Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix: Up to 14 years of recorded follow-up

Karen Belkić; Sonia Andersson; Susanna Alder; Miriam Mints; David Megyessi

doi:10.3892/ol.2022.13477

Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix: Up to 14 years of recorded follow-up

Oncol Lett. 2022 Aug 25;24(4):357. doi: 10.3892/ol.2022.13477. eCollection 2022 Oct.

Authors

Karen Belkić^{1

2

3}, Sonia Andersson⁴, Susanna Alder⁴, Miriam Mints^{4

5}, David Megyessi⁴

Affiliations

¹ Department of Oncology-Pathology, Karolinska Institute, SE-17176 Stockholm, Sweden.
² School of Community/Global Health, Claremont Graduate University, Claremont, CA 91711, USA.
³ Institute for Health Promotion and Disease Prevention Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, USA.
⁴ Department of Women's and Children's Health, Obstetrics-Gynecology Division, Karolinska Institute, Stockholm, SE-17176 Stockholm, Sweden.
⁵ Department of Gynecology and Obstetrics, School of Medical Sciences, Faculty of Medicine-Health, Örebrö University, SE-70182 Örebrö, Sweden.

Abstract

The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.

Keywords: adenocarcinoma-in-situ; margin status; papillomavirus infection; treatment failure.

Grants and funding

The present study was supported by the Swedish Cancer Foundation (grant no. 110544; CAN2011/471), Karolinska Institute (Cancer Strategic Grants; grant no. 5888/05-722), Swedish Research Council (grant no. 521-2008-2899), Stockholm County Council (grant nos. 20130097 and 20160155) and Gustaf V Jubilee Fund (grant nos. 154022 and 151202).