Imiquimod 5% cream versus cold knife excision for treatment of VIN 2/3: a five-year follow-up.

BACKGROUND: Vulvar intraepithelial neoplasia (VIN) is a premalingnant condition. For long time, surgery was considered the first-line therapy in the treatment of high grade VIN. Imiquimod was recently introduced as an alternative to surgery. AIM: To compare the overall complete response, the recurrence rate and the risk factors for relapse among patients with VIN 2/3 treated with Imiquimod or surgical excision. PATIENTS AND METHODS: Eighty women who had histological diagnosis of VIN 2 and VIN 3 were enrolled in this prospective study. Patients immunocompromised, with recurrent VIN, with well differentiated type VIN or VIN 1 and women treated more than once were excluded from the study. Patients were divided into two groups: group A was treated with Imiquimod, group B underwent surgical excision. Patients' characteristics analyzed were: age, smoking, degree of the primary lesion, state of margins, multifocal disease. We have evaluated the recurrence rate, the relapse rate, and the overall complete response, considering as recurrence the onset of a lesion after an initial complete response to Imiquimod and/or after the surgical treatment and as relapse all patients who had a recurrence plus those with medical treatment failure. RESULTS: Multifocal lesions (p = 0.03) and VIN 3 (p = 0.002) were associated with a higher risk of relapse. The recurrence rate was higher in the group B (p = 0.009), but the relapse rate was higher in the group A (p = 0.04). The overall complete response was better in the group B (p = 0.04). CONCLUSIONS: Although the advent of new medical options can decrease the morbidity associated with invasive surgical procedures, surgical treatments remain the best treatment modality for VIN with regard to relapse and overall complete response.

Teenagers' knowledge about HPV infection and HPV vaccination in the first year of the public vaccination programme.

The aim of this study was to assess teens' knowledge of HPV infection and vaccination one year after the initiation of the public vaccination programme and information campaign on the disease and the opportunity of vaccination. Between 15 May and 15 June 2009, a survey was carried out on 1,105 teenagers attending high schools in a town in the northeast of Italy by means of an anonymous and unannounced questionnaire covering the knowledge of HPV infection, transmission, prevention, vaccination and post-vaccination behaviours. Only 75% of teens knew what HPV infection is (92% of girls vs 51% of boys, p < 0.001); only 70% knew that it is a sexually-transmitted infection. Only 69.3% associated condoms with HPV disease prevention (72.6% girls vs 61.5% boys, p = 0.002). About 18.8% of girls and 33.2% of boys believe that HPV can lead to AIDS (p < 0.001). Among teens aware of HPV vaccination, 7.6% of girls and 21.8% of boys believe that it can prevent AIDS (p < 0.001). Only 75.5% of girls and 51.1% of boys (p < 0.001) believe that condom use remains useful for HPV prevention after vaccination. The need for regular pap smears after vaccination is reported by 93.3% of girls. Teens' knowledge about HPV infection and vaccination remains insufficient, despite a broad information campaign. Erroneous information may increase risky sexual behaviours. Without complete information about HPV infection and vaccination and information about other sexually-transmitted diseases, the latter might become difficult to control among teenagers, while some misunderstandings about the usefulness of secondary prevention might linger.

[Knowledge of HPV-related genital lesions and of anti-HPV vaccination in a sample of women of north-eastern Italy]. / Conoscenza delle patologie genitali HPV-correlate e sul vaccino anti-HPV in una popolazione femminile del nord-est italiano.

AIM: Knowledge of human papilloma virus (HPV) infection and related genital lesions and vaccine is related to the success of the vaccination program. Authors have assessed knowledge, attitudes and beliefs on HPV and vaccination in a sample of women, in order to optimize any educational interventions. METHODS: This study enrolled 212 consecutive women with no history of HPV-related genital lesions by means of an anonymous questionnaire. The questionnaire included 21 questions (19 with a multiple choice and 2 with open answers) to check awareness of HPV infection and related lesions, HPV transmission, vaccine and vaccination program expectations, sexual/precautionary behaviours after vaccination and the need felt for more information. RESULTS: Forty-two percent of women in the study population know about HPV-related genital lesions, and 43% are aware of the right way of transmission; 75% have learned about the vaccine. In this last group 28% know that the vaccine efficiency is mainly limited to the HPV types included in the vaccine, 19.8% know that one of the vaccines can also prevent genital condylomata and 88% have heard about this vaccination program. CONCLUSIONS: There is still a lack of information or access to information about HPV and more needs to be done to raise awareness of HPV vaccination. A percentage of 74.4 of women wish to receive more information and thinks that schools and family planning clinics should play a central role in teenagers' health education. There is a need to further train healthcare workers involved in the vaccination program in order to optimize their counselling to teenagers and parents.

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions.

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC). The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series. Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult "usual-type" AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5). In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7-206 months) and no cases of progression to HCGIN or AC were observed. In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients.

Trend of decreasing length of cervical cone excision during the last 20 years.

OBJECTIVE: The aim of the present investigation was to evaluate the cervical conizations performed in the last 20 years in a single institution, with a particular interest in analyzing the trend of the length of cone excisions. PATIENTS AND METHODS: A retrospective cohort study of women who underwent a CO2-laser cervical conization between January 1996 and December 2015. Cytological abnormalities on referral pap smear, colposcopic findings and pertinent clinical and socio-demographic characteristics of each woman were collected. In particular, the length of cone specimen was evaluated, taking into account all the factors potentially influencing the length of excision. RESULTS: A total of 1270 women who underwent cervical conization from January 1996 to December 2015 were included in the analysis. A mean cone length of 15.1 ± 5.7 mm was reported, and we observed a significant decrease in the length of cone excisions over the whole study period. Age (rpartial = 0.1543, p < 0.0001), see & treat procedure (rpartial = -0.1945, p < 0.0001) and grade II colposcopic findings (rpartial = 0.1540, p < 0.0001) were significantly associated with the length of cone excision on multivariate analysis. CONCLUSIONS: In the last 20 years, a significant decrease in the length of cone excision was observed. In our opinion, this can be due to the acquired awareness by the gynecologists of the potential disadvantages of wide cone excision in term of adverse obstetric outcomes in future pregnancies.

Colposcopic patterns of vaginal intraepithelial neoplasia: a focus on low-grade lesions.

OBJECTIVE: The aim of this study was to evaluate the colposcopic patterns observed in women with a histopathological diagnosis of vaginal intraepithelial neoplasia, with a particular interest in analyzing the colposcopic characteristics of low-grade squamous intraepithelial lesions (LSIL). PATIENTS AND METHODS: Medical charts and colposcopy records of women diagnosed with vaginal intraepithelial neoplasia from January 1995 to December 2015, were analyzed in a multicenter retrospective case series. The abnormal colposcopic patterns observed in women with vaginal LSIL and vaginal high-grade SIL (HSIL) were compared. The vascular patterns and micropapillary pattern were considered separately. RESULTS: Regardless the histopathological grading, in women with vaginal SIL, the grade I abnormal colposcopic findings were more frequent than grade II abnormalities. However, a grade I colposcopy was more commonly observed in women with a biopsy diagnosis of LSIL rather than HSIL (p<0.0001). Similarly, the micropapillary pattern was more frequently observed in women with LSIL (p=0.004), while vascular patterns were observed more frequently in women diagnosed with vaginal HSIL (p<0.0001). In women with grade I colposcopy, the menopausal status and a previous hysterectomy appeared to be associated with the diagnosis of vaginal HSIL. CONCLUSIONS: Grade I abnormal colposcopic findings were more commonly observed in women with vaginal LSIL, as well as the micropapillary pattern. On the other hand, grade II abnormal colposcopy and the presence of vascular patterns were more frequently observed in women with vaginal HSIL.

Suppressive role of the metastasis-related nm23-H1 gene in human ovarian carcinomas: association of high messenger RNA expression with lack of lymph node metastasis.

The nm23-H1 gene has been proposed as a metastasis suppressor gene. It is located on the long arm of chromosome 17, which is frequently deleted in ovarian cancer, and shows altered expression and structure in some advanced neoplasms. To evaluate the role of nm23-H1 in ovarian carcinogenesis, we have analyzed this gene in 66 primary human ovarian carcinomas at both the DNA and RNA levels. Despite the high frequency (76%) of nm23-H1 loss of heterozygosity (LOH), the complete absence of gene mutations in the coding portions of the retained allele clearly indicated that, in ovarian carcinomas, this gene does not function in the same way as do classic oncosuppressor genes. The relationship of clinicopathological parameters with nm23-H1 gene deletions and expression levels was also investigated. LOHs were more common in the serous and endometrioid histotypes (85 and 93%, respectively), and the highest LOH frequency was detected in poorly differentiated tumors (89%). A significant relationship between nm23-H1 mRNA expression and lymph node metastasis was observed in high-grade tumors, which are intrinsically more invasive than are low-grade tumors. In particular, among the poorly differentiated tumors showing areas of undifferentiated solid carcinoma (classified as G3/G4), lymph node-negative tumors displayed expression levels that were significantly higher than those of lymph node-positive tumors (P < 0.001). In conclusion, our data suggest that the nm23-H1 gene product may exert an inhibitory effect on the lymphatic dissemination of human ovarian tumors. However, several other factors, biological or time and patient dependent, influence the complex metastatic progression of ovarian tumors and may cooperate with nm23-H1 in the promotion or inhibition of this process.

High-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer: a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV).

OBJECTIVE: The aim of this study was to analyse the women with high grade vaginal intraepithelial neoplasia (HG-VaIN), in order to identify a subset of women at higher risk of progression to invasive vaginal cancer. MATERIALS AND METHODS: The medical records of all the women diagnosed with HG-VaIN, and subsequently treated, from January 1995 to December 2013 were analyzed in a multicentre retrospective case series. The rate of progression to invasive vaginal cancer and the potential risk factors were evaluated. RESULTS: 205 women with biopsy diagnosis of HG-VaIN were considered, with a mean follow up of 57 months (range 4-254 months). 12 cases of progression to vaginal squamocellular cancer were observed (5.8%), with a mean time interval from treatment to progression of 54.6 months (range 4-146 months). The rate of progression was significantly higher in women diagnosed with VaIN3 compared with VaIN2 (15.4% vs. 1.4%, p < 0.0001). Women with HG-VaIN and with previous hysterectomy showed a significantly higher rate of progression to invasive vaginal cancer compared to non-hysterectomised women (16.7% vs. 1.4%, p < 0.0001). A higher risk of progression for women with VaIN3 and for women with previous hysterectomy for cervical HPV-related disease was confirmed by multivariable logistic regression analysis. CONCLUSIONS: A higher rate of progression to vaginal cancer was reported in women diagnosed with VaIN3 on biopsy and in women with previous hysterectomy for HPV-related cervical disease. These patients should be considered at higher risk, thus a long lasting and accurate follow up is recommended.

Intra-epithelial and invasive cervical neoplasia during HIV infection.

Patients affected by human immunodeficiency virus (HIV) infection present an elevated risk of developing cancer. In the last 10 years, the relationship between human papilloma virus (HPV) infection and female cervical intra-epithelial neoplasia (CIN) has been established. Several studies have described an increased prevalence of both cervical HPV infection and CIN among HIV-positive women compared to HIV-negative ones. A high recurrence rate of CIN after standard treatment has been noted in HIV-infected women and the severity of these lesions seems to be inversely correlated to immune function. Taking into account these data, the Centers for Disease Control (CDC) since 1993 have included invasive cervical carcinoma among the AIDS-defining conditions. Once cervical cancer develops in HIV-positive women, the disease may be aggressive and less responsive to treatment. A primary means by which HIV infection may influence the pathogenesis of HPV-associated cervical pathology is by molecular interaction between HIV and HPV genes. Although these have not been well defined, an upregulation of HPV E6 and E7 genes expression by HIV proteins (such as tat) has been postulated by some authors. Cervical cytology appears to be adequate as a screening tool for the cervical intra-epithelial neoplasia in HIV-positive women, but the high recurrence rate and multifocality of this disease reinforces the need for careful evaluation and follow-up of the entire anogenital tract in these women. Probably in the next few years, cervical tumours will represent one of the most frequent complications of HIV infection, a part of progression through AIDS. This points to a need for greater interdisciplinary co-operation for a best disease definition and for the development of effective prevention measures.

Squamous intraepithelial cervical lesions in human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the relationship between human immunodeficiency virus (HIV) infection, CD4 serum level, cervical squamous intraepithelial lesions (SILs) and risk factors for human papillomavirus (HPV)-related dysplasia in HIV-positive women. STUDY DESIGN: All 51 eligible patients who were seen at the Colposcopic Outpatient Service, Aviano Cancer Center, Aviano, Italy, from July 1, 1993, to June 30, 1994, were studied for risk factors for HPV and HIV infection and had cervical cytologic smears, colposcopy with cervical biopsy and a serum CD4 count. RESULTS: Thirty of 51 patients (59%) had cytohistologically confirmed SIL. The prevalence of SIL was higher in HIV Centers for Disease Control stage IV disease than stages II and III (22/29 vs. 8/22 P < .05). There was no significant difference in the CD4 count between women with or without SIL (321 +/- 310 vs. 401 +/- 295/mm3 [mean +/- SD]). No relationship was found between CD4 count and severity of SIL (low grade SIL, 210 +/- 203/mm3; high grade SIL, 580 +/- 357/mm3). CONCLUSION: In our series there was no relationship between CD4 count and cervical SIL, suggesting that the expression of HPV-related dysplasia is a complex process in which risk factors for genital SIL play an important role, while the role of HIV must be defined again.

Squamous cell carcinoma in ovarian endometriosis. A case report.

A primitive squamous cell carcinoma of the ovary arose in ovarian endometriosis. The patient underwent a radical hysterectomy and radiotherapy. The other few similar reported cases had a poor prognosis. In our case the patient died 11 months after surgery.

Papanicolau smear chances to be diagnostic for cervical squamous intraepithelial lesions (SIL) with or without detectable HPV DNA at in situ hybridization analysis.

The Authors have correlated 39 cervical diagnostic biopsies for squamous intraepithelial lesions (SILs) with correspective Papanicolau smears (PS), with relation to the presence or the absence of HPV of oncogenic type (HPV-one) detected by in situ hybridization (ISH). Agreement between cytological and histological diagnosis was present in 14 of 16 cases with detectable HPV-one and only in 12 of 23 cases without detectable HPV-one at ISH. The importance of the HPV type in the SILs with relation to the diagnostic accuracy of Papanicolaou smears has been discussed.

Histological diagnosis of human papillomavirus (HPV)-related dysplasia: quality control by in situ hybridization (ISH) analysis.

The Authors studied 54 cervical biopsies using in situ hybridization (ISH) to identify HPV related lesions. 26 biopsies lacked clear cut koilocytotic atypia on histological examination and 28 had a diagnosis of grades 1 and 2 intraepithelial neoplasia. Histological diagnosis of HPV-related dysplasia were studied using ISH with biotinylated probes (Phatogene DNA probe assay Enzo Diagnostics). Probes included HPV types 6/11, 16/18 and 31/35/51. HPV DNA were detected in 18 of 28 (64.3%) cervical biopsies with diagnosis of grade 1 and grade 2 cervical intraepithelial neoplasia with koilocytotic atypia. None of the 26 cervical biopsies equivocal for koilocytotic atypia had detectable HPV DNA with ISH. These results suggest that ISH can be used for the quality control in the histological diagnosis of koilocytotic atypia.

CA-125 serum level in the diagnosis of pelvic masses: comparison with other methods.

The Authors have evaluated the diagnostic contribution offered by the serum dosage of the antigen CA-125 in the diagnostics of pelvic masses. This method has been compared with the objective and echographic evaluation, as a noninvasive method of enquiry in the diagnosis of malignant neoplasias of the ovary. The Authors endorse the increase in diagnostic sensitivity brought about by the evaluation of this marker, above all if it is inserted into an integrated diagnosis.

[Antineoplastic agents and pregnancy]. / Antineoplastici e gravidanza.

The current impossibility of establishing a definite causal relationship between the administration of antineoplastic drugs before and/or during pregnancy and possible modifications of the gestational attitude in the treated women is discussed after a review of the Literature. The data till now reported are often deficient as far as concerns the evaluation of either the fetal, perinatal and post-natal parameters and the past and current reproductive performance of the patients on study. The need for strict methodology in the study and report of feto-maternal parameters to provide a comprehensive answer to the questions raised by the use of antineoplastic drugs before and/or during pregnancy is discussed in detail.

[True knots in the umbilical cord: clinical implications]. / Il nodo vero di funicolo: implicazioni cliniche.

A study was performed to study the behavior of various parameters of fetoplacental functions and fetal and neonatal well-being in 51 cases with the presence of true knots in the umbilical cord at birth. No statistically significant difference was observed when these cases were compared to a control group without this pathology. The Authors underline the need for precise statistical evaluations in order to reassess the clinical significance of such umbilical alterations.

[Local anesthesia in cervix biopsy]. / L'anestesia topica nelle biopsie della portio.

The Authors evaluated the perception of pain in a group of 35 patients undergoing cervical biopsy and the efficacy of using 40 mg of lydocaine (xylocaina spray) in 24 patients compared to a control group. Pain perception was evaluated using Scott-Huskissons's visual analogous scale. It was observed that this diagnostic method was painful and that premedication using topical anesthesia was an efficacious method of significantly reducing painful symptoms.

[Laser conization guided by endocervical staining with methylene blue]. / Conizzazione laser guidata mediante colorazione endocervicale con blu di metilene.

The authors report their experience of the use of a vital stain--methylene blue--as a surgical guide in laser cervical conization for CIN2-CIN3/CIS. During the period 1 October 1991-31 December 1992 a total of 40 laser cervical conizations were performed under local anesthesia using a CO2 laser connected to a microhandpiece and colposcope in patients with exo-endocervical lesions which were histologically positive for CIN2-CIN3/CIS. In 33/40 patients an aqueous solution of 1% methylene blue was introduced preoperatively in the endocervix using a cotton-wool bud with consequent impregnation of the pseudoglandular crypts: laser biopsy was performed along the guidelines of the stain itself. This enabled the direction of resection to be varied: in 3 patients due to an anomalous and eccentric direction of cervical canal; in 10 patients to remove glandular structures surrounding or underneath lesions; in 8 patients following pseudoglandular section to carry out deep vaporization (3 patients) or correct cutting edges (5 patients). The apex and edges of the cone were always intact. Fourteen patients completed a 12-month follow-up and a further 6 were followed up for 9 months; only 1/14 patients (with AIDS) showed recidivation after 1 year. In the authors' experience the use of a vital stain as a guide during laser cervical cone biopsy is an easily used method which ensures the greatest possible respect for healthy cervical structures, also in order to preserve fertility in young patients.

[Laser surgery in the conservative management of vaginal intraepithelial neoplasms]. / La laser chirurgia nel trattamento conservativo della neoplasia intraepiteliale vaginale (VaIN).

BACKGROUND AND AIMS: The increase finding of vaginal intraepithelial neoplasia (VaIN) in young women has led to the need to develop personalized conservative treatment. The authors studied the use of CO2 laser in the treatment of VaIN, evaluating the efficacy, repeatability, complications and the conservation of sexual function. METHODS: A total of 37 consecutive patients with histologically demonstrated VaIN (10 VaIN 1, 14 VaIN 2 and 13 VaIN 3): mean age 45.3 years, 37.8% aged < 35 years, 20/37 in childbearing age; VaIN was isolated in two patients, synchronous in 22 and in 13 cases it was metachronous with other intraepithelial or invasive genital neoplasia. 30/37 patients were treated with laser surgery as outpatients for a total of 41 operations (37 vaporisations and four excisions) using colposcopic guided CO2 laser with a constant emission power of 35 watts or 30 watts in the pulsed mode, under local anaesthesia, following the application of 5% acetic acid. RESULTS: Twenty-one (87.5%) of the 24 patients evaluated at 12 months were negative after one (16 patients) or more treatments (from 2 to 5 in 5 patients). Following the second recidivation, one elderly patient preferred traditional demolitive surgery; 2 patients are still awaiting further laser surgery. Five patients with multifocal lesions associated topical treatment with 5-fluorouracil. None of the sexually active patients complained of dyspareunias after treatment. CONCLUSIONS: Given the lack of other equally effective treatment and with the aim of preserving genital integrity, the authors regard laser surgery as the elective treatment for VaIN 2 and 3.

[Reliability of cytodiagnosis from washings and free fluid in the staging and follow-up of ovarian tumors]. / Affidabilità della citodiagnostica su washings e free fluid nella stadiazione e nel follow-up dei tumori ovarici.

181 diagnostic correlations between endocelomatic free-fluid or washing cytology and histological findings during staging or follow-up of patients suffering from ovarian cancer have been assessed. On the basis of the evaluation of the sensitivity and specificity of endocelomatic cytology, its importance in diagnostic protocols for evaluating the presence or persistence of disease is reiterated.