Prognosis of Human Papillomavirus-Negative Compared to Human Papillomavirus-Positive Cervical Cancer.

OBJECTIVES: The aims of the study were to evaluate the prevalence and prognosis of human papillomavirus (HPV)-negative cervical cancer (CC) and to compare these to data for HPV-positive CC. MATERIALS AND METHODS: This retrospective cohort study compared between HPV-negative CC and HPV-positive CC patients. Primary end points were disease-free survival and overall survival. Secondary end points were demographic and clinical variables including histological diagnosis, stage, and treatment. RESULTS: Of 233 women with CC, 18 (8%) tested HPV-negative. During a median follow-up of 45 months, 33 (14%) recurrences and 41 (18%) deaths were observed. Eleven of the 18 women (61%) who tested HPV-negative and 41 of the 215 (19%) who tested HPV-positive had only adenocarcinoma (p < .001). In a multivariate logistic regression analysis, advanced age (p = .003) and primary treatment with chemotherapy and/or radiotherapy (p < .001) remained statistically significant for recurrence or mortality (disease-free survival). The factors associated with lower survival were advanced age (p = .008), higher stage at diagnosis (p < .001), and HPV negativity (p = .062). Median overall survival for HPV-positive CC was not reached, compared with 24 months for HPV-negative CC. Kaplan-Meier curves showed lower rates of disease-free survival (p = .008) and overall survival (p = .011), for women with HPV-negative compared with HPV-positive CC. CONCLUSIONS: The relatively poor prognosis of HPV-negative CC is important in light of its relatively high prevalence, which could increase proportionally to HPV-positive CC due to increased HPV screening and vaccination. Further studies are needed to confirm whether HPV status is truly an independent prognostic factor in CC.

The Association Between Clearance of Human Papillomavirus After Conization for Cervical Cancer and Absence of Cancer.

OBJECTIVES: We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS: Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS: The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS: Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

The added benefit of transvaginal sonography in the clinical staging of cervical carcinoma.

INTRODUCTION: Patients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high-detail TVS, and positron emission tomography with 18 F-labeled fluoro-2-deoxyglucose and computed tomography (18 F-FDG PET/CT) may contribute to triage efficiency of cervical cancer patients. MATERIAL AND METHODS: This is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010-2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities-a thorough physical examination, a high-detail TVS, and positron emission tomography (PET) with 18 F-FDG and computed tomography (18 F-FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation. RESULTS: Seventy-three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone. CONCLUSIONS: The combination of high-detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18 F-FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.

Low-Risk Human Papillomavirus Types in Cervical Intraepithelial Neoplasia 2-3 and in Invasive Cervical Cancer Patients.

OBJECTIVES: A total of 95% to 99% of patients with invasive cervical cancer (CC) are infected with human papillomavirus (HPV). The aim of the study was to evaluate the incidence of low-risk HPV (LR-HPV) types among women with cervical intraepithelial neoplasia (CIN 2-3) and CC. MATERIALS AND METHODS: We conducted a nested cohort study of patients diagnosed with CIN 2-3 or CC. Inclusion criteria were diagnosis of CIN 2-3 or CC and HPV-DNA testing from the cervix. RESULTS: During the study period, we collected clinical data on 608 women of whom 402 were with CIN 2-3 and 206 with diagnosis of CC. When examining 14 high-risk HPV (HR-HPV) types, patients with CIN 2-3, 90.3% were found positive to at least one type of HR-HPV, 89.8% from CC patients were found positive to at least one type of HR-HPV. A total of 4.5% of patients with CIN 2-3 and 3.9% of those with CC were positive to only one LR-HPV or to some of a few LR-HPV types. Among 5.2% with CIN 2-3 and 6.3% of those with CC, no HPV types were detected. CONCLUSIONS: The prevalence of the LR-HPV in high-grade squamous intraepithelial lesion cervical lesions is low but is expected to increase in the future because of the expected decrease in CC caused by HPV types that are included in the bi-, quadri-, and nanovalent vaccine. The CIN 2-3 and CC patients with LR-HPV types and with negative HPV, challenge HPV screening sensitivity, which is based on a limited number of HR-HPV types.

Age-adjusted treatment of cervical intraepithelial 1 lesions by superficial or regular loop excision of transformation zone.

BACKGROUND: The loop electrosurgical excision procedure (LEEP) is one of the treatments for cervical intraepithelial neoplasia 1 (CIN1). One of the risks of LEEP is preterm birth. We evaluated final pathological diagnoses following LEEP as treatment for CIN1 lesions, for procedures in which cone height was determined by patients' age. METHODS: A retrospective study of 329 women diagnosed with CIN1 on a cervical biopsy and treated by LEEP. In patients under age 35 years, a thin LEEP COIN was performed, and in women over 35 years, a regular LEEP was performed. RESULTS: The final pathological diagnosis was CIN2 and CIN3 in 14.6% of the women. The average excision height was 0.64 cm in women aged under 35 years, 0.82 cm in women aged 36-45 years, and 0.96 cm in women older than 46 (P<0.0001). Comparing excision height less than 0.8 cm to excision height above 0.9 cm, complications of the procedure, positive margins rates and recurrence rates were similar. CONCLUSIONS: Among women of childbearing age, the performance of a LEEP procedure with smaller cone height appeared equivocal in achieving correct pathological diagnoses and low recurrence. To avoid increasing the risk of premature delivery, the excisional depth should be adjusted to age and fertility status.

The analgesic efficacy of forced coughing during cervical punch biopsy: A prospective randomised controlled study.

INTRODUCTION: Cervical punch biopsies are a common ambulatory procedure, performed routinely by gynaecologists. The aim of the present study was to assess the efficacy of forced coughing as a pain-reducing technique during cervical punch biopsy compared to a control group. MATERIALS AND METHODS: The study was a prospective randomised-control trial. The study group comprised 90 women who underwent cervical punch biopsies during investigation of abnormal Pap test results. The women were randomly assigned to 'cough' and control groups. Pain was measured on a 10 cm visual analogue scale (VAS) during different stages of the procedure. RESULTS: VAS pain score during biopsies was significantly lower in the 'cough' group. The median pain level in the 'cough' group was 1.5, compared to 4.0 in the control group. Eighty percent of the women in the 'cough' group reported a pain level of 2.0 or less compared to 40% of the women in the 'control' group (P = 0.0002). In the second biopsy, 69% of the women reported VAS ≤ 2.0 in the cough group compared to 28% of the patients in the control group. Forced coughing was shown both to reduce anxiety regarding the prospect of future cervical procedures and to decrease patients' desires for future pain management. This was true for 32% of the women in the 'control' group compared to 12% of the women in the 'cough' group (P = 0.05). CONCLUSION: Forced coughing provides significant pain relief during cervical punch biopsy and reduces the patients' fears and desires for pain medications in future procedures.

Prevalence and Genotype Distribution of HPV Types in Women at Risk for Cervical Neoplasia in Israel.

BACKGROUND: Invasive cervical cancer is caused by human papillomavirus (HPV). OBJECTIVES: To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia. METHODS: Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006-2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR). RESULTS: Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively. CONCLUSIONS: This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

Positive Correlation Between Clearance of High-Risk Human Papillomavirus and Lack of Residual Disease After Loop Excision of the Transformation Zone in Early Stage Cervical Cancer.

OBJECTIVES: In cervical cancer, a number of pathological parameters have been explored for their utility in tailoring a less aggressive approach for patients with low-risk early stage disease. We examined whether, in patients with cervical cancer stage IA1 to IB1, diagnosed by loop excision of the transformation zone (LLETZ), positive for high-risk human papillomavirus (hrHPV), clearance of hrHPV after LLETZ correlates with absence of residual disease at the final pathology after definitive or further surgery. MATERIALS AND METHODS: Data were collected from patients diagnosed with early stage invasive cervical cancer and positive hrHPV DNA, who had a repeat cervical HPV test 3 to 12 weeks after LLETZ and before final surgical treatment. We compared characteristics of patients with post-LLETZ negative and positive hrHPV. RESULTS: Of 28 patients, 13 were post-LLETZ negative hrHPV; of these, 11 did not have residual cancer in the final pathological specimen; two patients had cervical intraepithelial neoplasia 3. Of the 15 women who had post-LLETZ positive hrHPV, 10 had residual cancer in the final pathological specimen and 3 had cervical intraepithelial neoplasia or adenocarcinoma in situ; only 2 were negative for cancer. The post-LLETZ hrHPV test shows a sensitivity of 86.7% and specificity of 84.6%. CONCLUSIONS: Clearance of hrHPV from the cervix after LLETZ was found to correlate with the absence of residual cancer in the final surgical specimen. Testing for hrHPV post-LLETZ might serve as a new parameter for risk assessment and tailoring of a less radical operation in women with early stage cervical cancer.

Should the Risk of Invasive Cancer in Pregnancy and the Safety of Loop Electrosurgical Excision Procedure During the First 15 Weeks Change Our Practice?

OBJECTIVE: The aim of this article was to describe the outcome of women diagnosed with cervical intraepithelial neoplasia (CIN) grades 2 or 3 in pregnancy either observed or treated by loop electrosurgical excision procedure (LEEP) in the first 15 weeks of gestation. METHODS: Loop electrosurgical excision procedure during the first 15 gestational weeks compared with observation of CIN2/3. This is a retrospective analysis of a nonrandomized study at tertiary, academic, and referring centers in Israel. Ninety-three pregnant women diagnosed with CIN2/3 between 2006 and 2016 were included in this study. Fifty patients with CIN2/3 on cervical biopsy were conservatively followed-up, and 43 patients have undergone LEEP during the first 15 gestational weeks. Main outcome measures were ultimate diagnosis of invasive cancer or CIN, pregnancy outcome, and complications. RESULTS: In 5.4% of CIN2/3 during pregnancy, the final diagnosis was invasive cancer. The postpartum results of 50 women who were conservatively observed were as follows: 3 (6.0%) had cervical cancer and undergone radical hysterectomy, 33 (66.6%) had CIN2/3, and 14 (28%) had CIN1 or normal histology. The diagnoses of the 43 patients who have undergone LEEP were invasive cancer in 2 patients (4.6%) but did not undergo hysterectomy, CIN2/3 or adenocarcinoma in situ (AIS) in 38 patients (88.4%), and 3 women (7%) had CIN1 or normal histology. None of them suffered severe bleeding. Thirty-seven women continued their pregnancy, 34 (91.9%) had term deliveries, 2 (5.4%) gave birth at 34 and 36 weeks, and 1 patient had missed abortion (2.7%). CONCLUSIONS: The LEEP procedure during the first 15 weeks of pregnancy is safe. A total of 5.4% of the women with CIN2/3 during pregnancy were diagnosed with invasive cancer. It is time to reconsider the recommendations about CIN2/3 in early gestation.

High Incidence of Carcinosarcoma among Patients Previously Treated with Tamoxifen.

BACKGROUND: Tamoxifen acts as an estrogen antagonist within the breast tissue. In the uterus, tamoxifen is an agonist for some estrogen receptors and therefore can cause hyperplasia or neoplasia in the endometrium. OBJECTIVES: To compare characteristics of patients with uterine sarcoma who were and were not previously treated with tamoxifen. METHODS: The medical records of all women with uterine sarcoma who had been treated at the Carmel Medical Center in Haifa, Israel, during 2000-2013 were retrospectively reviewed. Disease characteristics, histological type of sarcoma, patient demographics, treatments and final outcomes were compared between patients who had and those who had not been exposed to tamoxifen. RESULTS: Of the 66 patients identified, 14 (21%) had been exposed to tamoxifen, one of them for 3 years and 13 for at least 5 years. Mean ages were 69 ± 8 and 66 ± 12 years for those exposed and those not exposed to the drug, respectively. Rates of uterine carcinosarcoma were 86% (12/14) and 44% (23/52), respectively (P < 0.006). Patients with carcinosarcoma were older than other sarcoma patients (73 ± 7 vs. 59 ± 11 P < 0.005).There were no statistically significant differences between the two groups in rates of diabetes mellitus, hypertension, dyslipidemia or heart disease. The mean time from diagnosis to death was 7.37 ± 0.42 years. The overall survival rates of carcinosarcoma patients were not statistically different from that of other sarcoma patients. Tamoxifen exposure was not associated with overall survival among all sarcoma patients, nor among the subgroup of carcinosarcoma patients. CONCLUSIONS: Tamoxifen treatment was associated with elevated incidence of carcinosarcoma among women with uterine sarcoma, but was not found to be associated with prognosis or with co-morbidities.

The prevalence of HPV types in women with CIN 2-3 or cervical cancer in Haifa district, Israel.

BACKGROUND: Human papilloma virus (HPV) is classified as a biologic carcinogen causing cervical cancer. Our aim was to identify all the HPV types responsible for cervical cancer and pre-cervical cancer in Israel. METHODS: This study included 226 women, diagnosed with cervical intraepithelial neoplasia (CIN) 2-3 and 115 women diagnosed with cervical cancer, and tested for all HPV typing during the period of January 2006 to May 2013. RESULTS: HPV was detected in 92.9% of women with CIN 2-3 and high-risk HPV (HR-HPV) was detected in 85.8% of them. In women with cervical cancer, HPV was positive in 96.5%, HR-HPV detected in 93%. In the CIN 2-3 group the most common HPV types were 16 (42%), 31 (8.8%) and 18 (4.9%) and in the cancer group HPV 16 (57.4%), 45 (9.6%), and 18 (7.8%). Multiple HPV types were seen in 12.8% of CIN 2-3 group but only in 0.9% of cancer group. The chief complaint led to cancer diagnosis was post menopause bleeding (27%), while abnormal Papanicolaou (Pap) test lead to CIN 2-3 diagnosis in 75.2% of the women. Only 22.6% of women diagnosed with cancer were diagnosed due to abnormal Pap test and 76.9% of them were diagnosed at stage I, as compared to women diagnosed with cancer because of bleeding or abnormal mass, of them 57.1 % were diagnosed at stage I (P<0.07). CONCLUSIONS: HR-HPV types were found in 93% of cancer group and 85.8% of CIN 2-3 group, and low-risk HPV (LR-HPV) was detected in 3.5% and 7.1% of women with cervical cancer and CIN 2-3 respectively. The most common HPV types in cervical cancer women were 16, 45 and 18. Women diagnosed with cancer because abnormal Pap test were in earlier stage compared to women diagnosed because of complains. Including LR-HPV types in screening HPV can increase the sensitivity of the test.

Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.

BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced. OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3). METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs. CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Cervical intraepithelial neoplasia 2, 3 in pregnancy: time to consider loop cone excision in the first trimester of pregnancy?

OBJECTIVES: To report the outcome of patients diagnosed with cervical intraepithelial neoplasia 2, 3 (CIN 2, 3) during pregnancy, who were treated by large loop excision of the transformation zone (LLETZ) in the first trimester or were followed up conservatively and treated after delivery. METHODS: Patients diagnosed with CIN 2, 3 during pregnancy who were treated with LLETZ or were conservatively followed up were included. Complications of the LLETZ, pathologic results, and pregnancy outcome of both groups were examined after delivery. RESULTS: Thirty-one patients were included in the study. Eighteen were conservatively followed up and 13 underwent LLETZ during the first 14 weeks of pregnancy. Four patients (12.9%) in the study group were diagnosed with invasive cervical cancer. From women who underwent LLETZ, 9 patients continued their pregnancy, 7 of which had term normal deliveries and 2 had late preterm deliveries. No complications of severe bleeding or miscarriage were reported in any of the treated patients. CONCLUSIONS: Large loop excision of the transformation zone procedure in the first trimester of pregnancy is a safe procedure, with the advantage of treating definitively CIN 2, 3 lesions and preventing the devastating consequences of undiagnosed cervical cancer. We suggest that LLETZ should be performed more liberally in the first trimester of pregnancy.

Cervical cancer screening, human papillomavirus vaccination practices and current infrastructure in Israel.

The incidence rates for premalignant lesions in Jewish women in Israel are similar to those observed in Western countries, but the incidence of cervical cancer in Israel is low; this discrepancy is not yet clearly understood. Because of the low incidence of cervical cancer in Israel, it was decided to base cervical cancer prevention on opportunistic screening: every woman from the ages of 35-54 years can have a Pap test smear free of charge every 3 years. Over the last decade 12.2% of the women population had an annual Pap test. From 36 to 50% of women who attended the Clalit Health Maintenance Organization (HMO) and the Maccabi HMO, the two largest HMOs in Israel, did so. There were also discrepancies between women of different socio-economic status (SES): <10% in the lowest SES level were screened compared to almost 55% in the higher level. HPV vaccination was opportunistic but it will be introduced to the school-based vaccine program at age of 13 years old as of September 2013. The Israel Society of Obstetrics and Gynecology recommends continuing cytologic screening in vaccinated women as recommended for the general population. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

Loop electrosurgical excision procedures in Israel.

AIM: To summarize data for cervical loop electrosurgical excision procedures (LEEP) in Israel from 2001 to 2007 inclusive. METHODS: 16 colposcopy specialists in Israel completed yearly questionnaires that assessed their LEEP. RESULTS: Of the 2,681 LEEP reported, cervical intraepithelial neoplasia 2/3 (CIN 2/3) and CIN 1 were the main indications, with 63.2 and 20.5%, respectively. CIN 2/3 was detected in 111 (20.4%) of those for whom CIN 1 was the indication for LEEP. Of those diagnosed with CIN 2/3 following LEEP, 34.8% (426/1,225) were in the 18- to 34-year age range. The agreement between punch and LEEP biopsies was 80.15% and the κ value was 0.536 (moderate agreement). Complications included severe bleeding in 3.02% during the procedure(s) and 2.99% in the 3 weeks following LEEP. CONCLUSIONS: In one-fifth of the women for whom CIN 1 was the indication for LEEP, CIN 2/3 was the final diagnosis. More than one-third of the cases of CIN 2/3 and carcinoma were diagnosed in women under the age of 35, the age at which Pap screening is offered in Israel. Based on these findings, the Israeli Society of Cervical Pathology and Colposcopy prepared guidelines for the treatment of CIN.

[Human papillomavirus types in women with cervical cancer in Haifa District].

BACKGROUND: Human papillomavirus (HPV) is recognized as the absolute cause of cervical cancer and is found in 99% of the Lesions. HPV 16 and 18 are detected in 70% of the cases. Two vaccines against HPV 16 and 18 were approved for use in Israel in recent years. PURPOSE: To determine the prevalence of human papillomavirus (HPV) in women with invasive cervical cancer in the Haifa district, and to see if the vaccine is suitable for our population. METHODS: The study population included 65 women from the Haifa District who were diagnosed with invasive cervical cancer in the Cervix Clinic of Carmel Medical Center. Samples for HPV typing were obtained during the evaluation of those patients. DNA was extracted from brush samples and HPV genotype was determined by nested-PCR followed by sequencing. RESULTS: Out of 65 patients with cervical carcinoma, 64 were found positive for HPV. The main HPV types in our patients were HPV 16 in 53.8% of the patients, HPV 18 in 12.3% of the patients and HPV type 45 in 13.8% of the patients. HPV type 33 was found in 4.6% of the patients, and HPV types 31 and 66 in 3.1% of the patients. Each of HPV types 54, 56, 58 and 59 were found in one patient. The main complaint was postmenopausal bleeding or menometrorrhagia in 24 patients (36.9%), post coital bleeding in 18 patients (27.7%) and 14 patients (21.5%) were evaluated due to an abnormal cytological smear Squamous cell carcinoma was diagnosed in 83% of the patients and cervical adenocarcinoma in 15.1% of them. CONCLUSIONS: The prevalence of HPV types in Haifa district is similar to world prevalence of HPV's, where HPV 16 and 18 cause 66.1% of cervical cancer, while in our study HPV45 and HPV 66 were found in higher proportions of cases than reported worldwide. In our population the vaccine against HPV 16/18 can prevent almost 70% of cases of cervical cancer, but a multicenter study should be performed in order to obtain larger numbers.

[Large loop excision of the transformation zone in Israel--2001].

BACKGROUND: Large loop excision of the transformation zone (LLETZ) is regarded as the treatment of choice in cases of Cervical Intraepithelial Neoplasia (CIN). Since the method is easy to learn and the equipment is inexpensive, many gynecologists now perform it in the clinic. Concern has been raised regarding the use of this procedure with insufficient indication by physicians who have not been adequately trained in performing LLETZ. AIM: This article aims to verify whether the indications for LLETZ in Israel are similar to those accepted in the updated literature and to discuss the need for licensure to perform LLETZ. Licensure would limit the use of LLETZ only to professionals specifically trained to conduct this procedure. METHOD: A questionnaire was sent to gynecologists, heads of obstetrics and gynecology departments as well as managers of public and private hospitals, regarding LLETZ performed in 2001. Topics covered in the questionnaire included: the number of LLETZ procedures performed, the patient's age, pre- and post-operative histopathological diagnosis, complications, follow-up and recurrence rate. The physicians were asked to complete separate questionnaires for each of the clinics in which he or she worked. RESULTS: The completed questionnaires comprised of 625 LLETZ procedures in eight public and three private colposcopy clinics. The ages of the women ranged from 18 to 70 years old, with 49% in the 18 to 34 age range. Most women (416) who underwent the LLETZ procedure had CIN grades 2 or 3. However, 128 women with CIN 1 were also treated. Among this group, 50% were confirmed CIN 1 according to the surgical specimen but 43 women had normal epithelium, 20 (15.6%) had high grade CIN (2-3) and one had invasive cancer. The most common post-operative short and long-term complication was heavy bleeding. Involvement of the surgical specimen borders was found in one fifth of the cases. CONCLUSIONS: The finding that about half of the women who underwent LLETZ were below the age of 35 years is of particular significance since the health insurance agencies in Israel only cover a pap smear screening test for women between the ages 35-54, once every three years. Therefore, there is an indication to start screening from the age 18. Similar to other countries in the world, the main indication to perform LLETZ in Israel is CIN 2-3. However, performing LLETZ for CIN 1 in many cases, and administering general anesthesia in certain centers, calls for the introduction of licensure for performing LLETZ. Involvement of the margins of the specimen in the neoplastic process in one fifth of the patients was similar to that reported in the literature. The various centers in Israel have different approaches as to the required surveillance period for women following LLETZ. It is suggested that women with involvement of the surgical specimen margins by CIN should be under medical surveillance at colposcopy clinics for a period of at least eight years.

Vesicovaginal fistula resulting from loop electrosurgical excision in a woman with intraepithelial neoplasia of the cervix and vagina: a case report.

A 52-year-old woman had concomitant cervical intraepithelial neoplasia (CIN) grade 3 and vaginal intraepithelial neoplasia grade 3. On performing a loop electrosurgical excision procedure, a vesicovaginal fistula accidentally occurred. The vaginal intraepithelial neoplasia covering the anterior fornix could have been a contributing factor in the occurrence of the fistula.