[Prevalence of genotype-specific HPV infection among women in France: implications for screening and vaccination]. / Prévalence des génotypes d'HPV chez les femmes en France : implications pour le dépistage et la vaccination.

OBJECTIVES: To assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies. PATIENTS AND METHODS: Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with ASC-US+ and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 o'clock positions of the normal transformation zone. RESULTS: Of the 5002 women, 515 (10.3 %) were less than 25 and 4487 (89.7 %) were 25 years old or more. Overall HPV prevalence was 10.1 % to 16.1 % depending on the assay. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2 % and 2.7 % in women less than 25 and 25 years old or more, respectively. HPV 16 was the type most strongly associated with a diagnosis of CIN3+ (odds ratio=11.64 versus HPV 16 absent, P<0.001). A high proportion of high-grade cervical lesions (60.6 % of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58. DISCUSSION ET CONCLUSION: These data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the need for future vaccines to target a wider range of HPV types.

Cervical cancer prevention - current perspectives.

This report addresses several areas including the progress made toward global implementation of currently licensed human papillomavirus (HPV) vaccines, and monitoring impact of HPV vaccination programs that can be implemented within developed and less-developed countries. For the sake of completeness, a short update on the evolution of HPV testing in primary screening programs at present and after HPV vaccine introduction has also been included.

[Perception and psychological impact of an abnormal Pap smear. Results of a comparative European survey]. / Perception et impact psychologique du frottis anormal en France. Résultats comparatifs d'une enquête européenne.

OBJECTIVES: The availability of information on HPV and Pap tests has increased dramatically with the introduction of national HPV vaccination programs. But data on the effectiveness of this information is limited. However, our desire is to reduce patient anxiety and promote better delivery of information. PATIENTS AND METHODS: Therefore a questionnaire-based cohort study was conducted to investigate women's experience with the announcement of an abnormal Pap smear result, then the ensuing events, as well as their practitioner's management. This article focuses on the French experience, underpinned by comparative data with Spain and Portugal. RESULTS: It shows that, face with stress reactions and patient's anxiety, the level of information from the medical profession is still seen as inadequate, while the Internet as an information source has its limitations and dangers. The close entourage is most relied on, which supports the need for better public information. DISCUSSION AND CONCLUSION: Uniformity and standardization of information strategies is not yet on European time.

End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age.

BACKGROUND: Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years. METHODS: We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations. RESULTS: Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported. CONCLUSIONS: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type.

Benefits of vaccinating young adult women with a prophylactic quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine.

Cervical cancer is a leading cause of cancer-related deaths worldwide. The causal role of human papillomavirus (HPV) infection in the pathogenesis of cervical cancer has prompted the development of vaccines against HPV. The highest risk of HPV infection is in women aged 16-25 years. Almost all young adult women can benefit from HPV vaccination. There is strong epidemiological and clinical support for vaccination programmes that target sexually active women in this age group to prevent HPV infection, and thus avert the development of HPV-related disease. Furthermore, the implementation of HPV vaccination programmes may benefit the development or awareness of cervical cancer prevention strategies and ultimately reduce the burden of cervical cancer and improve cervical cancer control.

[Anal cancer and human papillomaviruses: a perspective based on the cervical cancer model]. / Cancer anal et papillomavirus humains: une pathologie en miroir de celle du cancer du col utérin.

Anal cancer is a rare pathology in the general population but the incidence of this cancer has been on the rise for certain high-risk groups, such as homosexual men and immunodepressed subjects. The incidence of anal cancer is 10 times higher in the HIV-positive population than in the female population in general. Moderate to severe dysplasias (AIN2-3) are types of precancerous lesions that usually precede the appearance of the cancer. HPV16 infection is the most common (3/4 of the cases) followed by HPV18 (less than 10%). In anal cancer, HPV16 is present in over 75% of the cases. The prevalence of HPV in anal cancer is higher in women (90%) than in men (75%). Squamous cervical and anal cancers have strong similarities founded on the causal association to HPV, in particular HPV16. Recent data indicate that anti-HPV vaccination has a significant potential in preventing HPV infections, precancerous lesions, and anal cancer in the general population as well as in the high-risk groups.

[Anogenital warts incidence, medical management and costs in women consulting gynaecologists in France]. / Incidence, prise en charge et coût des condylomes acuminés anogénitaux chez les femmes consultant leur gynécologue en France.

OBJECTIVES: The objectives of this study were to estimate the incidence of genital warts and treatment costs in women consulting gynaecologists in France in 2005. PATIENTS AND METHODS: A prospective observational study was performed through a representative sample of gynaecologists. Investigators enrolled all patients seen with genital warts during a 2-month period. A questionnaire detailing socio-demographic characteristics, case description, patient's clinical profile, past/ current management, and treatment of genital warts was completed by the investigators. RESULTS: 212 gynaecologists participated in the study. Questionnaires were completed for 263 patients including 198 (75.3%) new cases, 53 (20.2%) recurrent cases and 12 (4.5%) resistant cases. The overall incidence was estimated at 228.9/100,000 (female 15-65year old population) corresponding to 47,755 cases annually managed by gynaecologists in France. The average treatment cost was 482.70euro for society and 342.40 euro for third-party payers. The annual direct cost of genital warts management was estimated at 23,051,339euro, of which 16,351,312euro was funded by the French health care system. DISCUSSION AND CONCLUSION: The costs of treating genital warts are considerable. The introduction of a quadrivalent (type 6,11,16,18) Human Papillomavirus vaccine including types responsible for 90% of genital warts could potentially substantially reduce these costs.

Current direction in the prevention of cervical cancer.

Cervical screening seems to benefit a minor part of the world female population, and yet women who benefit from it still prove its weaknesses. The fact that these genital lesions are the consequence of a chronic genital infection with HPV opens new and extraordinary opportunities for prevention through vaccination. The highest efficacy is demonstrated in young women naive to the virus types associated with the vaccines. The effectiveness of HPV vaccines are limited by two factors: all genital cancers and precancerous lesions are not induced exclusively by HPV types 16 and 18, and the optimal benefit is demonstrated in adolescents and young women before they have encountered these viruses. Vaccination and screening act complementarily and synergistically, and constitute to date the new standards of disease prevention.

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia.

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.

Ano-rectal lymphogranuloma venereum: 22 cases reported in a sexually transmited infections center in Paris.

In January 2004 the European Surveillance of Sexually Transmitted Infections Network (ESSTI) issued an international alert regarding an outbreak of Lymphogranuloma venereum (LGV) in Rotterdam in a sexual network of men who have sex with men (MSM). Further to this alert, a retrospective survey was set up by the Institut de Veille Sanitaire and the reference laboratories for N.gonorrhoeae and Chlamydia in France. Our STI clinic in Paris carried out a clinico-biological retrospective study involving 154 MSM screened for anorectal sexually transmitted infections (STIs) between January 2002 and May 2004 and a prospective study between May 2004 and August 2004. Out of 216 swabs of rectal discharge from homosexual or bisexual males, a total of 32 were positive for C. trachomatis (14.8%) (3 patients in 2002, 11 in 2003 and 18 in 2004). C. trachomatis-positive rectal strains were genotyped to detect the specific C. trachomatis serovars and revealed serovars L(2) for 22 patients (respectively 1 in 2002, 9 in 2003 and 12 in 2004). Serum antibody titers for Chlamydia trachomatis were determined among 14 subjects and revealed strongly positive in 13 cases (1/512 to 1/16384) titers of IgG. These 22 patients with clinico-biologically confirmed anorectal lymphogranuloma venereum (ARLGV) were all homosexual men. They ranged from 28 to 52 years (mean age 39.2 years). 12 of 21 (57.1%) subjects with an ARLGV diagnosis were seropositive for human immunodeficiency virus (HIV) (one not done). Although rare, anorectal lymphogranuloma venereum (ARLGV) still exists in France and should not be forgotten in the differential diagnosis of rectal problems in male homosexuals.

[Cervical cancer prevention: the impact of HPV vaccination]. / Prévention du cancer du col utérin: enjeux et perspectives de la vaccination antipapillomavirus.

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. In spite of the success of cervical cancer screening, Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. The establishment of Human Papillomavirus (HPV) infection as the necessary cause of cervical precancers and cancers provides a tremendous opportunity for cervical cancer prevention through vaccination. HPV 16 and 18 which cause 70% of cervical cancers worldwide. Thus a prophylactic vaccine to prevent HPV related precancerous lesions and cancers would save lives, reduce the need for costly medical procedures and provide both women and communities throughout the world with substantial benefits. Based on the induction of neutralizing antibodies by non infectious Virus Like Particles (VLP) of L1 capside protein, prophylactic HPV vaccines have consistently induced high titter of neutralizing antibodies with minimal side effects and induce more than 90% protection from persistent HPV 16-18 infection and HPV 16 and 18 associated high-grade Cervical Intraepithelial Neoplasia (CIN) in proof of concept efficacy trials. HPV 16-18 vaccination will prevent HPV16-18 incident infection, and subsequently decrease in 90% the frequency of abnormal Pap attributable to these types and in about 50% overall abnormal Pap. HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. The level of protection from death due to cervical cancer could exceed 95%. Three large phases prophylactic HPV VLP trials are now in progress and will form the basis for licensing of candidate vaccines in 2006. HPV vaccination targeting young female adolescents, aged 11 to 16 years, with a catch-up of those aged 17-25 years, would be a strategy to be addressed. Cervical cancer screening strategies, that will be cost-effective for the proper surveillance of women protected by HPV vaccination, are under analysis.

[Colposcopy: the value of HPV testing in clinical practice]. / Colposcopie : apport du test HPV en pratique clinique.

The indications for colposcopy have changed recently because of the new Bethesda terminology, the introduction of HPV testing in clinical practice, and the latest consensus guidelines on management of patients with an abnormal cervical cytological test. Colposcopy remains the reference technique to assess patients with abnormal cytological test results, especially those with ASC-H, LSIL, HSIL, and AGC. In women with an ASC-US result, colposcopic examination of only those who test positive for high-risk HPV increases the specificity of the technique. When liquid-based cytology is used, HPV DNA testing is the preferred approach in these women. In primary screening using combined cytology and HPV DNA testing in women over the age of 30, colposcopy is indicated in patients with normal cytology and two HR HPV DNA positive tests performed at a nine month interval. For the follow up of untreated patients with ASC-US/LSIL and CIN I, colposcopy carried out at one year after a single HR HPV DNA positive test is as sensitive as colposcopy after two or three abnormal cytology tests. After excision or conization in patients with high-grade CIN, colposcopy after a single HR HPV DNA positive test is as sensitive as cytology testing and colposcopy at six months. Therapeutic decisions must not be based solely on the results of HPV DNA testing except in specific cases.

[A model-based comparison of cost effectiveness of imiquimod versus podophyllotoxin for the treatment of external anogenital warts in France]. / Comparaison coût-efficacité par modélisation de l'imiquimod et de la podophyllotoxine dans le traitement du condylome acuminé externe en France.

OBJECTIVES: For the National health scheme, to compare the costs and the efficacy of treatment of external anogenital warts with imiquimod and podophyllotoxin and laser therapy in the case of failure or relapse. PATIENTS AND METHODS: A model simulating the two successive treatments was built. In the first phase, the two topical treatments applied by the patients: podophyllotoxin for 4 weeks and imiquimod for 16 weeks were compared. In the case of failure or relapse, laser therapy that is widely used in France in this indication and, was applied. The efficacy of the topical treatments was assessed after reanalysis of the results of two controlled clinical trials versus placebo. These two trials were retained because they were comparable in method and had been recently published at the same time. A review of the literature assessed the results of laser therapy. A survey was conducted to collect the medical resources consumed by the different treatments. RESULTS: Imiquimod provided a clearance rate of 49.5 p. 100, i.e., the disappearance of the lesions at 16 weeks, greater than that of podophyllotoxin (28.3 p. 100) at 4 weeks. The relapse rate was lowest with imiquimod (13.3 p. 100) than with podophyllotoxin (30.9 p. 100). The remission rate without relapse 3 months after the end of treatment was, including the laser, of 62 p. 100 following imiquimod and of 47 p. 100 following podophyllotoxin. The costs per patient cured was of 668 Euros for imiquimod and of 689 Euros for podophyllotoxin. CONCLUSION: Imiquimod, because of its greater initial efficacy, is at least as cost-effective as podophyllotoxin the treatment of external genital warts.