High-risk human papillomavirus testing versus cytology in predicting post-treatment disease in women treated for high-grade cervical disease: a systematic review and meta-analysis.

OBJECTIVE: Currently, women treated for high-grade cervical intraepithelial neoplasia (CIN 2/3) are followed-up by cytology to monitor them for residual and recurrent (post-treatment) disease. This systematic review and meta-analysis determine the test performance of testing for high-risk types of the human papillomavirus (hrHPV), cytology and co-testing (combined hrHPV testing and cytology) in predicting high-grade post-treatment disease (CIN2+). METHODS: Studies that compared at least two of three post-treatment surveillance methods, and were published between January 2003 and May 2011, were identified through a bibliographic database search (PubMed, Embase.com and Wiley/Cochrane Library). Identification of relevant studies was conducted independently by two reviewers with a multi-step process. The reference standard used to diagnose post-treatment disease was histologically confirmed CIN2+. Sensitivity, specificity, diagnostic odds ratios and relative sensitivity and specificity were calculated for each study. Pooled estimates were calculated using a random effects model if heterogeneity among studies was significant, otherwise by using a fixed effects model. Estimates were reported with 95% confidence intervals (95%CI). RESULTS: Out of 2410 potentially relevant citations, 8 publications, incorporating 1513 treated women, were included. Pooled sensitivities were 0.79 (95%CI 0.72-0.85) for cytology, 0.92 (0.87-0.96) for hrHPV testing, and 0.95 (0.91-0.98) for co-testing. HrHPV testing was more sensitive than cytology to predict post-treatment CIN2+ (relative sensitivity 1.15; 95%CI 1.06-1.25). Pooled specificities were 0.81 (95%CI 0.74-0.86) for cytology, 0.76 (0.67-0.84) for hrHPV testing and 0.67 (0.60-0.74) for co-testing. HrHPV testing and cytology had a similar specificity (relative specificity 0.95, 95%CI 0.88-1.02). CONCLUSIONS: This review indicates that the hrHPV test should be included in post-treatment testing 6months after treatment, because hrHPV testing has a higher sensitivity than cytology in detecting high-grade post-treatment disease and has a similar specificity.

Offering self-sampling for human papillomavirus testing to non-attendees of the cervical screening programme: Characteristics of the responders.

BACKGROUND: Self-sampling for high-risk human papillomavirus (hrHPV) testing is accepted by up to 30% of non-attendees to the regular cervical screening programme. Here, the yield of cervical intraepithelial neoplasia (CIN)2 or worse (≥ CIN2) and CIN3 or worse (≥ CIN3) of 15, 274 HPV self-sampling responders amongst non-attendees were compared to that of 176, 027 women participating in regular screening in the same period and in the same region. We also analysed which subpopulations amongst non-attendees are targeted by HPV self-sampling, and which characteristics relate to hrHPV prevalence and yield of ≥ CIN2/≥ CIN3. METHOD: Data from two consecutive self-sampling studies were pooled. ≥ CIN2/≥ CIN3 yields, screening history, age and ethnic status were retrieved from centralised pathology and screening databases, respectively. A logistic regression model was fitted to analyse method of invitation, ethnicity, age group, and screening history as predictors for response rate, hrHPV presence and ≥ CIN2/≥ CIN3 in non-attendees. For screening history analyses, women < 34 years were excluded since it was the first screening round in their life. FINDINGS: ≥ CIN2/≥ CIN3 yields of HPV self-sampling responders were higher than those of screening participants (≥ CIN2: relative risk (RR) = 1.6, 95% confidence interval = 1.4-1.9; ≥ CIN3: RR = 1.8, 95%CI = 1.5-2.1 with relative risk values increasing with age (test of homogeneity:≥ CIN2: p = 0.04; ≥ CIN3: p=0.03). Native Dutch non-attendees responded better than immigrants (32% versus 22%, p<0.001) and those screened in the previous round revealed a higher response than underscreened (i.e. previous smear taken >7 years ago) or never screened (34% versus 25%, p<0.001) women. Strikingly, amongst under- and never screened women aged ≥ 39 years, never screened women responded better (25% versus 23%, p<0.001). ≥ CIN2 rates were higher amongst responding native Dutch women than immigrants (p<0.01), and higher in under-/never screened women than in women screened in the previous round (p<0.01). INTERPRETATION: Offering hrHPV self-sampling increases the efficacy of the screening programme by targeting a substantial portion of non-attendees of all ethnic groups who have not regularly been screened and are at highest risk of ≥ CIN2.

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer.

PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and etoposide when administered in combination to previously-untreated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited-stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients was similar (73 vs 74%, respectively), the percentage complete response was significantly higher among the former (49 vs 20%). The main toxicities were grade 3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were 3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and 39% in ESD patients, respectively. CONCLUSION: The results indicate that the combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity in SCLC that is comparable to other combination regimens, and is well tolerated.

Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial.

Fifty-six patients with measurable or evaluable advanced gastric cancer were treated with cisplatin, 100 mg/m2 in continuous infusion of 24 hours, and 5-fluorouracil, 1000 mg/m2/day (by continuous 5-day infusion) every 4 weeks. Three patients were found ineligible for the study. A response rate of 41% (22/53) was obtained (95% confidence interval: 28%-54%), with a median duration of remission of 10.2 months and an overall median survival time of 10.6 months. Leukopenia and thrombocytopenia were mild. Nausea and vomiting were common, and 23.5% of the patients had grade 3 stomatitis. Peripheral neuropathy and renal insufficiency increased with the number of cycles, representing the cumulative dose-limiting toxicity. This study indicates that the combination of cisplatin plus 5-fluorouracil is synergistic or at least has additive antitumor activity. We think that this association of 2 drugs should be considered for further phase III clinical trials.

[Intra-arterial chemotherapy, using the hepatic artery, in metastases of colorectal carcinoma]. / Quimioterapia intra-arterial hepática en las metástasis del carcinoma colorrectal.

Hepatic metastasis is the major cause of death in advanced cancer of the colon and rectum. Various modes of therapy have been attempted with only partial success. Infusion of cytotoxic agents into the hepatic artery has allowed a higher concentration of drug into the tumor capillary bed than is achievable with intravenous administration. We review the data on therapeutic outcome, administration techniques and toxicity of hepatic arterial chemotherapy for colorectal cancer metastatic to the liver.