolescents. In addition, health care providers should help teenagers develop strategies (such as use of barrier contraceptives, routine screening, or abstinence) to prevent future exposure to these infections. It is recommended that treated patients be rescreened in 3 months to check for reinfection. NAATs can remain positive for either of these organisms for 3 weeks following treatment so retesting should be delayed for at least a month with this method.

Epidemiology

Over 170 million new cases of trichomoniasis occur annually worldwide.39 Nearly 8 million of those cases are in the United States, with approximately 2 million cases annually in the adolescent population.5 Manifesting as vaginitis in women and urethritis in men, prevalence estimates range from 2% to 3% in the general adolescent and young adult population40 to 17–54% among attendees of STI clinics.41–43 Much of the available data on trichomoniasis comes from female populations. Because of problems with detection methods, diagnosis can be difficult, particularly in males, and is, therefore, likely underestimated in both sexes.

Pathogenesis

Trichomoniasis results from infection with the organism, T. vaginalis. T. vaginalis, an anaerobic parasitic protozoan transmitted through genitourinary secretions, adheres to mucosal surfaces in the urogenital tract. It is classically described as a pear-shaped eukaryotic organism approximately 7 × 9 μm in size.44 Four anterior flagella, along with an undulating membrane with an embedded fifth flagellum, give the parasite mobility and may contribute to host cell damage. Adhesion to vaginal and urethral epithelial cells, damaging effects of hydrolases, local cellular immune responses, and production of cytotoxic molecules are other mechanisms of pathogenesis contributing to the mucosal inflammation caused by infection.44,45 Infection can be detected within 2 days of sexual contact, with a typical incubation period of 4–28 days. Infections can go undetected for a long time, sometimes persisting in women for months to years in epithelial crypts and periurethral glands.46 Infections with T. vaginalis have been associated with preterm rupture of membranes, preterm delivery, low birth weight, pelvic inflammatory disease, and an increased risk of acquiring HIV (facilitated by local inflammation and breakdown of the genital mucosal barrier).42,47–51

Clinical Presentation

Approximately one-half of women with trichomoniasis are symptomatic, while most infected men (>90%) have no symptoms at all.39,44 When symptoms are present in adolescent females, they are consistent with the vaginitis and urethritis caused by T. vaginalis (see Table 44–6). These include a vaginal discharge, vulvar itching, and dysuria. The discharge is typically characterized as yellow–green, watery, and malodorous. Because vulvar pruritus may be the patient's only complaint, many health care providers may miss the diagnosis of trichomoniasis by assuming the presence of a candidal infection (a common cause of vaginal itch) and treating empirically with an antifungal agent. Symptoms encountered by infected males usually reflect a urethritis, with dysuria being the most common complaint. It is thought that 11–19% of nongonococcal urethritis in males can be attributed to infection with T. vaginalis.41,44,52

Physical and speculum examination findings in women may include vulvar erythema and a frothy yellow–green vaginal discharge. A rarely seen but often described finding is colpis macularis, which represents punctuate hemorrhages in cervical epithelium that give the appearance of a “strawberry cervix.”53 Little has been described for physical findings in men, as they are rarely present.

Differential Diagnosis

When a genital infection with T. vaginalis is suspected, it is important to also consider the diagnoses listed in Table 44–3. In addition to trichomoniasis, non-STIs, such as candida and bacterial vaginosis (overgrowth of Gardnerella vaginalis and other anaerobes) also involve a shift in vaginal flora resulting in discharge and irritation. A nonspecific vaginitis can result from chemical irritants (such as perfumed soaps, bubble baths, and douching), poor hygiene, retained foreign body (e.g., tampon, condom), tight-fitting clothes, aggressive scrubbing of the vagina or vulva with washcloths, or the use of intravaginal contraception (e.g., Nuva Ring).54,55 If symptoms are present in an adolescent male, other causes of urethritis should be considered (see Table 44–3).

Diagnosis

The most commonly used diagnostic tool to detect trichomoniasis is microscopic examination of vaginal fluid. Diagnosis is made upon visualization of motile trichomonads on saline wet mount, as can be seen in Figure 44–1. A cotton-tipped swab is used to sample the posterior fornix of the vagina during a speculum examination. If a speculum examination is difficult to perform or not otherwise indicated, a blind vaginal swab (by the provider or the patient herself) will also suffice.56,57 To maintain the viability of the protozoa, the swab should be placed immediately into a test tube with a few drops of saline and then spread onto a glass slide for microscopic evaluation as soon as possible (preferably within 10 minutes).44 The active movement of the organisms or their beating flagella helps distinguish trichomonads from the many white blood cells likely to populate the microscopic field. Unfortunately, the sensitivity of saline wet prep is low, with reports in symptomatic women varying from 42% to 70% (and even lower if no symptoms).43,44,58,59 Therefore, the absence of visible trichomonads does not exclude the diagnosis and very often leads to undertreatment of this STI. Additional diagnostic findings when examining vaginal fluid include an elevated pH (>4.5), white blood cells on wet prep, and, occasionally a fishy odor after mixing with 10% KOH (the positive “whiff test” resulting from release of amines and more commonly seen with bacterial vaginosis). Although examining a concentrated first-void urine for motile trichomonads in males is possible, this is an extremely insensitive test to use and therefore not recommended. The same holds true for microscopic evaluation of male urethral swabs. Diagnosis of trichomoniasis in males is, therefore, usually made presumptively based on symptoms or by having sexual contact with a partner known to be infected.

Other point-of-care tests for T. vaginalis include a rapid antigen detection test (OSOM Trichomonas Rapid Test [Genzyme Diagnostics, Cambridge, MA]) and a nucleic acid probe test (Affirm VP III [Becton Dickenson, Sparks, MD]), which produce in-office results in 10 and 45 minutes, respectively. These tests are useful if a microscope is not available. They have a higher sensitivity (over 80% on vaginal specimens) than saline microscopy, with a slightly lower specificity (95–98% vs. 100%), but are less readily available.43,44,60–62

Trichomonas culture is considered the current “gold standard” for diagnosis of trichomoniasis. A commercially available culture method (InPouch TV test; BioMed Diagnostics, San Jose, CA) involves the inoculation of liquid growth medium in a prepackaged clear pouch that is examined under direct microscopy serially over 5 days. Vaginal swabs and male urethral swabs and first-void urine can be used with this technique. While more sensitive than the aforementioned tests (∼95%, with >95% specificity),58,63,64 results are not available for a few days, thereby delaying diagnosis.

With sensitivity >95% and specificity of 99%, newer PCR technologies to identify T. vaginalis in urine and vaginal fluid may help increase identification and treatment of this often underdiagnosed STI, especially in asymptomatic adolescents.65,66 However, no FDA-approved PCR test for trichomoniasis is currently available in the United States.

Treatment

The only class of drugs deemed useful for the treatment of trichomoniasis is the nitroimidazoles. Metronidazole 2 g in a single oral dose is the preferred regimen. Alternative regimens using metronidazole or tinidazole can be found in Table 44–7. Metronidazole is 90–95% effective in treating the infection.27 Patients should be forewarned of metronidazole's metallic taste and potential for GI upset, and should be discouraged from taking the medication on an empty stomach. Although adolescents are below the legal drinking age, they are known to experiment or use alcohol. Patients should, therefore, be warned of the disulfiram-like effects of metronidazole and advised to avoid alcohol for 24–72 hours posttreatment.27 Although intravaginal metronidazole gel is used for the management of bacterial vaginosis, it is far inferior to oral regimens in the treatment of trichomoniasis, especially when the urethra or paravaginal glands are infected.27 Topical therapies are therefore not recommended.

As discussed in the previous section on gonorrhea and chlamydia, the treatment of trichomoniasis should also include extensive counseling of adolescents about partner notification and treatment, avoidance of sex until treated, risks of coinfection with other STIs, and future prevention strategies.

Epidemiology

Over 100 genotypes of HPV have been identified by PCR analysis, of which over 30 types are transmitted sexually.67 Generally, HPV types can be subdivided into those that cause genital and mucosal lesions (e.g., condyloma acuminata) and those that cause nongenital cutaneous lesions (e.g., palmar and plantar warts).68 Genital lesions include anogenital warts, mild to high-grade changes in cervical epithelium, and (much less commonly) cancers of the cervix, vulva, anus, and penis.

HPV is the most common STI in the United States, affecting up to 20 million Americans aged 15–49.5 Recent estimates show prevalence rates of 24.5% among females aged 14–19 years and 44.8% among women aged 20–24 years. Similar numbers have been found in males, although prevalence rates of symptom-free genital HPV infection among males is not well established.69 Approximately, 9.2 million sexually active youth aged 15–24 years are currently infected with genital HPV, with over 4 million new infections detected in 2000.5 Risk of acquisition increases with the number of lifetime sexual partners and with earlier age at first sexual intercourse.70

Pathogenesis

HPV is most commonly acquired during penetrative intercourse (vaginal or anal sexual contact) by direct inoculation of the virus into the epidermal layers through microdefects in the epithelial layer. Other types of genital contact (i.e., oral–genital) can lead to transmission but are much less common. Sexual activity is the best predictor of acquiring HPV. The greater the number of sexual partners and the sexual activity of that partner, the higher is the risk of HPV infection.71 Another important risk factor is related to the large area of active immature metaplasia at the cervical transformation zone. In addition, genital infections can be transmitted vertically from mothers to newborns via passage through the birth canal producing respiratory papillomas, though this is rare.

Most genital HPV infections are transient in immunocompetent patients, as they are spontaneously cleared by the body's host defenses. It has been elucidated that cell-mediated immunity is the key component in clearing HPV infections.72 Patients with cell-mediated immunodeficiencies such as HIV have more frequent and severe HPV disease.

HPV types are characterized by their oncogenic potential. The major clinical conditions associated with HPV types involved in genital infections are listed in Table 44–8. Low-risk HPV types cause genital warts and benign or low-grade cervical epithelium changes, but are rarely found in association with invasive cancers. High-risk HPV types are associated with a range of changes in cervical epithelium that range from mild to high-grade dysplasia, as well as anogenital cancers. Based on the evidence from 11 case-control studies by the International Agency for Research on Cancer, 15 HPV types have been identified as high-risk types, and 12 categorized as low-risk types.73

Clinical Presentation

Condyloma acuminata (anogenital warts) is the most common presentation of genital HPV infection. The majority is benign and most commonly attributable to infection with HPV type 6 or 11. Condyloma acuminata can present as exophytic, papillomatous growths, but may also be small, discrete, sessile, smooth-topped papules or nodules. Color ranges from flesh-colored to reddish brown in appearance. Patients are most often asymptomatic, but they can experience pruritus, pain, and bleeding. Multiple sites are often involved, so it is necessary to inspect the entire lower genital tract, perineum, and anus. Common locations include the introitus, vulva, perineum, penis, and perianal areas. These warts may regress spontaneously or persist on the skin.

Differential Diagnosis

Other diagnoses that may be confused with genital warts include molluscum contagiosum (which often has central umbilication), syphilitic condyloma lata (distinguished by dark-field microscopy and positive syphilis serology), benign skin tags, verrucous carcinoma, and benign penile pearly papules.68

Diagnosis

The diagnosis of genital warts is primarily clinical, made by visual inspection. For lesions harder to detect, such as those on the cervix, diagnosis can be aided by the application of 5% acetic acid solution. Within minutes, condylomata appear as white patches. However, this technique has high false-negative and false-positive results.74 Biopsy is reserved for unclear circumstances.

Treatment

Although benign, genital warts are often cosmetically unacceptable to the patient and may enlarge if left untreated. An extensive assortment of pharmacologic and nonpharmacologic treatments is available, with no definitive first-line therapy. Treatments can remove warts in most patients, but recurrences are frequent.

Patient- and provider-administered therapies are presented in Table 44–9. Patient-administered therapies include podofilox 0.5% solution or gel (an antimitotic agent that disrupts cell division) and imiquimod 5% cream (which stimulates the innate cell-mediated immune response). Both of these applications require a several-week application, and can induce local reactions, such as erythema and swelling.

Common provider-administered therapies include trichloroacetic acid or bichloroacetic acid, which cause coagulation of proteins and may require weekly administration until resolution. Cryotherapy with liquid nitrogen, surgical excision, CO2 laser treatment, and electrocautery are other destructive therapies utilized. Most of these treatments have been associated with clearance or significant reduction in lesions, with roughly equivalent recurrence rates.27 Choice of primary therapy is dependent on location and size of lesions, patient preferences, provider skill and experience, and cost.

Cervical Cell Abnormalities

Although the primary focus of the HPV discussion in this chapter is on genital warts, it is important to recognize the cervical implications of this virus for adolescents. Although infection of the cervix with high-risk HPV is common in young sexually active patients, the infection is usually transient. The virus is undetectable in 70% of patients within 1 year of infection and in 91% within 2 years of infection. Persistence of high-risk HPV is necessary for progression of disease to invasive carcinoma.75 The American College of Obstetricians and Gynecologists (ACOG) recommends starting annual cervical cytology screening (i.e., Papanicolaou smear) 3 years after initiating sexual intercourse, but no later than age 21. The recommendation to wait 3 years after initiating sexual intercourse is to provide opportunity for clearance of transient HPV infections and prevent overtreatment of low-grade lesions.

While cervical cancer is exceedingly rare in the immunocompetent adolescent population, the main goal of screening is to detect, follow, and treat high-risk type HPV. According to the recent ACOG published guidelines, aggressive management of benign lesions in adolescents should be avoided because most cervical intraepithelial neoplasia (CIN grades 1 and 2) regress spontaneously.76 Refer to the ACOG guidelines for further details.

Prevention

In June 2006, a new quadrivalent HPV vaccine, Gardasil® (Merck & Co., Inc., Whitehouse Station, NJ), was approved by the Food and Drug Administration.77 This vaccine protects against the four HPV types primarily responsible for genital warts (types 6 and 11) and cervical cancer (types 16 and 18). The vaccine is administered through a series of three intramuscular injections over a 6-month period (0, 2, and 6 months). The Advisory Committee on Immunization Practices (ACIP) recommends use of the vaccine in females aged 9- to 26-year old.78 A bivalent vaccine that protects against HPV types 16 and 18 is expected in the near future.79

Ideally, the HPV vaccine should be administered prior to sexual activity, as it will only protect against those HPV types not yet acquired by the patient. However, sexually active women should also be offered this vaccine, since we do not know to which individual strains a women has been previously exposed. Currently, there is not enough data in men to support use of vaccine, but studies are ongoing. Duration of vaccine prevention is unclear, but current studies show effectiveness for at least 5 years.78 Although this vaccine could dramatically reduce the morbidity and mortality of HPV-associated diseases, it does not replace other prevention strategies, such as cervical cancer screening or protective sexual behaviors.