Clinical Characteristics and Long-Term Follow-up of Patients Treated for High-Grade Vaginal Intraepithelial Neoplasia: Results From a 20-Year Survey in Italy.

OBJECTIVES: The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. MATERIALS AND METHODS: The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. RESULTS: Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. CONCLUSIONS: The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

Indication of prophylactic vaccines as a tool for secondary prevention in HPV-linked disease.

PURPOSE: To determine whether quadrivalent HPV vaccination is effective in reducing recurrent disease in women with a previous history of HPV disease. METHODS: All women under 45 years of age treated for HPV-linked disease and with negative HPV test, cytology and colposcopy 3 months after treatment were enrolled. Women were randomly assigned into two groups: a group that received HPV vaccine post treatment and a group that was only submitted to follow-up. Follow-up was performed every 6 months for a duration of at least 3 years. Kaplan-Meier curve was used to estimate the overall disease-free survival during the follow-up period. Statistical analysis was performed by Fisher's exact test. RESULTS: From November 2013 to October 2014, we enrolled a total of 178 women at Careggi University Hospital in Florence and at Azienda USL in Massa Carrara. 12 out of 89 patients in the non-vaccination group recurred (13.5%), while 3 out of 89 patients in the vaccination group recurred (3.4%). The Kaplan-Meier curves showed a statistically difference in the log rank test (p = 0.0147) for the overall disease-free survival in the study groups during follow-up. The rate of recurrence was significantly higher in the non-vaccination group, with a p = 0.0279 by Fisher exact test. CONCLUSION: The introduction of anti-HPV vaccination during the follow-up post treatment for HPV-linked disease is recommended to reduce the risk of recurrence. The clinical implication of this could be very important to influence post-treatment management of HPV disease.

Long-term reliability of fractioned CO2 laser as a treatment for vulvovaginal atrophy (VVA) symptoms.

PURPOSE: The aim of this study was to evaluate long-term effects of the fractional CO2 laser for the treatment of vulvovaginal atrophy (VVA) symptoms. METHODS: Women presenting with VVA symptoms and meeting inclusion criterion were enrolled to fractioned CO2 laser therapy. Patient's satisfaction was measured on five-point Likert scale at 4 weeks and 6, 12, 18, 24 months after treatment by interview and clinical examination for vaginal livability. RESULTS: 184 patients constituted the final study group: 128 women were spontaneous menopause and 56 were oncological menopause. 117 women were nulliparous and 36 had previous hysterectomy. 95.4% (172/184) of the patients declared that they were satisfied or very satisfied with the procedure at 4 weeks after treatment. At 6 months 92% (170/184) patients were satisfied; at 12 months 72% (118/162) were satisfied; at 18 months 63% (60/94) were satisfied; at 24 months 25% (4/16) of patients answered they were still satisfied. We observed a decline in patient's satisfaction between 18 and 24 months after laser therapy. Data showed that the time interval from onset of menopause was a statistically significant factor (p < 0.05) for treatment satisfaction in oncological group. CONCLUSION: Long-term data showed that the improvement of vaginal health may continue up to 24 months after fractional CO2 laser treatment although between 18 and 24 months benefits decline, and approximately 80% of women decide to start a new treatment cycle of laser applications.

Erratum to: Long-term reliability of fractioned CO2 laser as a treatment for vulvovaginal atrophy (VVA) symptoms.

In original publication, the Fig. 1 was incorrect. The correct figure has been given below.

Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors.

PURPOSE: The aim of this study was to evaluate the efficacy of fractional CO2 laser therapy in breast cancer survivors as a therapeutic method for vulvovaginal atrophy (VVA) dyspareunia. METHODS: 50 patients (mean age 53.3 years) underwent fractional microablative CO2 laser treatment for dyspareunia in oncological menopause (mean time of menopause 6.6 years). The Gloria Bachmann's Vaginal Health Index (VHI) score was chosen as system to evaluate the presence of VVA and its improvement after the treatment. Intensity of dyspareunia was evaluated using a visual analog scale (VAS). RESULTS: Data indicated a significant improvement in VVA dyspareunia (p < 1.86e-22) in breast cancer survivors who had undergone 3 sessions of vaginal fractional CO2 laser treatment. Moreover, VHI scores were significantly higher 30 days post-treatment (T4) (p < 0.0001). 76 % of patients were satisfied or very satisfied with the treatment results. The majority (52 %) of patients were satisfied after a long-term follow-up (mean time 11 months). No adverse events due to fractional CO2 laser treatment occurred. CONCLUSIONS: The treatment with fractionated CO2 laser appeared to be a feasible and effective treatment for VVA dyspareunia in breast cancer survivors with contraindications to hormonal treatments.

HPV-related cervical disease and oropharyngeal cancer.

Human papillomavirus (HPV), especially HPV 16, is associated with the development of both cervical and oral cancer. We show the case of a woman affected by HPV-related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41-year-old woman arrived at our Colposcopy Center following an abnormal Pap smear result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a cervical biopsy. She underwent a colposcopy that showed a cervical abnormal transformation zone grade 2. A laser conization was performed in November 2010. Histology reported a moderate/severe dysplasia. The cone resection margins were free. Follow-up colposcopy and cytology were negative. The HPV testing showed an infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A biopsy was performed with a result of squamous cell carcinoma with low-grade differentiation. The HPV testing detected a high-risk HPV and the immunohistochemical analysis was positive for p16. She was treated by chemotherapy and brachytherapy. She was followed at the head-neck center with monthly visits with oral visual inspection that showed complete absence of mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous lesions have significant similarities in terms of pathogenesis. They are both caused largely by HPV 16, as in the present case. In conclusion, because of this association found in literature and in our case, we think that women with HPV cervical lesions should have regular surveillance for oropharyngeal cancer, whereas women with OPSCC should be encouraged to have diligent cervical screening.

CO2 laser total superficial vulvectomy: an outpatient treatment for wide multifocal vulvar intraepithelial neoplasia grade 3.

The ideal treatment of large multifocal vulvar intraepithelial neoplasia grade 3 (VIN 3) in young patients is still debated. The goal is to prevent development of invasive vulvar cancer while preserving normal vulvar anatomy and function. The authors describe the case of a 37-year-old woman affected by a biopsy-proven VIN 3 involving the entire external genitalia. A total superficial vulvectomy was carried out in 2 closer sessions by CO(2) laser used in an excisional way. Both procedures were performed in an outpatient setting with the patient under local anesthesia and without suturing stitches or skin flaps. Definitive pathologic analysis confirmed VIN 3 with free margins. No intraoperative and postoperative complications were documented. Functional and anatomic outcomes were optimal, and no relapse occurred after 12 months of follow-up. Use of CO(2) laser total superficial vulvectomy shows promise of a safe and adequate treatment in selected young patients with VIN 3 involving the entire external genitalia.

High-risk HPV positivity is a long-term risk factor for recurrence after cervical excision procedure in women living with HIV.

OBJECTIVE: To evaluate the risk factors for recurrence of high-grade disease after cervical excision in women living with HIV (WLWH), with a specific interest in the role of high-risk (HR-) HPV positivity. METHODS: Multicentric retrospective study conducted on WLWH who underwent cervical excision between January 1987 and June 2017 in six Italian institutions. The rate of high-grade recurrence was determined. Risk factors for recurrence and HR-HPV positivity were determined with the Log-rank test and Cox proportional hazards regression models. RESULTS: A total of 271 WLWH were included in the final analysis. A high-grade recurrence was found in 58 (21.4%) patients. Age 41 years or more at inclusion and HR-HPV positivity during follow up were independently associated with a higher risk of disease recurrence with relative risks of 4.15 (95% confidence interval [CI] 2.01-8.58, P < 0.001) and 5.18 (95% CI 2.12-12.67, P < 0.01), respectively. Age 41 years or more (relative risk 1.75, 95% CI 1.01-3.04, P = 0.047) resulted as a risk factor for HR-HPV positivity during follow up. CONCLUSION: HR-HPV positivity is a risk factor for recurrence after cervical excision in WLWH. Women older than 41 years may benefit from a long-term yearly follow up. Future studies regarding HPV vaccination after treatment in WLWH may be useful, considering the protective role of the higher probability of HPV negativity in vaccinated women.

PCR detection rates of high risk human papillomavirus DNA in paired self-collected urine and cervical scrapes after laser CO2 conization for high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To compare the PCR detection rates of high risk human papillomavirus DNA in self-collected urine and cervical scrapes during follow-up of patients treated for HG-CIN by laser CO2 conization. PATIENTS AND METHODS: 52 women who submitted to laser conization for HG-CIN were enrolled into this prospective follow-up study receiving liquid-based cytology and HR-HPV testing by PCR assay on self-collected urine and cervical scrapes before and at 3, 6 and 12 months after treatment. Diagnostic accuracy and predictive values for treatment failure were evaluated for both urinary and cervical HPV testing and follow-up cytology. RESULTS: 3 cases (5.8%) of recurrent HG-CIN occurred during follow-up. Positive margins and HR-HPV persistence resulted to significant risk factors for recurrence (p=0.01). The overall concordance on HR-HPV detection between paired urine and cervical samples was 96.6% and discord trend between agreement rates during follow-up were excluded by overall fixed-effect index (OR 1.03; 95% CI 0.62-1.70). No difference was observed comparing the three- and six-month cumulative sensitivity and NPV for recurrent disease of urinary and cervical HPV detections, with an increase of 5.6% in specificity associated with urinary testing. CONCLUSIONS: PCR detection of HR-HPV in paired urine and cervical samples during follow-up revealed an excellent concordance, suggesting a potential equivalent role of the two methods within post-treatment follow-up. In our experience HPV testing on self-collected urine was more sensitive than cytology and more specific than cervical HPV detection to predict treatment failure. Larger studies are needed to definitively establish the role of urine-based HPV testing during follow-up.

CO2 laser cylindrical excision or standard re-conization for persistent-recurrent high-grade cervical intraepithelial neoplasia (HG-CIN) in women of fertile age.

AIM: To investigate the therapeutic efficacy of cylindrical or cone-shaped excision performed by laser CO2 in the conservative management of persistent-recurrent high-grade cervical intraepithelial neoplasia (HG-CIN) in women of fertile age. PATIENTS AND METHODS: Ninety-four premenopausal patients with persistent-recurrent HG-CIN had undergone re-conization or cylindrical excision according to the time of reappearance of the disease. The length of the procedures, intra- and postoperative complications, height of the excised specimens, final histological findings and follow-up data were retrospectively evaluated. RESULTS: Fifty-five (58.5%) persistent and 39 (41.5%) recurrent cases had undergone cylindrical excision and standard re-conization respectively. All the treatments were successfully performed in an out-patient setting under local anesthesia with no differences in term of operative time, height of removed specimens, intra- and postoperative complications between the two groups. Definitive histology confirmed HG-CIN in 95.7% of the cases and FIGO Stage Ia1 cervical cancer (negative lymph vascular space involvement, LVSI) in 4.3% of the cases. The endocervical margins were involved in 3.6% of the cylindrical (persistent) and in 17.9% of the cone-shaped (recurrent) specimens (p = 0.03). The overall cure rate after a median follow-up time of 54 months (range 10-196) was 91.5%. A third excisional procedure was performed in 8 cases of persistent-recurrent HG-CIN with a disease-free subsequent follow-up of 38 months (range 6-108). CONCLUSION: Cylindrical or conical re-excision performed by CO2 laser according to the time of reappearance of the disease seems to be a promising conservative approach for persistent-recurrent HG-CIN even though further randomised prospective studies are needed to confirm the long-term efficacy and reproductive outcomes.

Carbon-dioxide laser vaporization of the Bartholin gland cyst: a retrospective analysis on 200 cases.

STUDY OBJECTIVE: To evaluate the effectiveness of carbon-dioxide laser vaporization as definitive treatment for Bartholin gland cyst. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: University teaching hospital. PATIENTS: A consecutive series of 200 patients with monolateral or bilateral Bartholin gland cyst. INTERVENTIONS: A standardized technique of cyst vaporization performed by carbon-dioxide laser in outpatient setting and local anesthesia. MEASUREMENTS AND MAIN RESULTS: Records of all patients were reviewed for anamnestic information, anatomic parameters, intraoperative and postoperative outcomes, and follow-up data. Seven patients having bilateral cyst were treated in a single session; 207 procedures were performed. The cyst mean size was 6.3 +/- 2.3 cm (95% CI 5.93-6.67). All treatments were completed in outpatient regimen and local anesthesia with a median operative time of 17 minutes (range: 7-45). Three (1.5%) cases of intraoperative major bleeding were observed. The cure rate of a single laser treatment was 95.7%. The 9 patients with recurrent disease observed during follow-up underwent carbon-dioxide laser reintervention by the same therapeutic strategy with a 100% cure rate after 2 or 3 treatments. CONCLUSION: Carbon-dioxide laser vaporization of Bartholin gland cyst represents a safe and effective procedure with complete healing and positive follow-up outcomes. Further randomized trials should be conducted to confirm these findings and to establish the best surgical strategy.

Laser CO2 conization in postmenopausal age: risk of cervical stenosis and unsatisfactory follow-up.

OBJECTIVE: To assess chances of adequate cyto-colposcopic follow-up after laser conization performed in postmenopausal screening population by the evaluation of postoperative cervical stenosis and unsatisfactory colposcopy rates. PATIENTS AND METHODS: One thousand two hundred eighteen patients were submitted to laser CO2 conization for cervical intraepithelial neoplasia (CIN). Incidence and risk factors for cervical stenosis and unsatisfactory follow-up were retrospectively evaluated comparing fertile with postmenopausal patients. RESULTS: Global incidences of postoperative unsatisfactory colposcopy and cervical stenosis were 46.2% and 7.1%. These rates were higher in postmenopausal patients compared with fertile ones, revealing a statistical correlation between unsatisfactory follow-up and postmenopausal status at the time of conization. Association between CIN relapse and cervical stenosis was significantly higher in postmenopausal group (66.7% vs. 8.6%; P <0.05), where two cases of recurrence were detected only after hysterectomy, because of an insurmountable cervical stenosis. Univariate and multivariate analysis revealed HRT use as the only significant factor in influencing postoperative cervical stenosis. CONCLUSION: Conization is still considered as the standard treatment for CIN at any woman's age, when excisional management is indicated, but all postmenopausal patients should be counseled about the possibility of postoperative stenosis that could exclude an adequate follow-up, configuring a failure of the conservative treatment. HRT use is associated with a low risk of stenotic complications; therefore, if possible, users should be encouraged to continue therapy at least 1 year after laser conization.

Laser CO2 vaporization for high-grade cervical intraepithelial neoplasia: a long-term follow-up series.

OBJECTIVE: The goal of this study was to evaluate the effectiveness of laser CO(2) vaporization for conservative treatment of ectocervical high-grade cervical intraepithelial neoplasia (CIN) particularly by the evaluation of the reappearance risk of disease in long-term follow-up. METHODS: One hundred fifty-nine patients were submitted to CO(2) laser vaporization for high-grade CIN and followed up for a minimum of 5 years. Selection of cases, depth of ablation, complications, and cure rate (percentage of treated patients in whom there was no recurrent/persistent high-grade CIN at the 5-year follow-up examination) were retrospectively evaluated. RESULTS: Selected cases for colposcopy were submitted to a 6-mm mean depth of vaporization without intra- or postoperative complications. The cure rate for a single treatment was 97.5% and a satisfactory colposcopic follow-up was possible in 99.4% of treated patients. No case of invasive carcinoma occurred after a mean follow-up of 7.1 years. Four cases (2.5%) were high-grade CIN persistence observed after a mean time of 3.75 months, suggesting incomplete destruction of the deepest part of the lesion involving the glandular crypt base. CONCLUSIONS: Long-term follow-up proves that laser CO(2) vaporization still has a place in the treatment of CIN. In selected cases it represents a safe alternative for conization in the treatment of high-grade CIN, but colposcopic expertise is essential for adequate preoperative selection of cases.