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We present data on the use of the Hybrid Capture 2 (HC2) test for the detection of high-risk human papillomavirus (HR HPV) with different thresholds for positivity within a primary screening setting and as a method of triage for low-grade cytology. In the ARTISTIC population-based trial, 18,386 women were screened by cytology and for HPV. Cervical intraepithelial neoplasia lesions of grade two and higher (CIN2؉ lesions) were identified for 453 women within 30 months of an abnormal baseline sample. When a relative light unit/cutoff (RLU/Co) ratio of >1 was used as the threshold for considering an HC2 result positive, 15.6% of results were positive, and the proportion of CIN2؉ lesions in this group was 14.7%. The relative sensitivity for CIN2؉ lesion detection was 93.4%. When an RLU/Co ratio of >2 was used as the threshold, there was a 2.5% reduction in positivity, with an increase in the proportion of CIN2؉ lesions detected. The relative sensitivity decreased slightly, to 90.3%. Among women with low-grade cytology, HPV prevalences were 43.7% and 40.3% at RLU/Co ratios of >1 and >2, respectively. The proportions of CIN2؉ lesions detected were 17.3% and 18.0%, with relative sensitivities of 87.7% at an RLU/Co ratio of >1 and 84.2% at an RLU/Co ratio of >2. At an RLU/Co ratio of >1, 68.3% of HC2-positive results were confirmed by the Roche line blot assay, compared to 77.2% of those at an RLU/Co ratio of >2. Fewer HC2-positive results were confirmed for 35-to 64-year-olds (50.3% at an RLU/Co ratio of >1 and 63.2% at an RLU/Co ratio of >2) than for 20-to 34-year-olds (78.7% at an RLU/Co ratio of >1 and 83.7% at an RLU/Co ratio of >2). If the HC2 test is used for routine screening as an initial test or as a method of triage for low-grade cytology, we would suggest increasing the threshold for positivity from the RLU/Co ratio of >1, recommended by the manufacturer, to an RLU/Co ratio of >2, since this study has shown that a beneficial balance between relative sensitivity and the proportion of CIN2؉ lesions detected is achieved at this threshold.Persistent infection with any of the 15 cancer-associated high-risk human papillomavirus (HR HPV) genotypes is now well recognized as essential for the subsequent development of cervical cancer and its high-grade precursor lesions (2,15,16). Due to the very high prevalence of HPV infections that typically resolve within 1 to 2 years, especially in younger women (6, 11), the role of HPV testing in the early detection of cervical lesions remains controversial. The most widely used test for the detection of a group of 13 HR HPV genotypes is the commercially available, FDA-approved Hybrid Capture 2 high-risk HPV DNA test (HC2 test; Qiagen [formally known as Digene]). Hybrid Capture 2 technology consists of a nucleic acid hybridization assay with signal amplification that utilizes microplate chemiluminescence for the qualitative detection of HPV. There is increasing interest in the use of HC2 technology within the cervical screening program either as a stand-alone screening test or i...

Women with abnormal smears have an increased risk of developing cervical cancer. During the 8 years following conservative treatment of cervical intraepithelial neoplasia (CIN), their risk of invasive cervical cancer is about 5 times greater than that of the general population. Human papillomavirus (HPV) has been associated with the natural history of both CIN and cervical cancer. To date, there have been no published reports on the predictive value of HPV testing in the treatment outcome of CIN. A prospective, multi-center, cohort study was conducted on women in the Northwest of England who were attending for treatment of CIN. They were asked to complete a questionnaire, which included a detailed smoking history. Pre-and post-treatment HPV testing was performed on cervical biopsies and cervical swab, being taken with the first follow-up smear at 6 months. A nested case-control analysis was performed, cases being de- Carcinoma of the cervix is the leading cause of female cancer mortality in the developing world. 1 In developed countries, the implementation of cervical screening has had a significant impact on the incidence of cervical cancer because of the early detection of the pre-invasive disease and its effective treatment. During the 8 years following treatment of cervical intraepithelial neoplasia (CIN) the risk of invasive cervical cancer for these women remains about 5 times greater than that of the general population of women. 2 Treatment failure of CIN has been found to be associated with the size of the lesion, partially involved excision margins and the degree of CIN. 3-5 Current methods of treatment have all been associated with success rates of 90 -95%. 3,4 All treated women require follow-up to detect residual or recurrent disease, and the ability to distinguish high and low risk women for treatment failure would allow more rational protocols to be developed.Human papillomavirus (HPV) infection, particularly types 16 and 18, has been associated with the occurrence of CIN. 6 Among women with low-grade cervical smear abnormalities, high-risk HPV types are associated with high-grade underlying CIN. [7][8][9] In screened women, persistence of HPV infection has been found to be associated with a greatly increased risk of developing CIN. 10 It has been suggested that, since HPV is detected in many asymptomatic low grade CIN lesions and only a minority of persistent HPV infections progress to cancer, additional factors are necessary if malignant change is to occur. 11 One possible factor may be the exposure to chemical carcinogens such as those present in cigarette smoke. Smoking appears to be the most important factor affecting the progress of CIN after HPV infection. 12 Epidemiological evidence has already implicated cigarette smoking as a possible contributing factor to the development of cervical neoplasia. 13 Smokers have a 4-fold increased risk of developing cervical cancer compared to non-smokers. 14 Smoking is associated with the occurrence of high grade of CIN in the presence of mild dyskaryosis...

Objectives: Vaginal pH is related to hormonal status, and adolescents experience disturbed hormonal patterns following menarche. We assessed hormonal factors and risk of abnormal vaginal pH and bacterial vaginosis (BV) among adolescents attending genitourinary medicine (GUM) clinics. Methods: In a cross sectional study adolescents within 5 years of menarche, (17 years, or with oligoamenorrhoea were recruited. Vaginal pH and BV were assessed and among those not using hormonal contraceptives, estrone-3-glucuronide (E3G) and pregnanediol-3a-glucuronide (P3G) concentrations were measured. Results: Among 102 adolescents, 59.8% (61) had a high vaginal pH (.4.5), which was higher than the prevalence of BV, detected in 33% (34). No association was found between presence of sexually transmitted infections (STI) and vaginal pH. In logistic regression, after controlling for BV and condom use, vaginal pH was positively associated with cervical ectopy (OR = 2.5; 95% CI 1.0 to 6.6, p = 0.05) and STI treatment history (OR = 2.5; 95% CI 0.9 to 6.5, p = 0.07), and negatively associated with use of DepoProvera (OR = 0.1; 95% CI 0.03 to 0.6, p = 0.003) and recent onset (,12 months) of sexual activity (OR = 0.2; 95% CI 0.1 to 0.7, p = 0.004). Among 23 adolescents not using hormonal contraceptives, a high pH occurred more often in abnormal compared to normal menstrual cycles (OR = 10.8; 95% CI 1.4 to 85.4; p = 0.026). E3G concentrations were inversely correlated with vaginal pH in the follicular phase (Spearman: r = 0.51; p = 0.024). Conclusions: Ectopy and abnormal menstrual cycles are common features of adolescence. Their presence is associated with increased risk of abnormal pH, and may also predispose to BV.

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A cluster of five patients with endometrial carcinosarcoma (malignant mixed Müllerian tumor) occurred at our center during 1993; four of these had been prescribed long-term tamoxifen for breast carcinoma. Searching the archives for the 9-year period 1983-1992 revealed two further cases of uterine carcinosarcoma occurring in patients prescribed tamoxifen, from a total of 16 cases of this tumor. Five of the six patients diagnosed with carcinosarcoma who had been taking tamoxifen had been maintained on the drug for at least 6 years, while the other had a 3-year history of tamoxifen therapy. From these data we raise the question of an association between long-term tamoxifen treatment and development of endometrial carcinosarcoma, following the dramatic increase in the prescribing of this drug after 1984.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

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