Repeated studies have shown that adolescents remain one of the highest risk groups for HPV infection. A recent meta-analysis of studies throughout the world show that most countries demonstrate the same pattern with a peak in women under 25 years of age and a steady decline afterwards.3
Underscoring the vulnerability of young women to cervical HPV infection, studies of young women who recently initiate sexual intercourse show that half will acquire HPV within 2–3 years.4–6
Rates of HPV in adolescents, however, do vary; some populations show rates as low as 5% in adolescents with no decline or increase over time.3
The high rates of HPV reported in most adolescent populations have been attributed to either sexual behavior or biologic vulnerability. It remains unclear whether adolescents are more vulnerable to HPV because of their risk behaviors or if there is a true biologic vulnerability. Likely, both contribute.
Certainly, risks for HPV in adolescents are similar to those of adult women and include new sexual partners and lack of condom use.5,7,8
Most studies show that adolescents have more sexual partners than adult women and are worse users of condoms.9
One study showed herpes simplex virus (HSV) infection as an independent predictor of HPV acquisition as well.7
It is plausible that inflammation associated with HSV may contribute to the risk but presence of HSV may also reflect risky behavior.
Structurally the adolescent cervix is different from the adult's in that is has greater areas of immaturity described as a predominance of columnar and metaplastic epithelium. () This topography starts during embryologic development.10
In a brief review, the cervix is initially lined by Müllerian columnar epithelium and later replaced by urogenital squamous epithelium from the vagina towards the endocervical os in utero
. This results in an abrupt squamous-columnar junction located on the ectocervix in the neonate. This junction remains intact until puberty when hormonal changes trigger uncommitted generative cells of the columnar epithelium to transform themselves into squamous epithelium in a process referred to as squamous metaplaisa. Eventually, the replacement results in a new squamo-columnar junction occurring well into the os as seen in older women. This area of transition is referred to as the transformation zone. This area is also known as the site most vulnerable for cancer development.
Typical adolescent cervix. The cervix is primarily covered by a mixture of columnar and metaplastic tissue.
It is thought that this epithelium may itself be vulnerable to HPV. First, columnar epithelium is a single layer thick, hence, basal cells which is the presumed target for HPV are quite accessible. An example of the fragility of this area is the common presence of blood when Pap smears are obtained in adolescents with large areas of ectopy. Studies of HPV comparing age groups show that incident infections remain more common in young women even when controlling for recent sexual behavior. Munoz et al11
examined the incidence of HPV in women who were normal cytologically and HPV negative at entry. The incidence of HPV was highest in adolescents aged 15–19 years of age with a cumulative incidence of 17% at 1 year and 35.7% at 3 years. The rates declined with age: for women in the 20–24 year old group, the 3 year incident rate was 24.1% and for women 45 years and older it fell to 8.1%. Although this data supports the notion that adolescents may be biologically vulnerable, it may also suggest that the male sexual partner of the older women is less likely to carry HPV decreasing the chance of infection. Because of either behavior or biologic vulnerability, repeated infections in adolescents and young women are also common12,13
Second, the process of metaplasia itself may support viral replication. HPV requires cell replication and differentiation for it to complete its life cycle.14
Metaplasia, by definition is a process of cell replication and differentiation and hence perfect environment for HPV replication. Hence, exposure to HPV during times of active metaplasia is more likely to result in an established infection. In one study, adolescents with evidence of active metaplasia were more likely to show LSIL if infected with HPV.15
The high rates of squamous metaplasia in young women are likely the explanation for the high rates of LSIL seen in this population. LSIL is found most commonly in adolescents16
. This is supported by the observation that some countries see a second peak in HPV prevalence in women over 55 years of age, yet LSIL does not reflect this second peak with rates remaining under 1% in the older women.16
Differences in immune responses may also explain these differences. Unfortunately, little is known about the adult let alone the adolescent cervical mucosal immune response to HPV and questions remain as to whether these differ or not from adults. One study found that levels of IL-10 were much higher in adolescents with large areas of ectopy compared to those with mature cervixes.17
IL-10 is considered a Th-2 type cytokine which may favor HPV infection and persistence. Hormonal differences may also play a role.18
Since adolescents have frequent anovulatory menstrual cycles, unopposed estrogen may also have effects on the immune response. The consequences of these high rates of HPV in adolescents may be concerning. Several studies have shown that initiating sex at a young age is a risk for cervical cancer.19,20
Whether the risk is reflective of a high risk partner or whether it's related to a biologic risk remains unknown. Other factors such as C. trachomatis
infections may play a role in increasing adolescent vulnerability. C. trachomatis
which is also most common in the adolescent age group has been shown to enhance HPV persistence.21