Viral Infections

Introduction
Herpes simplex virus (HSV) is discussed in detail in this articles -Herpes genital (genital Herpes simplex)Herpes Genitalis and Herpes simplex with a brief clinical description outlined in

Table 3-16.


Human Papillomavirus

Human papillomavirus (HPV) is a member of the Papovavirus family and is a closed, circular, double-stranded DNA virus. The viral genome is enclosed in an icosahedral capsule composed of several protein capsomeres and lacks the lipid-containing envelope common to many other viruses such as herpes simplex. Unlike other human STD virus infections such as herpes simplex, however, HPV growth in cell culture has been difficult because its replication is dependent on epithelial cell differentiation and maturation.

The common clinical presentation of HPV is the genital wart or external condyloma acuminatum. However, with the advent of DNA amplification techniques, it has become clear that HPV has extensive clinical expression ranging from latency to condyloma to invasive cancers, particularly of the anogenital tract. Subclassification of HPV into over 100 types has been based on differences in degree of DNA homology. Common skin warts are associated with types 2 and 4, whereas benign genital condyloma is usually associated with HPV type 6 or 11. In contrast, anogenital neoplasias are commonly associated with types 16, 18, 31, 33 or 35, 45, and 56.

Pathogenesis
The definitive mechanisms of HPV infection are unclear. The HPV appears to require direct access to basal epithelial cells to establish infection, and active cell division and differentiation are required for HPV replication. Vulnerable human sites where basal cells not only are physically accessible to viral inoculation but also are actively dividing include the active squamous metaplasia of the transformation zone of the female cervix and areas of wound healing in the genital area. In adolescents and young women, 70 to 90% of HPV infections are transient. On the other hand, persistent infection has been closely linked to the development of anogenital cancers. Recent information has linked several viral-host protein interactions with the loss of cell cycle control, a likely step in the development of these cancers. The natural progression from infection to cancer is not well understood. However, cofactors thought to play important roles include HSV, hormonal influences, cigarette smoking, and altered immunologic responses to infection or injury.

Clinical Syndromes
The HPV can cause multicentric disease including much of the anogenital area: the vaginal introitus, vulvar labia minora and majora, clitoris, perineum, anus, and cervix in women; and the penis, including the prepuce, frenulum, corona, glans, and shaft, with the anus and scrotum in men. The common genital warts, condyloma acuminatum, which are seen on the skin surfaces, present as polypoid masses with fissured and irregular surfaces. They are often multiple and polymorphic and commonly coalesce into large masses. When on mucosal surfaces, condyloma acuminatum appears as finger-like projections with central dilated capillary loops.

Subclinical infections are characteristically defined as lesions visualized with the aid of colposcopy and acetic acid. These include low-grade intraepithelial lesions (LSIL) and high-grade intraepithelial lesions (HSIL) and are typically identified by cytology screening. Typical appearances on colposcopy associated with LSIL, HSIL, and invasive cancers can assist in directing biopsy. Final diagnosis is dependent on histologic interpretation of the biopsy, not colposcopic appearance. Latent HPV DNA is also common in women, specifically young women. It is thought that this type of latency is transient in most. On the other hand, persistence of infection has been shown to be associated with a significant risk of HSIL and invasive cancer development.

Diagnosis and Treatment
Screening for HPV infections in adolescents is currently limited to visual inspection for external genital warts and cytology screening for LSIL, HSIL, and invasive cancers during the pelvic examination. Diagnosis of genital warts by visual inspection is considered adequate, and HPV testing plays little to no role in confirming the diagnosis unless the diagnosis is questioned. In this case, biopsy is the best confirmation. The differential diagnosis includes bowenoid papulosis, vulvar intraepithelial neoplasia, Bowen disease, condylomata lata, skin tags, nevocellular nevus, benign tumors, sebaceous glands, seborrheic keratosis, pearly penile papules, molluscum contagiosum, squamous cell carcinoma, vulva papillomatosis, and vestibular papillae. Treatment for genital warts includes primary ablative therapy including application of 85% trichloroacetic acid to the wart itself. Cryotherapy with liquid nitrogen is also quite effective. Treatments are usually applied weekly up to 4 to 6 weeks. If there is no improvement, therapy should be switched, or the diagnosis should be questioned. The current role of podophyllin resin in therapy is questioned because its potency is unpredictable, and it is contraindicated on mucosal surfaces and in pregnancy. Other methods include excisional and laser therapy. Self-applied therapies are also available and may be more cost-effective. Podofilox is applied directly to the warts twice daily for 3 consecutive days and repeated weekly up to 4 to 6 weeks. A recent novel therapy, imiquimod, which is a cytokine-inducing agent, appears to have equal efficacy as other therapies, and its advantage is the ability to self- apply treatment. Disadvantages to all therapies include irritation, inflammation, and ulceration from local applications.

Although cytology has known limitations in sensitivity, the primary screening tool for SIL and invasive cancers in adolescents remains cytology. Although HPV testing has recently been shown to help in SIL screening in older women, its role appears less specific in adolescents because of the high rates of HPV infections and LSIL and low rates of HSIL and invasive cancer in this age group. Currently, annual Pap smears are recommended in sexually active women. Pap smears in sexually inactive adolescents are not necessary.

Abnormalities on cytology, including a single HSIL, two LSIL, or two ASCUS on repeated cytologies, should prompt referral to colposcopy and biopsy. Confirmed HSIL by histology should be treated with either excisional therapy (LEEP) or cryotherapy. Lesions that are high into the endocervical canal may require conization. Confirmed LSIL may be observed with repeated Pap smears at 4- to 6-month intervals. Treatment is recommended for persistent LSIL at 18 months or if the lesion has progressed at any time to HSIL. Referral of partners to women with condyloma or SIL is controversial because most partners of women appear to have latent HPV infection. However, most agree that partners should be encouraged to have a genital examination by their physician for signs of infection. As with all STIs, examination should include tests for other co-sexually transmitted infections.

There are no treatments available or indicated for latent HPV infection.

Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) is the newest viral STD to infect youth. An in-depth description of its clinical syndrome, AIDS, is beyond the scope of this section. See HIV / AIDS Health Center for a detailed description of HIV infection.

Provided by ArmMed Media
Revision date: July 8, 2011
Last revised: by Sebastian Scheller, MD, ScD