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.

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.

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.

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.

[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.