title: Disparities in mean age and histopathologic grade between human papillomavirus type-specific early cervical neoplasms.
abstract: Noninvasive squamous and glandular precursor lesions associated with human papillomavirus (HPV) types 16 and 18 have been reported to vary in morphology. HPV 16 is associated predominantly with high-grade squamous intraepithelial lesions (HSIL; cervical intraepithelial neoplasia (CIN 2 and 3), and HPV 18 is associated with low-grade squamous intraepithelial lesions (condyloma/CIN 1) and CIN 3/adenocarcinoma in situ (ACIS). This study explored the relationship of morphologic growth pattern in these precursor groups with age of presentation. One hundred fourteen CIN lesions (including those with ACIS), associated with HPV 16 or 18, were subdivided into well-differentiated low- and high-grade SIL (CIN 1 and 2, respectively), poorly differentiated HSIL (CIN 3) with or without ACIS. HPV was detected by polymerase chain reaction (PCR) amplification with L1 consensus or type-specific E7 primers and typed by restriction fragment length polymorphism (RFLP) analysis. Age of the patient was obtained from the pathology report. Mean age for each group was as follows: Low-risk HPVs, 25 years; HPV 18 CIN 1-2, 21.6 yrs; HPV 18 CIN 3/ACIS, 35.2 yrs; HPV 16 CIN 1,2, 25.9 yrs; and HPV 16 CIN 3, 29.8 yrs. There were significant differences in mean ages between HPV 18 CIN 1 and 2 and HPV 16 CIN 1 to 2 (P = .04), HPV 16 CIN 1-2 and CIN 3 (P = .01) and HPV 18 CIN 1 to 2 and HPV 18 CIN 3/ACIS (P = .00001). None of the cases of HPV 18-associated CIN3/ACIS was associated with a CINI lesion. The disparity in mean ages between well and poorly differentiated HPV 16/18 related that precursor lesions could reflect factors such as morphologic progression with increasing age, different rates of lesion persistence, depending on grade, or efficiency of detection between the two groups. The marked difference in mean age between HPV 18-associated CIN 1-2 and CIN 3/ACIS, combined with their lack of coexistence in the same cervix, raises alternate possibilities that specific viral or host factors may determine the morphological phenotype associated with some HPV 18 infections. In the latter, the possibility that age independently confers an increased risk for higher-grade lesions should be considered.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston MA 02115, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: McLachlin
authors.forename: L H
authors.initials: LH
authors.lastname: Shen
authors.forename: E E
authors.initials: EE
authors.lastname: Sheets
authors.forename: H
authors.initials: H
authors.lastname: Kozakewich
authors.forename: S E
authors.initials: SE
authors.lastname: Perlman
authors.forename: J E
authors.initials: JE
authors.lastname: Tate
authors.forename: C P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002278:Carcinoma in Situ / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral