Article

Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study

Department of Family and Community Medicine, Center for Healthcare Policy and Research, University of California Davis, Sacramento, CA 95817, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 06/2009; 101(10):721-8. DOI: 10.1093/jnci/djp089
Source: PubMed

ABSTRACT

Information on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations.
We retrospectively identified 37,142 women treated for CIN 1, 2, or 3 from January 1, 1986, through December 31, 2000 (CIN cohort), from the British Columbia Cancer Agency cytology database and linked their records with cancer registry and vital statistics data. Treatment included cryotherapy, loop electrosurgical excision procedure, cone biopsy, and laser vaporization or excision. A comparison cohort contained 71,213 women with normal cytology and no previous CIN diagnosis. Follow-up continued through December 31, 2004. Among women in both cohorts under active surveillance, we compared rates of CIN 2 or 3 (CIN 2/3) and cervical cancer. Cumulative incidence rates of CIN 2/3 and 95% confidence intervals (CIs) were estimated by a life table approach by using annual rates. Cumulative rates of invasive cancer were examined by the person-years method.
Overall observed cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI = 13.84% to 14.15%) for women originally treated for CIN 3, 9.3% (95% CI = 9.09% to 9.42%) for CIN 2, and 5.6% (95% CI = 4.91% to 5.21%) for CIN 1. Annual rates of CIN 2/3 were less than 1% after 6 years. Initial diagnosis, age, and treatment type were associated with a diagnosis of CIN 2/3 after treatment, with 6-year adjusted rates for women aged 40-49 years ranging from 2.6% (95% CI = 1.9% to 3.4%) for treatment of CIN 1 with the loop electrosurgical excision procedure to 34.0% (95% CI = 30.9% to 37.1%) for treatment of CIN 3 with cryotherapy. Overall incidence of invasive cancer (per 100,000 woman-years) was higher in the CIN cohort (37 invasive cancers, 95% CI = 30.6 to 42.5 cancers) than in the comparison cohort (six cancers, 95% CI = 4.3 to 7.7 cancers). Cryotherapy, compared with other treatments, was associated with the highest rate of subsequent disease (adjusted odds ratio for invasive cancer = 2.98, 95% CI = 2.09 to 4.60).
Risk of CIN 2/3 after treatment was associated with initial CIN grade, treatment type, and age. Long-term risk of invasive cancer remained higher among women treated for CIN, particularly those treated with cryotherapy.

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    • "Recurrence rates of CIN 2–3 at 12 months seemed to be lower with CKC than with LEEP on the basis of two RCTs[32,33](RR 0.53; 95% CI 0.14–1.98), and also on the basis of data from seven nonrandomized studies[23,26,31,35363738(RR 0.66; 95% CI 0.36–1.20). Three RCTs[21,32,38]showed a probable reduction of major bleeds with CKC (RR 0.79; 95% CI 0.24–2.60). "
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    ABSTRACT: Cervical intraepithelial neoplasia (CIN) stage 2–3 is a premalignant lesion that can progress to cervical cancer in 10–20 years if untreated.
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    • "No cases of invasive squamous or adenocarcinoma were recorded during the long-term follow-up. The most used treatment modality was loop electrosurgical excision procedure (LEEP), personalized and performed by highly experienced personnel; the 8.8% rate of residual/recurrent high-grade lesions was at the lower end of the 5–30% published rates [4] [20]. The risk to develop invasive cervical disease in women treated for a high-grade lesion has been reported to persist for many years [5] [6] [21]. "
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    ABSTRACT: Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4-14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). Results. CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31-15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07-36.9), CIN3+ excision (OR 6.02, 95% CI 1.73-20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8-62.6; OR for other hrHPV types: 18.3, 95% CI 5.9-57.0). Conclusion. Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6-12 months of follow-up.
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    • "Failure can take the form of residual or recurrent CIN or invasive cervical cancer. One study reported that in the first 6 years after treatment, recurrence rates of CIN2/3 were 14.0% for women originally treated for CIN 3 and 9.3% for CIN 2, while incidence of invasive cancer was 37 per 100,000 woman-years in the cohort treated for CIN compared to 6 per 100,000 woman-years in the comparison cohort [69]. The ASCCP guidelines indicate followup with HPV DNA testing at 6–12 months or with cytology at 6-month intervals, with colposcopy recommended for women who are HPV-positive or have a repeat cytology result of ASC-US or worse [60]. "
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    ABSTRACT: Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.
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