Costa S, Venturoli S, Negri G, Sideri M, Preti M, Pesaresi M, et al. Factors predicting the outcome of conservatively treated adenocarcinoma in situ of the uterine cervix: an analysis of 166 cases. Gynecol Oncol 124: 490-5

Department of Obstetrics and Gynecology, S.Orsola-Malpighi University Hospital, Bologna, Italy.
Gynecologic Oncology (Impact Factor: 3.77). 12/2011; 124(3):490-5. DOI: 10.1016/j.ygyno.2011.11.039
Source: PubMed


The present study assessed the clinical outcome of patients conservatively treated for cervical adenocarcinoma in situ (AIS) and their predictive factors using univariate and multivariate population averaged (PA) generalized estimating equation (GEE) model in a longitudinal setting.
A series of 166 consecutive women (mean age 39.8 yrs; range 23-63 yrs) underwent conservative treatment of AIS as the primary treatment and were followed-up (mean 40.9 mo) using colposcopy, PAP-smear, biopsy and HPV-testing with Hybrid Capture 2.
Hysterectomy was performed as part of the primary management in 47 patients, who were excluded from the follow-up (FU) analysis. Out of 119 women closely followed-up, additional therapeutic procedures were performed in 69. At study conclusion, 7 patients (5.9%) showed persistent disease, while 8 (6.7%) had progressed to invasive adenocarcinoma (AC). Positive HR-HPV test was the only independent predictor of disease recurrence (adjusted OR=2.72; 95%CI 1.08-6.87), and together with free cone margins (OR=0.20; 95%CI 0.04-0.92), HR-HPV positivity was also the single most powerful predictor of disease progression to AC, with OR=3.74; 95%CI 1.84-7.61 (p=0.0001) in multivariate PA-GEE.
These results suggest that testing HR-HPV positive at any time point during FU is the most significant independent predictor of progressive disease, while showing free margins in cone has a significant protective effect against progression to AC. Furthermore, because 4.3% women with persistent, recurrent or progressive disease experienced a late (5th and 6th FU) diagnosis of HG-CGIN or microinvasive AC, a close surveillance should be scheduled for at least three years in conservatively treated AIS patients.

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    ABSTRACT: INTRODUCTION: The adenocarcinoma of the uterine cervix accounts for 10 to 20% of the premalignant and malignant lesions and is different from the cervical intraepithelial neoplasia and invasive squamous cell carcinoma. MATERIALS AND METHODS: Recent literature review (from 1985 to 2012) based on the literature available. RESULTS AND DISCUSSION: Adenocarcinoma in situ is an induced HPV lesion (role of HPV 18) of the glandular epithelium: its preferential endocervical situation explains the difficulties in the diagnosis and follow-up after conservative treatment. If the hysterectomy remains the gold standard for treatment, the conservative treatments (resection in sano of the lesions with margins of more than 1cm, meticulous study of the operative specimen, compliance with the follow-up) are possible in the young patients who desire to preserve their fertility. The invasive adenocarcinoma is characterized by a more difficult diagnosis because of its endocervical development, and a prognosis less favorable when compared to squamous cell carcinoma with a greater frequency of the lymphatic node involvement and metastatic diffusion. Its treatment must take into account the particular gravity of the factors of worse prognosis (FIGO stage, tumor size, lymphatic node spreading, adenosquamous histological subtype) in particular in the advanced stages and includes beside the surgery, radiotherapy and chemotherapy.
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    ABSTRACT: Adenocarcinoma in situ (AIS) of the uterine cervix is caused by infection with high-risk human papillomavirus and is the recognized precursor of invasive adenocarcinoma of the cervix. Because most AIS lesions are caused by HPV 16/18 infection, prophylactic HPV vaccination is an important step toward prevention of AIS, potentially reducing the incidence of invasive adenocarcinoma. Nonetheless, at the moment the incidence of AIS and invasive adenocarcinoma continues to increase, especially among young women when fertility preservation is an issue. Both diagnosis and treatment of AIS is challenging, because AIS lesions frequently extend into the endocervical canal, making detection and complete excision difficult. Hysterectomy remains the standard treatment for AIS. Selected patients, who wish to preserve fertility, with clear margins and negative ECC after initial conization are potential candidates for conservative treatment. If margins are involved after initial conization or ECC results are positive, the risk of residual or recurrent AIS and invasive adenocarcinoma of the cervix is considerably high. In these women, repeat surgery should be performed. For women, who do not undergo hysterectomy, long-term follow-up is recommended.
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    ABSTRACT: Objective: Cervical adenocarcinoma in situ (AIS) is increasing in incidence among reproductive-age women. Cervical conization is an alternative to hysterectomy that allows future fertility, however reports regarding the risk of residual AIS and underlying adenocarcinoma are conflicting. The purpose of this study was to determine the outcomes of a large cohort of women treated for AIS. Methods: The medical records of 180 women with cervical AIS evaluated at the University of Texas MD Anderson Cancer Center and its outlying clinics between 1983 and 2011 were reviewed for demographic information, treatment history, pathologic findings and outcomes. Results: The mean age at diagnosis was 33.8years (range 17.6-76.1years). 172 of the 180 women had at least one cone biopsy performed, with 110 (64.0%) undergoing a cold knife cone (CKC), and 62 (36.0%) undergoing a loop electrosurgical excision procedure (LEEP) as their initial method of treatment. Positive margins were noted in 35.0% of patients undergoing CKC compared with 55.6% undergoing LEEP (p=0.017). 71 patients ultimately underwent hysterectomy with residual disease noted in 10 patients (14.1%), 8 patients (11.3%) with residual AIS and 2 patients (2.8%) with invasive carcinoma. Of the 101 patients who did not undergo hysterectomy, 2 patients (2.0%) developed recurrent AIS at a median of 27.5months (range 18-37months) from the last cone, and none developed invasive carcinoma. Conclusion: Patients undergoing conservative management for AIS with cervical conization alone should be monitored closely and counseled regarding the potential risks of residual and recurrent disease, even when negative cone margins are obtained.
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