Evaluation of downstaging in the detection of cervical neoplasia in Kolkata,India

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30-64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia.     

Determinants of cervical cancer rates in developing countries

Although cervical cancer (CC) is a leading cause of cancer-related deaths in developing countries, incidence rates vary considerably, ranging from 3 to 61 per 10(5) females. Identifying determinants of high vs. low rates may suggest population-level prevention strategies. CC rates for 175 countries were obtained from the IARC. Country-specific behavioral, health, economic and demographic measures were obtained from United Nations agencies and other international organizations. Regression analyses performed for 127 low or medium developed countries identified both geography and religion as independently associated with high CC rates. Among behavioral measures, high fertility rates, early age at birth of first child and high teenage birth rates were significantly associated with high CC rates. Countries with high CC rates had fewer doctors per capita, less immunization coverage, more HIV infections and shorter life expectancies. CC rates also tended to be higher in countries with more spending on health and younger, less educated populations. Patterns of CC rates suggest that programmatic approaches, such as promoting delayed childbearing and sexual monogamy, may be appropriate interventions. For countries with high CC rates and some flexibility in their health-care budgets, a once-in-a-lifetime screen of women 30-50 years of age, using Pap smears, direct visual inspection and/or HPV DNA testing, may be cost-effective. Finally, relatively low immunization rates and a shortage of health-care workers in countries with high CC rates suggest potential challenges for introducing prophylactic HPV vaccines.     

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.     

Recurrent human papillomavirus infection detected with the hybrid capture II assay selects women with normal cervical smears at risk for developing high grade cervical lesions: a longitudinal study of 3,091 women

To test the reliability of the Hybrid Capture II (HC-II) assay detecting 13 high-risk human papillomavirus (HR-HPV) types for the screening of cervical lesions, we monitored by cytology, HR-HPV testing, colposcopy and biopsy, 3,091 women with normal smears at the first entry. Our primary endpoint was clinical progression defined as the presence of a high-grade lesion (HGSIL) at the biopsy. In our population of 659 HR-HPV-infected women, 241 (36.6%) had a positive HR-HPV test at 2 to 4 examinations with a final histological diagnosis of HGSIL in 51 cases (21.2%) within 4 to 36 months, while women with regressive HPV infection did not develop any lesion during the same period. In the cohort of 2,432 women testing negative for HR-HPV infection, only 2 women (0.08%) developed a HGSIL. Both were HR-HPV positive 18 and 24 months after the first entry, at the time of diagnosis of disease. The RR of incident HGSIL when a HR-HPV was detected at enrollment in women with normal smears was 96.7 (95% CI, 95.8-97.7). The RR increased to 237.3 (95% CI, 222.8-251.8) when the HR-HPV test remained positive at 2 controls, and to 314.3 (95% CI, 260.7-367.9) when the HR-HPV test was positive at 3 controls. The evaluation of the viral load of HR-HPV by the HC-II did not represent a sensitive approach to predict the recurrence of HR-HPV infection and/or the apparition of HGSIL. Nevertheless, a recurrent HR-HPV infection detected with HC-II represents a reliable tool to select populations at risk for the development of HGSIL.     

A proposal for cervical screening information systems in developing countries

The effective and efficient delivery of cervical screening programs requires information for planning, management, delivery and evaluation. Specially designed systems are generally required to meet these needs. In many developing countries, lack of information systems constitutes an important barrier to development of comprehensive screening programs and the effective control of cervical cancer. Our report outlines a framework for creating such systems in developing countries and describes a conceptual model for a cervical screening information system. The proposed system is modular, recognizing that there will be considerable between-region heterogeneity in current status and priorities. The proposed system is centered on modules that would allow for the assembly and computerization of data on Pap tests, since these represent the main screening modality at the present time. Additional modules would process data and create and maintain a screening database (e.g., standardize, edit, link and update modules) and allow for the integration of other types of data, such as cervical histopathology results. An open systems development model is proposed, since it is most compatible with the goals of local stakeholder involvement and capacity-building.     

Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells

Lipoxygenase metabolites of arachidonic acid can act as growth promoting factors for various cancer cell lines. Here we demonstrate that the 5-lipoxygenase inhibitor nordihydroguaiaretic acid potently inhibits anchorage-independent growth of human pancreatic and cervical cancer cells in soft agar and delays growth of pancreatic and cervical tumours established in athymic mice. Furthermore, nordihydroguaiaretic acid induces apoptosis of these cancer cells in vitro and in vivo. Potential mechanisms mediating these effects of nordihydroguaiaretic acid were examined. Nordihydroguaiaretic acid had no inhibitory effect on growth and survival signals such as tyrosine phosphorylation of the epidermal growth factor receptor or basal and growth factor-stimulated activities of extracellular signal-regulated kinase 1/2, p70(s6k) and AKT but selectively inhibited expression of cyclin D1 in the cancer cells. In addition, treatment with nordihydroguaiaretic acid lead to a disruption of the filamentous actin cytoskeleton in human pancreatic and cervical cancer cells which was accompanied by the activation of Jun-NH(2)-terminal kinase and p38(mapk). Similar effects were obtained by treatment of the cancer cells with cytochalasin D. These results suggest that nordihydroguaiaretic acid induces anoikis-like apoptosis as a result of disruption of the actin cytoskeleton in association with the activation of stress activated protein kinases. In conclusion, nordihydroguaiaretic acid could constitute a lead compound in the development of novel therapeutic agents for various types of cancer.     

Postoperative low-pelvic irradiation for stage I-IIA cervical cancer patients with risk factors other than pelvic lymph node metastasis

: To retrospectively investigate whether postoperative low-pelvic radiotherapy (RT) is an appropriate treatment for node-negative, high-risk Stage I–IIA cervical cancer patients.

: A total of 228 Stage I–IIA cervical cancer patients treated by radical surgery and postoperative RT were included in this study. All patients had histopathologically negative pelvic node metastasis, but at least one of the following risk factors: parametrial involvement, positive or close resection margins, invasion depth two-thirds or greater cervical stromal thickness. Seventy-nine patients (35%) received 30–50 Gy (median 44) to whole pelvis and a boost dose to the low pelvis (whole-pelvic RT group); the other 149 patients (65%) received low-pelvic RT only (low-pelvic RT group). For both groups, the total external RT dose to the low pelvis ranged from 40 to 60 Gy (median 50). The potential factors associated with survival, small bowel (gastrointestinal) complications, and leg lymphedema were analyzed, and patients who had a relapse in the upper pelvis were identified.

: The 5-year overall and disease-specific survival rate was 84% and 86%, respectively. After multivariate analysis, only bulky tumor (≥4 cm) and non-squamous cell carcinoma were significantly associated with survival. Parametrial involvement, lymph-vascular invasion, ≤50.4 Gy to the low pelvis, positive or close margins, and low-pelvic RT alone did not significantly affect survival. Grade I–V small bowel complications occurred in 33 patients (15%). Whole pelvic RT and >50.4 Gy to the low pelvis, but not old age and treatment technique (AP-PA vs. box), were significantly associated with gastrointestinal complications. Three patients (2%) in the low-pelvic RT group and 6 patients (8%) in the whole-pelvic RT group were found to have Grade III or higher small bowel complications (p = 0.023). Thirty-one percent of patients developed lymphedema of the leg. A dose to the low pelvis >50.4 Gy and an AP-PA field, but not whole-pelvic RT, old age, or the number of sampled lymph nodes, were associated with lymphedema of the leg. Five patients (3.6%) of the low-pelvic RT group and none of the whole-pelvic RT group developed upper pelvis relapse. Three of these 5 patients had upper pelvic relapse alone.

: Compared with whole-pelvic RT plus low-pelvic boost, low-pelvic RT alone significantly reduces the small bowel complications in node-negative, high-risk, Stage I–IIA cervical cancer patients. Although low-pelvic RT alone increases the incidence of upper pelvic relapse, its effect on survival is not substantial. Low-pelvic RT alone appears to be an appropriate treatment method for this group of patients.     

Hepatic pseudocyst as the first presentation of squamous cell carcinoma of uterine cervix

We describe a patient with diffuse polycystic disease of the liver. The patient's polycystic liver disease was found to be due to liver metastases from squamous cell carcinoma of the uterine cervix. No evidence of discrete masses was found in the liver using abdominal CT scan. Pseudocystic formation in the liver secondary to squamous cell carcinoma is very rare and has not previously been reported as a first presentation of a cervical cancer. Metastatic neoplasms need to be considered in the differential diagnosis of hepatic cysts.     

Carcinoma in situ in a lateral cervical cyst

BACKGROUND: The development of an invasive squamous cell carcinoma within a lateral cervical cyst as a result of malignant transformation of the epithelium is considered a rare circumstance. The existence of this entity is a source of controversy in light of the differential diagnosis, which includes a cervical metastasis from an unknown primary carcinoma (CUP-syndrome). Apart from site, histologic findings, and follow-up, the principal diagnostic criterion for lateral cervical cyst carcinoma is the histomorphologic demonstration of transition of the benign epithelium into invasive squamous cell carcinoma. Although numerous case reports of this entity exist, carcinoma in situ in a lateral cervical cyst has been reported in only five cases thus far. METHOD: In this context, we present the case of a 44-year-old patient with a 7-month history of cervical swelling. RESULTS: After diagnostic extirpation of the tumor, histologic findings were consistent with a lateral branchial cyst with high-grade dysplasia and carcinoma in situ of the squamous epithelial lining. CONCLUSION: This case of a premalignant lesion within a lateral branchial cyst (ie, carcinoma in situ) supplies the "missing link" and adds credibility to the concept of primary branchiogenic carcinoma.