Comparison of the AMPLICOR human papillomavirus test and the hybrid capture 2 assay for detection of high-risk human papillomavirus in women with abnormal PAP smear.

Infection with human papillomavirus (HPV) is a necessary step in the progression to cervical cancer. Many methods for HPV testing are currently available, mostly developed to detect pools of HPV types. Hybrid Capture 2 (HC2) is one of the most widely used. A new PCR-based assay, the Roche AMPLICOR HPV test, has been recently developed. Both assays recognize a group of 13 HR HPV types contemporaneously. This study evaluated the performance of both methods for detecting high-grade cervical lesions as a part of management for abnormal PAP smears. The study population was composed of 213 women, all referred to colposcopy and histologic diagnosis following an abnormal PAP test. Biopsy-confirmed high-grade cervical intraepithelial neoplasia was used as a gold standard. Overall agreement was 84.9% with a kappa value of 0.6. When comparing the ability to detect moderate cervical intraepithelial neoplasia (CIN2+) and high-grade cervical intraepithelial neoplasia (CIN3+/cancer), AMPLICOR proved slightly more sensitive than HC2, a finding that is important when HPV testing is used in a triage of borderline smear results. Genotyping of discordant results showed a prevalence of LR-HPV types in HC2 positive/AMPLICOR negative samples, and a similar prevalence of HR- and LR-HPV types in AMPLICOR positive/HC2 negative samples. In conclusion, the study shows that the AMPLICOR assay is more sensitive than HC2, which makes it a valid alternative for routine clinical use.

Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women.

The prevalence of single and multiple HPV infections was assessed over a cohort of 213 women with cytological abnormalities and its association with cervical neoplasia established. Roche linear array HPV genotyping test was used to identify HPV genotypes. The most prevalent HPV genotypes in cervical cancer samples were HPV16 (61.2%), HPV52 (16.1%), HPV18 (12.9%) and HPV 31 (9.6%). Multiple HR and LR HPV infections, comprising between two and 5+ HPV types, were identified in 49.7% of samples, with a significantly lower number in severe dysplasia and cervical cancer samples (p<0.05). These results seem to indicate that detection of multiple HPV infection with HR-HPV types is not significantly better as a predictor of cervical cancer than single HR-HPV infection, though further longitudinal studies are needed to better clarify the relevance of these infections to the progression of cervical neoplasia.

Detection and genotyping of human papillomavirus in cervical samples from Italian patients.

Human papillomaviruses (HPVs) are etiological agents of cervical cancer. In order to assess the epidemiological incidence and frequency of different HPV types, we applied a polymerase chain reaction (PCR)-direct sequencing approach based on the use of MY09/MY11 primers as compared to Hybrid Capture assay. Cervical samples were taken from 1,500 women, both with normal and abnormal cytological smears, and we found an incidence of 6.6% of HPV infection in Brescia. Overall, 97 samples tested HPV-positive, yielding 18 HPV types. The four most frequent HPV types were: HPV 16, -31, -6, and -58. This approach could be used in ordinary laboratory settings for quick and reliable typing of known and novel HPVs from clinical specimens and it could also be applied to anti-cancer vaccine development.

Biologic activity of tamoxifen at low doses in healthy women.

BACKGROUND: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use. METHODS: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/ alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. RESULTS: After adjustment for the baseline values, there were reductions in circulating levels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which showed a decrease, was the only parameter exhibiting change. CONCLUSIONS: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.

Adrenal androgen-secreting carcinoma in a fertile woman.

The article reports on a case of functioning adrenal carcinoma in a woman of 40 with concomitant in situ carcinoma of the portio (CIN 3). She had had amenorrhoea for 14 months and early menopause was suspected. Hirsutism and other signs of virilization such as clitoromegaly and voice changes were detected upon hospitalization.. The characteristic of the clinical case is given by hormone production involving not only androgens of prevalently adrenal genesis (dehydroepiandrosterone, dehydroepiandrosterone sulphate and androstenedione), but also testosterone, more suggestive of a gonadal neoplasm. The adrenal carcinoma only produced androgens, as plasma cortisol and aldosterone concentrations were normal. Diagnosis of adrenal carcinoma was first made with hormone assays and then with the adrenal block test using dexamethasone, with adrenal ecography and abdomino-pelvic computed tomography (CT). When amenorrhoea is present and hirsutism and other signs of virilization occur ex-novo in a short period, in a woman of fertile age, a thorough endocrine study must be carried out. According to the hormone profile, the next diagnostic step should be aimed at detecting a prospective ovarian or adrenal neoplasm.