HPV testing in primary screening of older women

Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml−1 cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme. © 1999 Cancer Research Campaig

Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease

Background: Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise. Methods: This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed. Results: On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism. Conclusion: Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences

Adverse outcomes after colposcopy

Abstract Background Colposcopy is an essential part of the National Health Service Cervical Screening Programme (NHSCSP). It is used for both diagnosis and treatment of pre-cancerous cells of the cervix. Despite colposcopy being a commonly performed and relatively invasive procedure, very little research has explored the potential long-term impacts of colposcopic examination upon patient quality of life. The aim of this study is to investigate and quantify any potential reduction in women's quality of life following a colposcopy procedure. More specifically, the degree of female sexual dysfunction and the excess risk of adverse events in those undergoing colposcopy will be explored. If such risks are identified, these can be communicated to women before undergoing colposcopy. It will also assist in identifying whether there are particular sub-groups at greater risk and if so, this may lead to a re-evaluation of current recommendations concerning colposcopically directed treatments. Methods/design Cohort study using postal surveys to assess sexual function and quality of life in women who have attended for colposcopy (cases), compared with those who have not attended colposcopy (controls). The prevalence and excess risk of female sexual dysfunction will be determined. Logistic regression will identify the predictors of adverse outcomes. Discussion There are more than 400,000 colposcopy appointments each year in England, of which 134,000 are new referrals. There is some evidence that there may be long-term implications for women treated under colposcopy with respect to adverse obstetric outcomes, persisting anxiety, increased rates of sexual dysfunction and reduced quality of life. Reliably establishing whether such adverse outcomes exist and the excess risk of adverse events will facilitate informed decision-making and patient choice.</p

Type distribution, viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer (CIN)

A series of 176 archival cervical intraepithelial neoplasia (CIN) was analysed for the presence, viral load and integration status of ‘high-risk' types of human papillomavirus (HR-HPV). The samples were assayed using newly developed methods based on real-time PCR. Two methods for the extraction of DNA from the paraffin-embedded biopsies were compared: a protocol based on the MagNA pure system (Roche) and a Qiagen spin column kit (Qiagen). It was possible to amplify 94% (166) of the samples. Of these, 36, 63 and 80% of the CIN I, II and III cases contained HR-HPV. HPV 16 was the most prevalent, and was found in 20, 28 and 46% of the CIN I, II and III cases, respectively. The second most frequent HR-HPV was type 33 group, and in CIN II it was as prevalent as HPV 16. The median number of copies of HR-HPV per cell was not significantly different in the CIN I, II and III cases, but there was a wide range of viral load values over several magnitudes, regardless of the grade of CIN. All samples were found to contain integrated forms of HPV 16, frequently mixed with an episomal form

The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies