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

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.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment—Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology

“…Unlike squamous lesions, glandular cervical disease usually has a worse prognosis and a higher recurrence rate [ 8 ]. Our results reported a recurrence rate within the range of what is reported in the literature (7.1%) [ 6 , 7 , 21 , 22 , 23 , 24 ]. As mentioned, in situ/microinvasive AC of the uterine cervix represents the majority of cervical glandular lesions and can be treated conservatively.…”

“…Sample size calculation was performed using the estimation of a confidence interval with a required width for a single proportion based on the study’s primary outcome: recurrence rate in situ/microinvasive ACs. The literature reports a range of disease relapses between 2 and 14% [ 6 , 7 , 21 , 22 , 23 , 24 ]. We expected a mean value of 8%.…”

Predicting the recurrence of usual-type cervical adenocarcinoma using a nomogram based on clinical and pathological factors: a retrospective observational study

“…Belkic et al. found that HPV-18 positivity during follow-up was the greatest predictor of recurrence in a cohort of 84 women with cervical adenocarcinoma in situ, with an odds ratio of 141 ( 19 ). HPV-18 positivity is reportedly the best predictor of recurrence (p<0.005).…”

“…Positive HPV findings in two cases predicted recurrence (p<0.02). HPV-18 and prolonged HPV positivity are highly predictive of recurrence ( 19 ).…”

Faktor Risiko Kekambuhan Lesi Prakanker Serviks Pasca Pengobatan Tinjauan Literatur

“…Hal tersebut didasari atas fakta bahwa lesi prakanker serviks yang telah ditangani dapat muncul kembali atau disebut dengan kekambuhan. Berdasarkan keseluruhan literatur yang ditinjau, diketahui bahwa tingkat kekambuhan atau recurrence rate lesi prakanker serviks berkisar antara 6,1% hingga 21,69% (Alder et al, 2020;Belkić et al, 2022;Bittencourt et al, 2023;Bogale et al, 2022;Ding et al, 2023;Ge et al, 2021;Kulkarni et al, 2023;Pambinkavil et al, 2023;Zeng et al, 2022). Lebih dari 50% kekambuhan terjadi kurang dari dua tahun pasca pengobatan lesi prakanker serviks (Fernández-Montolí et al, 2020).…”