Long-term risk of recurrent cervical human papillomavirus infection and precancer and cancer following excisional treatment.

Risk of recurrent CIN2+ (including cervical intraepithelial neoplasia grade 2 [CIN2], CIN3, carcinoma and in situ, adenocarcinoma in situ or cancer) remains elevated for years following treatment. The role of long-term post-treatment human papillomavirus (HPV) presence on subsequent risk of CIN2+ was evaluated in the 10,049-women Guanacaste cohort. Six hundred eighty-one women were referred to colposcopy because of high-grade cytology, positive cervicography and/or suspicion of cancer based on visual assessment; 486 were judged to require treatment. After excluding women with <12 months of follow-up (N = 88), prior cancer or hysterectomy (N = 37) or other reasons (N = 14), 347 were included in the analysis. Infections were categorized as persistent if present at both pre- and post-treatment visits and new if detected only post-treatment. Median time between the treatment and post-treatment visits was 6.7 years (interquartile range 3.8-7.8). At the post-treatment visit, 8 (2.4%), 2 (0.6%) and 8 (2.4%) of the 347 treated women had persistent HPV16, HPV18 or other carcinogenic HPV, respectively. Two (0.8%), 3 (1.0%) and 13 (4.0%) had new HPV16, HPV18 and other carcinogenic HPV, respectively. Six CIN2+ cases were identified at the post-treatment visit, all with persistent infections (three HPV16, one HPV18 and two other carcinogenic HPV). No recurrent disease was observed among women with new HPV infections during the follow-up period. Thus, persistence of HPV infection a median of six years after treatment was uncommon but, when present, posed a substantial risk of subsequent CIN2+. Serial follow-up data from other studies would further strengthen these conclusions.

Stability of archived liquid-based cervical cytologic specimens.

BACKGROUND: Exfoliated cervical cell specimens collected in PreservCyt, a methanol-based medium used in ThinPrep liquid-based cytology, have been archived in epidemiologic studies. However, long-term DNA stability and cytologic stability of these biospecimens have not been evaluated. METHODS: Cervical specimens were collected into PreservCyt from participants in a natural history study of human papillomavirus (HPV) infection and cervical carcinoma in Guanacaste, Costa Rica (1993-2000), and stored at ambient temperatures. Thirty specimens classified as low-grade squamous intraepithelial lesions by liquid-based cytology were randomly chosen from each collection year (except for 1994) and selectively assessed for molecular and cytologic stability. Specimens were tested in 2001 for 1) HPV DNA by the Hybrid Capture 2 test, 2) beta-globin DNA by polymerase chain reaction amplification of multiple length fragments (268, 610, and 1327 bp), and 3) nuclear preservation by visual inspection of newly made liquid-based cytology slides. All testing was done masked to year of collection. Associations of stability and storage time were evaluated using standard contingency tables and chi-square tests for trend. RESULTS: Human papillomavirus DNA, as detected by the Hybrid Capture 2 test, was unaffected by storage time. Stability of beta-globin DNA (P(Trend) < 0.0001) and nuclear preservation (P(Trend) < 0.0001) declined with increasing storage time. Approximately 15% of specimens could not be amplified for any beta-globin DNA fragment after 5 years of storage (collected in 1996). In addition, cytology slides made from 41% specimens were rated as marginal (32%) or unsatisfactory (9%) after 8 years of storage (collected in 1993). CONCLUSIONS: Cervical specimens archived in PreservCyt underwent partial DNA and cytologic degradation after several years of storage. Methodologic studies to optimize long-term storage of cervical cells for epidemiologic studies of cervical carcinoma are needed.