Author: Delese E. LaCour, MD*
Infections caused by human papillomavirus (HPV) result in considerable morbidity and mortality throughout the world.1–4 Conditions such as anogenital warts, caused by low-risk HPV genotypes and cervical dysplasia, more commonly caused by oncogenic HPV types, can affect females in all age groups.5–9 The prevalence of low and high risk HPV infection in females in the United States in 2003–2004 is 26.8%, estimated from the National Health and Nutrition Examination Survey.10 When analyzed by age group, the prevalence of HPV was 35% in females ages 14–19, 29% in ages 20–29, 13% in ages 30–39, 11% in ages 40–49, and 6.3% in ages 50–65.10,11
HPV is a nonencapsulated, double stranded DNA virus which can infect either cutaneous or mucosal surfaces.3,12 Over 200 types of HPV have been identified.13–15 Forty of those types are known to infect the anogenital tract14–17 and they are classified as low or high risk by their capacity to induce oncogenic changes.
HPV types that are unlikely to cause cancer include HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, and 72.1,18 High risk types HR-HPV are more commonly associated with cancers and include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82.2–4,7 In North America, HPV 16 and 18 account for 70% of cervical cancer.4,18
HPV infections can cause anogenital and oral lesions in adults as well as the very young. This paper will review the prevalence, transmission, persistence, and clinical manifestations of HR-HPV in very young children.
Mechanism of Action
Microabrasions in the surface epithelium permit the entrance of HPV into the cell where it targets the basal layer of the stratified squamous epithelium. The metaplastic cells of the squamocolumnar junction of the cervix and oropharynx are also targets.1–3
There are five phases in the HPV life cycle, they include (1) infection and uncoating, (2) proliferation, (3) genomic phase, (4) viral synthesis, and (5) shedding.19 In the first phase, infection and uncoating, the basal cells are infected by HPV.19 The second phase is genomic maintenance. During this phase, early viral proteins (E1 andE2) are expressed. The virus maintains its genomic material with a low number of copies (10–200 copies per cell).19 The proliferative phase follows and early proteins E6 and E7 are expressed. These proteins stimulate cell cycle progression and control regulation in the parabasal layer. Genomic amplification follows in the suprabasal layer and early proteins are expressed (E1, E2, E4, and E5). Viral synthesis then occurs and late proteins (L1 and L2) are expressed. In the epithelial layer, these structural proteins enhance viral packaging. At the stratified layer of the epithelium, the virus is released when dead cells are shed and the virus is then free to infect other cells. This infectious cell cycle is thought to occur over a period of time of two to three weeks.4 The incubation period can range from 1–20 months.6
Another possibility in the HPV life cycle is latency. After initial infection, the immune system can induce regression of the viral life cycle and the virus can remain in a latent stage in the basal epithelium (Fig. 1).19
Most infections with HPV are subclinical. In very young children (less than four years old), visible manifestations of HPV infection may include condyloma acuminatum.8 Cervical and anal infections in young children are the result of sexual abuse.9 Oral lesions include verrucae vulgaris, papillomas, condylomas, and focal epithelial hyperplasia.20–22 The majority of these lesions (75%) are the result of HPV 6 and 11. Juvenile onset recurrent respiratory papillomatosis (JORRP) is rare, more serious condition that can result is.21–24 Estimated to occur in 4.3/100,000 births, JORRP is caused by infection with HPV types 6 or 11 and is most likely to occur in first born, vaginally delivered children of women less than 20 years old.21,22,24,25