HPV testing as an effective triage strategy in the follow-up after fertility-sparing treatment for glandular lesions of the uterine cervix.

OBJECTIVE: The management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing. METHODS: We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months). RESULTS: In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7-179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank). CONCLUSION: Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.

Local control after tailored surgical treatment of early cervical cancer.

BACKGROUND: It was the aim of our study to analyze oncological outcome and prognostic parameters in patients with early stages cervical cancer after tailored and well-standardized surgical treatment with an adequate follow-up. METHODS: Oncological outcome and prognostic parameters were evaluated in a group of 192 patients with cervical cancer stages IA2 to 2B who had undergone radical hysterectomy (n = 171), radical parametrectomy (n = 12), or radical trachelectomy (n = 9). Procedures were classified as type B (n = 72), type C1 nerve sparing (n = 103), or type C2 (n = 17). RESULTS: Event-free and overall 5-year survivals probabilities reached 92.7% (confidence interval, 89.5%-95.9 %) and 94.1% (confidence interval, 90.9%-97.3 %). There was only 1 isolated pelvic recurrence found of the total of 10 recurrences. Adjuvant radiotherapy was given to only 22% of patients. The most significant independent prognostic parameters in stage IB tumors were lymph node status, histological type, and tumor volume, whereas in stage II, the parameters included histological type and tumor volume, the latter being inversely related to the prognosis. CONCLUSIONS: We have shown an excellent prognosis, especially local control, after tailored surgical treatment of stages IA2 to IIB of cervical cancer, with low prevalence of adjuvant treatment. Different prognostic parameters were observed for stages IB1/IB2 and IIA/B.

High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma.

BACKGROUND: Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. OBJECTIVE: The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2-IIIB tumours and correlate findings with histopathology. STUDY DESIGN: The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group. RESULTS: The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. CONCLUSIONS: Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort.

Abdominal radical trachelectomy in fertility-sparing treatment of early-stage cervical cancer.

BACKGROUND: Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. In comparison with vaginal radical trachelectomy, the published results of ART are so far limited. METHODS: Enrolled were women referred for ART either by laparoscopy or laparotomy. The main inclusion criterion was stage IA2 or IB1 with a cranial extent that allows for preservation of at least 1 cm of the endocervical canal. RESULTS: A total of 24 women were referred for the procedure, but fertility could not be preserved in 7 (29%) of them. Four women underwent immediate completion of radical hysterectomy because of a positive cranial surgical margin (n = 2) or sentinel node macrometastasis (n = 2) on frozen section. We found no correlation between tumor volume and inability to preserve fertility. A positive sentinel node was identified in 4 patients (17%); there were no false-negative results. Of the 9 women (53%) who have tried to conceive so far, 6 (67%) have conceived and 5 given birth, 2 of which were premature deliveries. CONCLUSIONS: Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy. The main criterion for the selection of suitable patients should be the cranial extent of the tumor. Abdominal radical trachelectomy allows for achievement of satisfactory obstetrical outcomes.

High-risk human papillomavirus DNA in the primary tumor, sentinel, and nonsentinel pelvic lymph nodes in patients with early-stage cervical cancer: a correlation with histopathology.

INTRODUCTION: Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early-stage cervical cancer. Still, approximately 15% of patients with negative pelvic nodes experience recurrence, most of them in the pelvis. The presence of human papillomavirus (HPV) DNA in histologically negative pelvic nodes is considered a subclinical metastatic spread. METHODS: Patients with early-stage cervical cancer referred for surgical treatment were enrolled in the study. Cytobrush technique was used for sample collection from the fresh tissue to avoid any loss of material for histology. RESULTS: Altogether, 49 patients were enrolled in the study. High-risk (HR) HPV DNA was identified in the tumor in 91.8% patients and in the sentinel node or other pelvic nodes in 49.9% patients. Among the 10 HR HPV genotypes detected, HPV 16 was the most frequently represented in both the tumor and the lymph nodes (66.7% and 71.4%, respectively). All metastatic lymph nodes were HR HPV positive. CONCLUSIONS: The presence of HR HPV DNA in a sentinel node had a 100% positive predictive value for metastatic involvement of pelvic lymph nodes in our study. This could be considered a sign of an early subclinical metastatic spread; however, the prognostic value has to be evaluated through a longer follow-up.