A Study of 10 296 Pediatric and Adolescent Papanicolaou Smear Diagnoses in Northern New England

DISCUSSION

HPV is considered the most common sexually transmitted infection in both the adolescent and the adult patient.^7,,8 The prevalence of HPV, however, is difficult to determine because of the varied methods for detecting the virus, which include both direct nucleic acid detection and DNA amplification techniques. In addition, different studies have used probes to different types of HPV. Reported prevalence rates for HPV in the adolescent population range from 13% to 38%.^5,9–12 Despite this broad range in prevalence of HPV, it is clear that HPV infection is a very significant sexually transmitted disease in the adolescent population.

Epidemiologic and laboratory data strongly support the association of HPV infection with precancerous SIL¹³ and cervical cancer.¹⁴ It has been estimated that between 17% and 40% of patients with molecular evidence of HPV infection will have SIL^12,,15 and that as many as 80% of patients with cervical cancer have evidence of the HPV genome within the cancer as documented by either Southern hybridization or polymerase chain reaction.¹⁶

The rates of SIL reported in the adolescent population are complicated by differences in age groupings. For example, in our study, if we graphed our data in 5-year groups, the 20- to 24-year-old group would have the highest percentage of SIL. Clustered by decade, however, the 10- to 19-year-old population shows the highest percentage of SIL (Fig 2, A, B). Although this difference between 10- to 19-year-old groups and 20- to 29-year old groups is not statistically significant (P = .1), the high rates of SIL in both age groups are of clinical significance.

The distribution of the grades of SIL lesions on colposcopic biopsies from adolescents with abnormal Pap smear results (14% normal; 42% SIL low grade; 44% SIL high grade) was found to be similar to those in the adult population in a study by Jones and co-workers,¹⁷with the exception that no cases of invasive carcinoma were diagnosed in the adolescent group. Economos et al¹⁸ found that 13% of the adolescents (age 14 to 19 years) with abnormal Pap smear results had histologically proven SIL high grade. In our study, which involved only cytologic diagnosis of SIL, 18% of SIL smear results had evidence of SIL high grade, 65% SIL low grade, and 17% SIL grade uncertain.

The majority of the SIL diagnoses in our adolescent population were in the low-grade category (254 cases), representing 66% of the SIL cases. This finding is of clinical significance because patients with SIL low grade are at substantially increased relative risk (more than 16-fold) of developing SIL high grade and invasive cervical carcinoma compared with the SIL-negative population.^19,,20 Although most SIL low-grade lesions regress completely, the absolute risk of patients with SIL low grade for developing a SIL high grade within 2 to 4 years is 15% to 25%.¹⁴ Furthermore, SIL high grade may arise in a HPV-infected patient without an intervening diagnosis of SIL low grade.²¹

The largest study of this nature in the United States was reported 15 years ago by Sadeghi and associates,²² who found a 1.9% SIL rate in 194 069 sexually active adolescents (15 to 19 years of age), a figure that is less than our finding of 3.89%. In a study by Schydlower²³ of 9602 patients 12 to 21 years of age, 3% had SIL. Our data, grouped in the same manner as Schydlower's, would yield a 4.0% rate. The population studied by Sadeghi was from Cancer Screening Services in North Hollywood, CA, and thus most likely comprised urban and rural adolescents, whereas the study by Schydlower was of a military population. Despite the differences in demographics, our study of predominantly white rural and suburban adolescents suggests an increased incidence of SIL in this age group compared with these previous studies.

The explanation for this increase in SIL diagnoses is complex and hypothetic. Perhaps it reflects an increase in sexual behavior in this population. Increased detection with annual Pap smear screening and/or changes in viral types and frequencies of sexually transmitted HPV over the past decade also may contribute to the increase in diagnosis.

The ASCUS diagnoses, although calculated in this study, are more difficult to evaluate. Although patients with ASCUS diagnoses are at increased risk for the development of SIL,²⁴ the significance of this diagnosis remains, as its name suggests, “undetermined.” Furthermore, ASCUS diagnoses represent the area of most intraobserver variability among cytopathologists.^24–26 The ASCUS/SIL ratio of 2.6%, however, is similar to that for adult patients at our institution.

AGUS lesions in the adolescent patient have yet to be studied in any large cohort. The Bethesda System category of AGUS includes cells of adenocarcinoma in situ as well as cells suspicious for adenocarcinoma of the cervix, which now accounts for 8% to 26% of primary cervical cancers in adults.²⁷

The 14.6% rate of infectious processes, excluding HPV, was highest in the 10- to 19-year-old age cluster and when studied in 5-year groupings, showed the highest percentage in 10- to 14-year-old girls (16.7%) (Fig 3). The 10 to 19 age cluster showed the highest percentage rates of shift in flora, herpes, and fungus (Fig 4). Although not life-threatening, many of these microbiologic entities necessitate medical intervention.

The performance of a pelvic examination in sexually active adolescent girls is included in the American Academy of Pediatrics recommendations for Preventive Pediatric Health Care.²⁸ This recommendation states further that a pelvic examination and routine Pap smear should be offered as part of preventive health maintenance to patients between 18 and 21 years of age. The value of Pap smear examination in the sexually active adolescent continues to elicit debate as the medical economic climate forces reevaluation of many procedures previously considered routine.^29–32

Our study demonstrates that Pap smear results from 10- to 19-year-old patients in a rural and suburban setting have the highest percentage of SIL diagnoses (3.7%) and the highest percentage of infectious processes (14.6%) of all decade groupings. The high percentage of abnormal Pap smear results reported in this study is compelling evidence for the importance of periodic cervical Pap smear screening in the pediatric and adolescent population. Based on this and other studies, we recommend strongly that sexually active girls 10 to 19 years of age undergo yearly Pap smear screening.