Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland:New data from northern Ireland and a systematic review and meta-analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta-analysis pooling the prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta-analysis was used to calculate a pooled HR-HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20-64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI, 12.7-13.7) among women with normal cytology and increased with cytological grade. In meta-analysis the pooled HR-HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and 0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland study and meta-analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type-specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR-HPV types other than HPV 16 and 18. J. Med. Virol. 85:295-308, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Freehand core biopsy in breast cancer: an accurate predictor of tumour grade following neoadjuvant chemotherapy?

Core biopsy is an increasingly used technique in the pre-operative diagnosis of breast carcinoma, as it provides useful prognostic information with respect to tumour type and grade. Neoadjuvant chemotherapy is being used in the treatment of large and locally advanced breast cancers but little is known regarding the correlation between tumour histology on pre-treatment core biopsy and that in residual tumour following primary chemotherapy and surgery. This study aimed to evaluate the accuracy of core biopsy in predicting these features in patients treated with primary chemotherapy. One hundred and thirty-three patients with carcinoma of the breast diagnosed on clinical, radiological and cytological examination underwent core biopsy, followed by primary chemotherapy (with cyclophosphamide, vincristine, doxorubicin and prednisolone) and surgery. The false-negative rate for pre-treatment core biopsy was 14%, with 91% agreement between the grade demonstrated on core biopsy and that in the residual tumour following completion of chemotherapy. Tumour type in the residual post-chemotherapy tumour was predicted by core biopsy in 84%. This study suggests that pre-treatment core biopsy histology accurately predicts residual tumour histology following primary chemotherapy and surgery in patients with breast cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

The management of radial scars of the breast - does core biopsy help?

Purpose: To compare the effectiveness of fine needle aspiration cytology (FNAC) with core biopsy (CB) in the pre-operative diagnosis of radial scar (RS) of the breast.

Patients and methods: A retrospective analysis was made of all radial scars diagnosed on surgical histology over an 8-year period. Comparison was made between the results of different preoperative needle biopsy techniques and surgical histology findings.

Results: Forty of 47 patients with a preoperative radiological diagnosis of radial scar were included in this analysis. Thirty-eight patients had impalpable lesions diagnosed on mammography and two presented with a palpable lump. FNAC (n=17) was inadequate in 47% of patients, missed two co-existing carcinomas found in this group, and gave a false positive or suspicious result for malignancy in 4 patients. CB (n=23) suggested a RS in 15 patients, but only diagnosed 4 out of 7 co-existing carcinomas found in this group.

Conclusion: CB is more accurate than FNAC in the diagnosis of RS. However, these data demonstrate that CB may offer little to assist in the management of patients with RS. In summary, this paper advocates the use of CB in any lesion with a radiological suspicion of carcinoma and diagnostic excision of all lesions thought to be typical of RS on mammography.

Commissioned Research on HPV Frequency in Cervical Cancers and Premalignant lesions of the Cervix

This report documents an investigation of the frequency of human papillomavirus (HPV) genotypes across cervical disease states in Northern Ireland ranging from koilocytosis to cervical cancer. It builds upon earlier work by the Northern Ireland HPV Working Group which reported a HPV prevalence of 17.1% overall in women aged 20-65 years irrespective of pathology and 13.2% among women in the screening age group (20-60 years) with normal cytology (Anderson et al. 2012, Anderson et al. 2013).

The BTA stat test:A tumor marker for the detection of upper tract transitional cell carcinoma

Objectives. To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine.

Methods. A total of 81 patients participated, 27 with histopathologically confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria but no evidence of urologic disease. Voided specimens collected before surgery or treatment were tested with the BTA stat test and VUC. UWC was performed in specimens collected by a ureteral catheter.

Results. The BTA stat test was significantly more sensitive and specific than VUC or UWC. The overall sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and 33%. The positive predictive value for the BTA stat test was 79% and the negative predictive value was 91%, both the highest of the three tests.

Conclusions. The BTA stat test was superior to VUC and UWC in the detection of UTTCC. These results may support the adoption of a less aggressive follow-up policy when monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is negative and the BTA stat test is positive, upper tract investigations should be expedited and, if the bladder is in place, bladder biopsies performed. (C) 2001, Elsevier Science Inc.

Physiologic indicators of vitamin A status.

Physiologic indicators reflect the functional consequences of vitamin A deficiency and may be particularly useful for detecting early perturbations in vitamin A status. In conjunctival impression cytology (CIC), epithelial morphology and the presence or absence of mucin spots and goblet cells allow samples, obtained by applying filter paper to the temporal conjunctiva, to be characterized as normal or typical of vitamin A-deficient keratinizing metaplasia. The validity of CIC has been established with reference to other indicators of vitamin A status, and a prevalence of > or =20% abnormal results has been suggested as indicative of a public health problem. However, interpretation of specimens requires considerable training, and nonresponsiveness to supplementation is a frequent problem, which limits the utility of CIC as a method for evaluating the impact of intervention programs. Several simplified field protocols for dark adaptation have been developed, including one in which dark adaptation is assessed by the responsiveness of the pupil to light. Night blind subjects have consistently shown abnormal results on this test, and a significant response to placebo-controlled dosing has been demonstrated for children and pregnant women. Scores have correlated significantly with serum retinol and relative dose response. Pupillary dark adaptation testing is acceptable to most children as young as 2 y old. Limitations of this technique include a time course for recovery after dosing as long as 4-6 wk, a testing time of 20 min, and the need for 1-3 d of training. Given its low cost, noninvasive nature, and lack of the need to transport samples, pupillary dark adaptation offers advantages over other techniques for assessing a population's vitamin A status.

Validation of immunocytochemistry as a morphomolecular technique

Immunocytochemistry (ICC) is a long-established means for clinical laboratories to investigate material for which it is difficult to obtain tissue samples. Unlike immunohistochemistry (IHC), the cells do not retain surrounding tissue environment/architecture. This can be of benefit in that fixation is often immediate and rapid, protecting the cells. Although fixation is frequently observed as the main preanalytic variable of test quality, all cytology preanalytic factors should be identified and controlled. In addition, the validation of ICC should take the same rigorous approach that other molecular pathology techniques follow. A three-step validation protocol is offered here. The end result is a comprehensive, morphomolecular approach to ICC, with an emphasis on therapeutic ICC.