Active surveillance of cervical intraepithelial neoplasia grade 2 is not associated with an increased risk of noncervical anogenital human papillomavirus-related cancer and precancer: a population-based cohort study.
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BACKGROUND: In recent years, many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option in younger women with cervical intraepithelial neoplasia grade 2 instead of excisional treatment. This is mainly due to the high regression rates of cervical intraepithelial neoplasia grade 2 and the observed increased risk associated with excisional treatment. Women with a previous history of excisional treatment for cervical precancer are at an increased risk of subsequent anogenital cancer and precancer. For a full assessment of the benefits and harms of active surveillance for cervical intraepithelial neoplasia grade 2, we investigated the risk of noncervical anogenital cancers and precancers in women undergoing active surveillance. OBJECTIVE: We aimed to investigate whether women undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are at an increased risk of vulva, vaginal, or anal cancer and precancer compared to women treated with loop electrosurgical excision procedure. STUDY DESIGN: We conducted a nationwide population-based cohort study in Denmark. We included all female residents diagnosed with incident cervical intraepithelial neoplasia grade 2 at age 18 to 40 years from 1998 to 2020. The primary outcome was vulva, vaginal, or anal cancer or precancer. We stratified by age at cervical intraepithelial neoplasia grade 2 diagnosis (<30 years and ≥30 years), calendar year (1998-2012 and 2013-2020), and index cytology (nonhigh-grade and high-grade). As a secondary outcome, we considered low-grade lesions of the vulva, vagina, and anus. We used Cox regression to estimate hazard ratios of the outcomes with loop electrosurgical excision procedure as the reference group. We used inverse probability treatment weighting to calculate adjusted hazard ratios, considering age, calendar year, and index cytology as confounders. RESULTS: Overall, 27,505 women with cervical intraepithelial neoplasia grade 2 were included; 12,507 (45.5%) underwent active surveillance and 14,998 (54.5%) underwent loop electrosurgical excision procedure. A total of 162 women had a subsequent diagnosis of vulva, vaginal, or anal cancer or precancer. The cumulative risk after 10 years was 0.5% (95% confidence interval, 0.3-0.6). We found no difference in risk between women undergoing active surveillance and those having a loop electrosurgical excision procedure (adjusted hazard ratio, 1.00 [95% confidence interval, 0.71-1.40]). Similar findings were observed when stratifying by age, year of diagnosis, and index cytology. We found that the risk of low-grade lesions of the vulva, vagina, and anus was lower in women undergoing active surveillance than in women treated with loop electrosurgical excision procedure (adjusted hazard ratio, 0.75 [0.62-0.91]). CONCLUSION: Active surveillance for cervical intraepithelial neoplasia grade 2 is not associated with an increased risk of noncervical anogenital cancer and precancer compared to loop electrosurgical excision procedure. This finding contributes to the assessment of the benefits and harms of active surveillance and is useful for clinical counseling of women diagnosed with cervical intraepithelial neoplasia grade 2.