Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

Abstract Background Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Methods Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). Results 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. Conclusions To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted.

Awareness and knowledge of HPV, cervical cancer, and vaccines in young women after first delivery in São Paulo, Brazil - a cross-sectional study

Abstract Background The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination for the general population. The aim of this study was to assess the level of awareness and knowledge of human papillomavirus (HPV) infection, cervical cancer prevention, vaccines, and factors associated with HPV awareness among young women after birth of the first child. Methods This analysis is part of a cross-sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who gave birth in that maternity hospital were included. A questionnaire that included questions concerning knowledge of HPV, cervical cancer, and vaccines was applied. To estimate the association of HPV awareness with selected factors, prevalence ratios (PR) were estimated using a generalized linear model (GLM). Results Three hundred and one primiparous women were included; 37% of them reported that they "had ever heard about HPV", but only 19% and 7%, respectively, knew that HPV is a sexually transmitted infection (STI) and that it can cause cervical cancer. Seventy-four percent of interviewees mentioned the preventive character of vaccines and all participants affirmed that they would accept HPV vaccination after delivery. In the multivariate analysis, only increasing age (P for trend = 0.021) and previous STI (P < 0.001) were factors independently associated with HPV awareness ("had ever heard about HPV"). Conclusions This survey indicated that knowledge about the association between HPV and cervical cancer among primiparous young women is low. Therefore, these young low-income primiparous women could benefit greatly from educational interventions to encourage primary and secondary cervical cancer prevention programs.

Frequency of gynecologic follow-up and cervical cancer screening in the Swiss HIV cohort study

BACKGROUND: According to current recommendations, HIV-infected women should have at least 1 gynecologic examination per year. OBJECTIVES: To analyze factors associated with frequency of gynecologic follow-up and cervical cancer screening among HIV-infected women followed in the Swiss HIV Cohort Study (SHCS). METHODS: Half-yearly questionnaires between April 2001 and December 2004. At every follow-up visit, the women were asked if they had had a gynecologic examination and a cervical smear since their last visit. Longitudinal models were fitted with these variables as outcomes. RESULTS: A total of 2186 women were included in the analysis. Of the 1146 women with complete follow-up in the SHCS, 35.3% had a gynecologic examination in each time period, whereas 7.4% had never gone to a gynecologist. Factors associated with a poor gynecologic follow-up were older age, nonwhite ethnicity, less education, underweight, obesity, being sexually inactive, intravenous drug use, smoking, having a private infectious disease specialist as a care provider, HIV viral load <400 copies/mL, and no previous cervical dysplasia. No association was seen for living alone, CD4 cell count, and positive serology for syphilis. CONCLUSIONS: Gynecologic care among well-followed HIV-positive women is poor and needs to be improved.

[Follow-up after malignant tumours of the uterus (cancer of the uterine corpus / cervical cancer)]

Malignant uterine tumours can affect the corpus or the cervix. The endometrial carcinoma with its different histological subtypes counts for most of the malignomas of the uterine body. But the rare category of uterine sarcomas (carcinosarcomas, leiomyosarcomas as well as endometrial stromal sarcomas) also belongs to this group. Cervical cancer presents an own entitity, regarding both histology and therapeutic options. Endometrial cancer is the most common genital malignoma in Northern Europe and North America. Histologically, the endometrial cancer can be subdivided in two groups: type I is hormonal sensitive and well differentiated, type II represents an undifferenciated aggressive tumour with poor prognosis. In general, the patient is elderly. Due to the main symptom - abnormal vaginal bleeding - endometrial cancer is detected in an early stage in about 75% of all patients. First choice in therapy is stage related surgery. Follow-up schemes have not proved yet to improve survival, therefore clear guidelines are missing. National and international groups recommend regular follow-up visits to detect the early vaginal vault relapse which is curable. Cervical cancer is mainly a squamous cell carcinoma and oncogenic Human Papilloma Virus (HPV) associated. Surgery is only indicated up to stage IIA, advanced stages should be treated by radio-chemotherapy. Several studies have shown that follow-up visits can improve survival rates. Intention is the detection of the curable local relapse.

[Cervical cancer screening in Switzerland - current practice and future challenges]

At the beginning of the 20th Century, cervical cancer was the leading cause of death from cancer in women. A marked decline in cervical cancer has been observed since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test as a cytological screening method. Today, Pap smear screening is still the most widely used tool for cervical cancer prevention. Testing for human papillomavirus (HPV) in cervical specimens or a combination of Pap and HPV testing are also now available. In this article we compare current guidelines for cervical cancer screening in Switzerland with those in other European countries. In view of the opportunities offered by HPV testing and, since 2008, HPV vaccination, current guidelines for cervical cancer screening should be updated. Both the choice of screening tests and general organization of cervical cancer screening should be reviewed.

IMRT with ¹⁸FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer

BACKGROUND To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC). METHODS The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control. RESULTS The median number of irradiated LNs per patient was 3 (range: 1-6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis. CONCLUSION IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer.

Diagnosis of cardiac metastasis from cervical cancer in a 33-year-old patient using multimodal imaging studies: a case report and literature review.

We report a case of a 33-year-old woman with emergency admission due to dyspnoea and fever. History included squamous cell carcinoma of the cervix in complete remission. Contrast-enhanced computed tomography (CT) scanning of the chest, which was indicated to rule out pneumonia, revealed an infiltrative cardiac mass. Further assessment of the tumour by echocardiography and cardiac magnetic resonance imaging (MRI) showed transmural infiltration of the apical interventricular septum with a mass extending into the left and right ventricle cavities. The mass was highly suspicious for a cardiac metastasis. Cardiac metastases from cervical cancer are extremely rare. Recurrence of cervical carcinoma involving the heart should be considered even after a curative therapy approach. Non-invasive imaging plays a paramount role in investigating cardiac masses. Echocardiography, CT and MRI are complementary imaging modalities for complete work-up of intracardiac lesions.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

An Insight Into Cervical Cancer Screening and Treatment Capacity in Sub Saharan Africa.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia.

Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer.

PURPOSE Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy. MATERIAL AND METHODS Thirty-nine patients with cervical carcinoma FIGO stage IB2 - IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with (18)FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15-18 Gy in three fractions (single fraction: 4-6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0). RESULTS Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness. CONCLUSION Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES To determine life expectancy for older women with breast cancer. DESIGN Prospective longitudinal study with 10 years of follow-up data. SETTING Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

Laparoscopic Indocyanine Green Sentinel Lymph Node Mapping in Pregnant Cervical Cancer Patients.

We present cases of 2 pregnant patients with early-stage cervical cancer who have undergone indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by laparoscopic SLN biopsy, pelvic lymphadenectomy, and cervical conization. Eight milliliters of ICG were injected in the 4 quadrants of the cervix after having obtained an adequate pneumoperitoneum and having inspected the abdominal cavity. SLNs were identified in both hemipelvises in both patients. In the final pathologic analysis, both SLNs and non-SLNs were negative for metastatic disease. No adverse events from ICG injection were recorded. ICG SLN mapping seems to be feasible in pregnant cervical cancer patients.

A Comparison of Radiocolloid and Indocyanine Green Fluorescence Imaging, Sentinel Lymph Node Mapping in Patients with Cervical Cancer Undergoing Laparoscopic Surgery.

BACKGROUND AND PURPOSE (99)TC combined with blue-dye mapping is considered the best sentinel lymph node (SLN) mapping technique in cervical cancer. Indocyanine green (ICG) with near infrared fluorescence imaging has been introduced as a new methodology for SLN mapping. The aim of this study was to compare these two techniques in the laparoscopic treatment of cervical cancer. METHODS Medical records of patients undergoing laparoscopic SLN mapping for cervical cancer with either (99)Tc and patent blue dye (Group 1) or ICG (Group 2) from April 2008 until August 2012 were reviewed. Sensitivity, specificity, and overall and bilateral detection rates were calculated and compared. RESULTS Fifty-eight patients were included in the study-36 patients in Group 1 and 22 patients in Group 2. Median tumor diameter was 25 and 29 mm, and mean SLN count was 2.1 and 3.7, for Groups 1 and 2, respectively. Mean non-SLN (NSLN) count was 39 for both groups. SLNs were ninefold more likely to be affected by metastatic disease compared with NSLNs (p < 0.005). Sensitivity and specificity were both 100 %. Overall detection rates were 83 and 95.5 % (p = nonsignificant), and bilateral detection rates were 61 and 95.5 % (p < 0.005), for Groups 1 and 2, respectively. In 75 % of cases, SLNs were located along the external or internal iliac nodal basins. CONCLUSIONS ICG SLN mapping in cervical cancer provides high overall and bilateral detection rates that compare favorably with the current standard of care.

Doppler Ultrasound Flow Evaluation of the Uterine Arteries Significantly Correlates with Tumor Size in Cervical Cancer Patients.

PURPOSE The aim of this present study was to evaluate the sonographic correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer, in order to establish a new potential marker to monitor treatment response. METHODS This was a retrospective cohort study of 25 patients who underwent a sonographic evaluation of Doppler flow characteristics of the uterine arteries before surgery or radiochemotherapy for early and locally advanced/advanced cervical cancer, respectively, was analyzed. The primary outcome was the correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer. RESULTS Median age was 49 (range 26-85) years, and mean tumor size was 40.8 ± 17 mm. A significant positive correlation was found between tumor diameter and the uterine artery end-diastolic velocity (r = 0.47, p < 0.05) as well as the peak systolic velocity (r = 0.41, p < 0.05). No correlation was found between tumor size and the pulsatility index or resistance index. CONCLUSIONS In cervical cancer, uterine artery velocity parameters are associated with tumor size. This finding could become particularly useful in the follow-up of locally advanced cervical cancer patients undergoing radiochemotherapy or in corroborating the selection of women with more possibility of a high response rate during neoadjuvant chemotherapy before surgery.