Epidemiological, clinical, and virological characteristics of women with genital warts in Greece.

This is a prospective study of the epidemiological, clinical, and virological characteristics of cases of genital warts in a Greek University Hospital. The women completed a questionnaire regarding their medical and sexual history and underwent cervical cytology, HPV DNA typing, mRNA testing, colposcopy, Chlamydia testing, and proctoscopy. Univariate and multivariate analyses were performed. The most commonly detected types were type 6 (36.1%) and 16 (24.3%). E6/E7 mRNA testing was positive in 21.5%. Concurrent cervical intraepithelial neoplasia grade 2 or worse was found in 11.1% and intra-anal warts in 10.4%. For chlamydial infection the number of sexual partners was a significant predictor. Women with warts infected with types 6 and 11 constituted only 37.5% of the total. This could have a negative effect on the efficacy of vaccination in reducing the incidence of the disease. Based on the present findings the authors recommend cytology and colposcopy for all women with genital warts.

The role of p16(INK4a) immunostaining in the risk assessment of women with LSIL cytology: a prospective pragmatic study.

BACKGROUND: The detection of high-grade cervical intraepithelial neoplasia (CIN2 or worse) among patients with low-grade cytology (LSIL) is challenging. The aim of this study was to assess the efficacy of p16(INK4a) in the risk assessment of women with LSIL cytology. METHODS: Consecutive liquid-based cytology specimens of 95 LSIL smears were selected and stained for p16(INK4a). All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2 or worse. RESULTS: The overall sensitivity and specificity of p16(INK4a) for diagnosis of CIN2+ among LSIL smears were 41% and 86%, respectively. The positive predictive value of the biomarker was 62% and the negative predictive value 72%. CONCLUSIONS: The study shows that p16(INK4a) has low sensitivity but acceptable specificity for evaluation of LSIL smears harbouring high-grade lesions. The marker needs to be further assessed as an adjunct to other tests in an attempt to improve the triage of LSIL cytology smears.

Women's knowledge and utilization of gynecological cancer prevention services in the Northwest of Greece.

PURPOSE OF INVESTIGATION: In Greece an organized cervical or breast cancer screening program does not exist and the population coverage is unknown. METHODS: Women of all ages completed a questionnaire, which assessed women's awareness of and participation in breast and cervical screening and human papillomavirus (HPV) vaccination. The women were randomly approached in public areas. RESULTS: 1,012 women completed the questionnaire. 52% of the women over 39 years old had undergone mammography in the last year and 76% of the women over 20 years old had a cervical smear test within the last three years in an opportunistic basis. In addition, the likelihood of having regular mammograms was positively associated with the likelihood of having regular cervical smears. Fifty percent of the responders did not identify HPV as the cause of cervical cancer and 38% were not aware of the HPV vaccine. From the women aged 16 to 28 years old, 11% had been vaccinated against HPV and an additional 23% intended to have the vaccine in the next six months. CONCLUSION: Knowledge and utilization of mammography and cervical screening was quite satisfactory, although HPV vaccination coverage was low. Preventive services could be improved through the development of a plan for the information of the public and the distribution of the HPV vaccine.

High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a prospective diagnostic study.

OBJECTIVE: The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR-HPV positive LSIL. METHODS: We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16(INK4a) immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+. RESULTS: A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89% (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone (p=0.4). CONCLUSIONS: The results indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL.

Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia.

OBJECTIVE: This study aims to assess the alterations in various HPV-related biomarkers 6 months post-treatment and how these relate to various risk factors and individual characteristics; their role for the prediction of treatment failure was also evaluated. DESIGN: Prospective observational study. POPULATION: Women planning to undergo treatment for cervical intraepithelial neoplasia. INTERVENTION: A liquid-based cytology sample was taken pre-operatively. This was tested for HPV genotyping, Nucleic Acid Sequence Based Amplification, flow cytometric evaluation and p16 immunostaining. A repeat LBC sample was obtained 6 months post-treatment and was tested for the same biomarkers. OUTCOMES: The alterations of the biomarkers 6 months post-treatment were recorded. Their relation to individual characteristics and risk factors (age, smoking, sexual history, use of condom, CIN grade, excision margin status, crypt involvement) as well as their role for the prediction of residual/recurrent disease were assessed. ANALYSIS: The accuracy parameters (sensitivity, specificity, positive and negative predictive value and the likelihood ratios) of each biomarker for the prediction of recurrent/residual CIN were calculated. RESULTS: A total of 190 women were recruited. All biomarkers had significantly higher negativity rates post-treatment compared to pre-treatment ones. Multivariate analysis demonstrated that consistent condom use post-treatment significantly reduces the high-risk HPV positivity rates in comparison to no use (OR=0.18; 95% CI: 0.09-0.38). Sensitivity and specificity for all high risk HPV DNA testing were 0.5/0.62, respectively; the relevant values for only type 16 or 18 DNA typing were 0.5/0.92, for NASBA 0.5/0.94, for flow 0.5/0.85 and for p16 0.25/0.93. CONCLUSION: CIN treatment reduces positivity for all HPV-related biomarkers. Consistent condom use significantly reduces high-risk HPV positivity rates. More cases of treatment failures are required in order to specify whether different combinations of HPV-related biomarkers could enhance the accuracy of follow up, possibly in the form of a Scoring System that could allow tailored post-treatment surveillance.

Clinical management of HPV-related disease of the lower genital tract.

Cytology remains the mainstay for cervical screening. The need to achieve effective management, limit complications, and preserve reproductive function led to the popularity of local treatment. Although the cure rates for ablative and excisional methods are similar, the excisional method provides a more reliable histopathological diagnosis. Recent evidence revealed increased perinatal morbidity after treatment that appears to be related to the proportion of cervix removed. The human papillomavirus (HPV) DNA test appears to enhance the detection of disease in primary screening, in the triage of minor cytological abnormalities, and in follow-up. Further research on the clinical application of a scoring system is ongoing. The vaccines are now available and appear to be safe, well tolerated, and highly efficacious in HPV naive women. A synergy of vaccination and screening will be required. Treatment for early cervical cancer is increasingly shifting toward more fertility-sparing surgical techniques. Careful selection of patients is essential.

Proportion of excision and cervical healing after large loop excision of the transformation zone for cervical intraepithelial neoplasia.

OBJECTIVE: To determine how the proportion of the cervical volume excised affects cervical regeneration. DESIGN: Prospective observational study. SETTING: University Hospital. POPULATION: Women planning to undergo excisional treatment for cervical intraepithelial neoplasia who wish to have future pregnancies. METHODS: The cervical volume (and dimensions) is calculated with magnetic resonance imaging (MRI) before treatment. The volume (and dimensions) of the cone is assessed before fixation by a volumetric tube and a ruler; the percentage (%) of excision is computed. Cervical regeneration is estimated by repeat MRI at 6 months. MAIN OUTCOME MEASURES: Cervical regeneration in relation to proportion of excision. Statistical analysis was performed by box plots and analysis of variance. RESULTS: A total of 48 women have been recruited; 29 have completed 6 months follow up. Both the total cervical volume (from MRI) before treatment and the volume of the excised/ablated cone varied substantially. The estimated proportion of excision varied significantly between 4% and 39% (median 11%). Multivariate linear regression revealed that the proportional deficit at 6 months post-treatment was determined mainly by the proportion of the excised volume. CONCLUSIONS: Careful assessment of risks and benefits of treatment is essential when deciding to treat women who wish to have future pregnancies. Assessment of the proportion of the cervical volume and length excised might identify those that need further surveillance during future pregnancy.