Pere Fusté

Does human papillomavirus infection imply a different prognosis in vulvar squamous cell carcinoma

BACKGROUND Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy. METHODS All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n=98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16(INK4a) expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazards model. RESULTS HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16(INK4a) stained 100% HPV-positive and 1.3% HPV-negative tumors (p<.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5 years; p=.831), or OS (67.2% vs. 71.4% at 5 years; p=.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III-IV (p=.002), lymph node metastasis (p=.030), size ≥ 20 mm (p=.023), invasion depth (p=.020) and ulceration (p=.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61). CONCLUSIONS HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women.

Value of p16INK4a as a marker of progression/regression in cervical intraepithelial neoplasia grade 1

OBJECTIVE The objective of this study was to evaluate the usefulness of p16(INK4a) staining to classify cervical intraepithelial neoplasia grade 1 according to its progression/regression risk. STUDY DESIGN Patients with a histologic diagnosis of cervical intraepithelial neoplasia grade 1 were prospectively recruited (n = 138). Simultaneous detection of high-risk human papillomaviruses and p16(INK4a) evaluation were performed. Follow-up was conducted every 6 months by cytology and colposcopy and annually by high-risk human papillomavirus testing, for at least 12 months (mean, 29.0). Progression was defined as a histologic diagnosis of cervical intraepithelial neoplasia grades 2-3, regression as a negative cytology and high-risk human papillomaviruses, and persistence as a cytologic result of low-grade squamous intraepithelial lesions and/or a positive test for high-risk human papillomaviruses. RESULTS Progression was observed in 14 women (10.1%), 66 (47.6%) regressed, and 58 (42.0%) had a persistent disease. p16(INK4a) was positive in 77 (55.8%) initial biopsy specimens. Progression to cervical intraepithelial neoplasia grades 2-3 was identified in 14 of 77 (18.2%) women with positive and none of 61 (0.00%) women with negative p16(INK4a) immunostaining (P < .001). CONCLUSION p16(INK4a) negative cervical intraepithelial neoplasia grade 1 lesions rarely progress and may benefit from a less intensive follow-up.

HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis

Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)‐negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV‐negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV‐negativity.

Transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR): A new method for sentinel lymph node detection in endometrial cancer

OBJECTIVE The objective of this prospective study was to determine the feasibility, safety and performance of a new method for sentinel lymph node (SLN) detection in endometrial cancer (EC) using transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR). METHODS From 2006 to 2011, 74 patients with high-risk EC were included in the study. Twenty-four hours before surgery 148MBq of (99m)Tc-nanocolloid (8mL) was injected into two spots in the anterior and posterior myometrium using an ultrasound-guided transvaginal puncture. SLN was localized preoperatively by lymphoscintigraphy and intraoperatively with gamma probe. After SLN biopsy the patients underwent a complete laparoscopic pelvic and paraaortic lymphadenectomy. RESULTS The TUMIR method was successfully achieved in 67/74 patients (90.5%). SLN was identified in 55 women (74.3%). No adverse effects were observed. Pelvic drainage was observed in 87.2% of women and paraaortic SLN was identified in 45.4%, with 12.8% of the patients draining only in this area. The mean number of SLN retrieved was 2.8 per patient (range 1 to 9). Metastatic disease was found in 13 (23.6%) patients. Metastatic involvement of the paraaortic lymph nodes was observed in 4 (30.7%) cases. All were identified by TUMIR. The sensitivity and negative predictive value of SLN detected by TUMIR to detect metastasis were 92.3% (95% CI 22.9-100) and 97.7% (95% CI 82.0-100), respectively. CONCLUSIONS TUMIR is a safe, feasible method to detect SLN in patients with EC, has a good detection rate and provides representative information of the lymphatic drainage of EC.

Comparative study of laparoscopically assisted radical vaginal hysterectomy and open Wertheim-Meigs in patients with early-stage cervical cancer: eleven years of experience.

Introduction: The aim of this study was to compare the feasibility, safety, and survival outcomes of Coelio-Schauta (CS) procedure versus open Wertheim-Meigs (WM) as primary surgical treatment of early-stage cervical cancer. Methods: Observational study on the consecutive cases of cervical cancer undergoing CS during the last 11 years at our institution was performed. Data on clinical characteristics of patients, surgical performance, long-term morbidity, and survival were prospectively analyzed and compared with a historical series of 23 consecutive WM performed at the same hospital in the immediate previous period. Results: Sixty-seven patients were included in the study group (CS). Cases and controls were comparable in age, body mass index, stage, tumor size, and histological diagnosis. The number of pelvic nodes, disease-free margin, and complications rate were similar in both groups, but blood loss and blood transfusion rate were marginally less in the CS group. Operating time was longer in the first 20 CS patients, but it became comparable to WM once the learning curve was overcome. Hospital stay was significantly shorter in the CS group as well as the bladder function recovery time. However, no differences were seen regarding long-term urinary and bowel function between groups. Four patients (5.9%) from the CS group and 3 (13%) in the WM group had recurrence. Mortality rates were 3% and 8.7%, respectively (P = not significant). Conclusions: The CS procedure is a suitable alternative to WM for small-volume, early-stage cervical cancer, showing a good safety profile, shorter postoperative recovery time, and similar survival outcomes.

Treatment of endometrial hyperplasia without atypia in peri- and postmenopausal women with a levonorgestrel intrauterine device.

Objective: To assess the effectiveness of the Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) in peri- and postmenopausal women with endometrial hyperplasia without atypia. Design: All consecutive women with histologically documented endometrial hyperplasia without atypia recruited during a 1-year period participated in an open, prospective, single-center study. They were followed for at least 2 years after levonorgestrel-releasing intrauterine system insertion. The pattern of uterine bleeding was evaluated on a 4-point qualitative scale (1 = amenorrhea, 2 = scarce, 3 = normal, 4 = abundant). Results: The study population consisted of 15 women with a mean (SD) age of 49 (2.7) years. Compared with baseline, bleeding decreased quantitatively from a mean score of 3 at baseline (normal bleeding) to 2 (scarce) at 3and 6 months, and 1 (amenorrhea) at 24 months. Endometrial biopsies performed at 12 months revealed atrophicendometrium in 14 women (93.3%) and secretory endometrium in 1 (6.7%) (P < 0.001). At 24 months, endometrial atrophy was documented in 100% of women. Conclusions: The levonorgestrel-releasing intrauterine system seems to be an effective and safe alternative in the treatment of peri- and postmenopausal women with (simple) endometrial hyperplasia without atypia.

Human papillomavirus detection in urine samples: an alternative screening method.

Objectives. To investigate the usefulness of human papillomavirus detection in the urine of women with poor gynecologic attention. Materials and Methods. Fifty urine and 50 cervical samples from 50 women were analyzed. Polymerase chain reaction was performed on these 100 samples using consensus primers and a low-density microarray-based method for human papillomavirus typing. Results. The concordance of the results between both sample groups was 80%. In the urine samples, the sensitivity of polymerase chain reaction for high-grade squamous intraepithelial lesion was 100%, the specificity was 80%, the positive predictive value was 91%, and the negative predictive value was 100%. Conclusions. Human papillomavirus detection in urine samples may be used as an alternative screening method for women with poor gynecologic attention.

Ganglio centinela en cánceres ginecológicos. Nuestra experiencia

UNLABELLED Although sentinel lymph node (SLN) identification is widespread used in melanoma and breast cancer some concerns exist in other malignancies, such gynaecologic cancers, and this staging method has not been adopted in many centers due to lack or large validation studies. AIM To evaluate the applicability and results of SLN technique in gynaecological malignancies referred to our institution. METHOD We studied 155 patients with different malignancies (70 vulvar, 50 cervical and 35 endometrial cancers). The day before surgery a lymphoscintigraphy was performed by injecting 111 MBq of (99m)Tc-nanocolloid in several ways depending on the type of cancer studied. Intraoperative detection of the SLN was always performed by using a hand-held gammaprobe and, in 100 cases with the aid of blue dye injection (70 vulvar and 30 in cervical cancer) few minutes before surgical intervention. Pathological study of SLN was performed in all cases. Lymphadenectomy was done in all cervix and endometrial cancer patients and in the first 35 vulvar cancer patients. RESULTS Pre-surgical lymphoscintigraphy demonstrated one, at least, SLN in 97% of vulvar cancer patients, 92% in the cervical malignancy and 64% in the endometrial cancer patients. During surgery, SLN was harvested in 97%, 90% and 62% of patients, respectively. The pathological study showed metastases in 24.2%, 8.8 and 4.5% of patients with vulvar, cervical and endometrial cancer, respectively. The false negative percentage was 5.5% in vulvar cancer patients, with 2 cases in the endometrial cancer and without any case in the cervical cancer patients. CONCLUSION Lymphoscintigraphy is a relatively simple and useful technique to identify the SLN in this kind of tumours. However, in endometrial cancer more effort has to be made to reach a suitable result. Sentinel lymph node biopsy seems to be a reliable technique in vulvar and cervical malignancies.

Predictors of absence of cervical intraepithelial neoplasia in the conization specimen

OBJECTIVE Over 10% of women who undergo conization for cervical intraepithelial neoplasia (CIN) show no lesion in the surgical specimen. We aimed to determine whether these patients can be identified before conization using clinical, virological and/or cyto-histological characteristics, to avoid unnecessary treatment. METHODS Of 687 women with CIN treated by conization in the Hospital Clinic of Barcelona between 2008 and 2011, all patients (n=110, 16%) showing no lesion in the surgical specimen were included as the study group. The control group included a series of randomly selected women with CIN in the cone specimen (n=220). Pre-conization clinical characteristics as well as high-risk human papillomavirus (hr-HPV) status determined by Hybrid Capture 2 were analyzed as possible predictors of absence of lesion. RESULTS A negative pre-conization hr-HPV test or a low viral load (<10 relative light units) significantly increased the probability of absence of CIN in the conization specimen (75.0%, and 52% respectively) compared with patients with a high viral load (26.7%, p<0.001). This association was confirmed in the multivariate analysis (p<0.001). The risk of developing persistent/recurrent disease after treatment was significantly lower in patients with negative hr-HPV test or a low viral load (16.1% CIN1, 0% CIN2-3), than in patients with a high viral load (27.6% CIN1, 4.1% CIN2-3, p=0.031). CONCLUSION Women with negative pre-conization hr-HPV test results or a low viral load have a high probability of having no lesion in the conization specimen. These patients should be excluded from immediate surgical excision and considered for follow-up.

Hpv Determination in the Control After Leep Due to Cin Ii-iii: Prospective Study and Predictive Model

To evaluate the usefulness of the endocervical cytology immediately after loop electrosurgical excision procedure (LEEP) and viral human papilloma virus (HPV) determination as predictive factors of persistence/recurrence (P/R) of squamous intraepithelial lesion (SIL) in the remaining cervix of patients treated with LEEP due to cervical intraepithelial neoplasia (CIN) II or III. We retrospectively selected 105 samples from 100 patients with histologic diagnosis of CIN II-III with cytology immediately after LEEP with a first control post-LEEP between 2 and 6 months after treatment that included HPV determination, a minimal follow-up period of 12 months and maximum of 24 months, and at least 2 colpocytologic controls post-LEEP. In 71 of the 105 patients (67.6%), the determination was negative, finding the presence of HPV in 34 patients (32.4 %). Almost two-thirds of the patients had negative endocervical cytology and absence of HPV. During the follow-up, 20 P/R were detected, 16 (15.2%) of them being high-grade squamous intraepithelial lesions (7 CIN II and 9 CIN III). The combination of endocervical cytology and HPV determination in the remaining cervix seems to be a good strategy to predict the risk of SIL after conization. The probability of P/R can be estimated based on the results of these 2 variables. The negativity of HPV determination together with a negative endocervical cytology guarantees enough security and a favorable evolution.