Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation.

OBJECTIVES: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

BACKGROUND: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. METHODS: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. RESULTS: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. CONCLUSIONS: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India.

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.

Diagnostics, surveillance and management of sexually transmitted infections in Europe have to be improved: lessons from the European Conference of National Strategies for Chlamydia Trachomatis and Human Papillomavirus (NSCP conference) in Latvia, 2011.

BACKGROUND: There is an urgent need for the recognition of sexually transmitted infections (STIs) as a serious public health problem in Europe. The lack of standardization in testing, along with poor reporting and surveillance mechanisms, have resulted in low reported rates of STIs in many European Union (EU) countries, reinforcing the erroneous assumption that STIs are not a major problem. Testing and diagnosis of STIs must therefore be improved and enhanced. RECOMMENDATIONS: Reporting of Chlamydia trachomatis infection, gonorrhoea and syphilis should be mandatory, and an integrated surveillance system for C. trachomatis implemented in all European countries. Implementation of the European Centre for Disease Prevention and Control (ECDC) surveillance mechanisms for STIs in all EU countries is highly recommended. A necessary component for successful introduction of the HPV vaccine, as with any vaccination programme is a well-planned and organized information campaign.

Increased detection of the HIV-1 reverse transcriptase M184V mutation using mutation-specific minority assays in a UK surveillance study suggests evidence of unrecognized transmitted drug resistance.

OBJECTIVES: The aim of the study was to estimate the levels of transmitted drug resistance (TDR) in HIV-1 using very sensitive assays to detect minority drug-resistant populations. METHODS: We tested unlinked anonymous serum specimens from sexual health clinic attendees, who had not received an HIV diagnosis at the time of sampling, by both standard genotyping and using minority detection assays. RESULTS: By standard genotyping, 21 of 165 specimens (12.7%) showed evidence of drug resistance, while, using a combination of standard genotyping and minority mutation assays targeting three commonly observed drug resistance mutations which cause high-level resistance to commonly prescribed first-line antiretroviral therapy (ART), this rose to 32 of 165 (19.4%). This increase of 45% in drug resistance levels [95% confidence interval (CI) 15.2-83.7%; P=0.002] was statistically significant. Almost all of this increase was accounted for by additional detections of the M184V mutation. CONCLUSIONS: Future surveillance studies of TDR in the United Kingdom should consider combining standard genotyping and minority-specific assays to provide more accurate estimates, particularly when using specimens collected from chronic HIV infections in which TDR variants may have declined to low levels.

Men who have sex with men and women in Bangalore, South India, and potential impact on the HIV epidemic.

OBJECTIVE: The aim of this study was to quantify differences in patterns of sexual behaviour among men who have sex with men and women (MSMW) compared with men who have sex with men only (MSMO), and to examine the extent to which bisexual behaviour may act as a bridge for introducing HIV infection into the general population. METHODS: A cross-sectional survey in Bangalore city in 2006, which sampled men seeking sex with men in public places and hammams (bath houses where transgender individuals sell sex to men). RESULTS: Among a sample of 357 men reporting same-sex behaviour; 41% also reported sex with a woman in the past year and 14% were currently married to a woman, only two of whom had informed their wives about having sex with men. Condom use was very inconsistent with all male partners, while 98% reported unprotected vaginal sex with their wives. MSMW reported lower rates of risky behaviour with other men than MSMO: fewer reported selling sex (17% vs 58%), or receptive anal sex with known (28% vs 70%) or unknown (30% vs 59%) non-commercial partners. CONCLUSION: Bisexual behaviour was common among men seeking sex with men sampled in this survey. Although MSMW reported lower rates of risky sexual behaviour with male partners than MSMO, inconsistent condom use with both male and female partners indicates a potential means of HIV transmission into the general population. HIV prevention programmes and services should reach bisexual men who potentially expose their male and female partners to HIV.

Assessment of intervention outcome in the absence of baseline data: 'reconstruction' of condom use time trends using retrospective analysis of survey data.

BACKGROUND: Avahan, the India AIDS Initiative, is a large-scale targeted intervention. Data on condom use prior to Avahan are unavailable. The authors used a novel method of analysing cross-sectional survey data to 'reconstruct' condom use rates in presurvey years, and to assess the relationship between Avahan and time trends in condom use among female sex workers (FSWs). METHODS: Among FSWs reporting consistent condom use (CCU) with clients in surveys from 21 districts in southern India (n=7358), data on length of time using condoms, and length of time selling sex, were converted into number of FSWs using condoms (numerator) and selling sex (denominator) by year, to give yearly rates of CCU from 2001 to year of survey. Linear regression with generalised estimating equations was used to assess time trends and to compare the rate of increase in condom use before and after Avahan initiation in 2003. RESULTS: In all 21 districts, the rate of increase in CCU from 2001 to time of the surveys was highly significant. Overall CCU increased from 27% (22%) with occasional (regular) clients in 2001, to 76% (68%) in 2006, respectively. The yearly rate of increase in CCU was significantly greater after (slope 2003-2006: 12.7% (12.0%) per year for occasional (regular) clients) than prior to Avahan (slope 2001-2003: 5.1% (5.3%) per year for occasional (regular) clients) implementation (p<0.0001). CONCLUSIONS: The findings indicate a positive relationship between implementation of the Avahan programme and rates of CCU increase among FSW. This method of analysis may be useful in other contexts where preintervention data are lacking.

Lymphogranuloma venereum in Europe, 2003-2008.

Lymphogranuloma venereum, caused by the L serovars of Chlamydia trachomatis, emerged in Europe in 2003 and a series of outbreaks were reported in different countries. The infection presents as a severe proctitis in men who have sex with men, many of whom are co-infected with HIV and other sexually transmitted infections. This paper reviews the number of cases reported over a five year period, from 2003 to 2008, from countries that were part of the European Surveillance of Sexually Transmitted Infections (ESSTI) network. Reports were received from Belgium, Denmark, France, Germany, the Netherlands, Portugal, Spain, Sweden, and the United Kingdom. It appears that after five years the characteristics of the patients infected has overall remained unchanged, although the total number of cases has increased and more countries in Europe have now identified cases of LGV.

Syphilis and gonorrhoea in men who have sex with men: a European overview.

This paper describes recent trends in the epidemiology of syphilis and gonorrhoea infections in Europe among men who have sex with men (MSM). Routine surveillance data submitted to the European Surveillance of Sexually Transmitted Infections (ESSTI) network from 24 European countries for the period 1998-2007 were analysed. Data on whether syphilis and gonorrhoea infections were in MSM were available for 12 and 10 countries respectively. The number of syphilis cases reported to be MSM increased considerably in all Western European countries. While in some Central and Eastern European countries the male to female ratio remained relatively stable at around 1:1, in Slovenia and Czech Republic the proportion of male cases increased and so did the percentage of cases reported to be MSM. More cases of gonorrhoea were seen in men than women, but the percentage of male cases reported to be MSM was lower than for syphilis. The findings suggest MSM are at high risk of STI in Western Europe and appear to be an increasingly important risk group in Central Europe. Despite this, data on infections among MSM are not collected routinely in many countries. The introduction of standardised data collection including data on diagnoses in MSM should be prioritised for monitoring STI in this population.

Epidemiology of herpes simplex virus types 2 and 1 amongst men who have sex with men attending sexual health clinics in England and Wales: implications for HIV prevention and management.

The objective was to investigate herpes simplex virus (HSV) epidemiology amongst HIV-positive and HIV-negative men who have sex with men (MSM) in England and Wales. Unlinked anonymous sera from 3,968 MSM attending 12 sexual health clinics in 2003 were tested for HIV, HSV-2 and HSV-1 antibodies. Fifty-five percent of HIV-positive MSM were HSV-2-seropositive, compared to 17% of HIV-negative MSM (Adj RR: 2.14 [CI: 1.92-2.37]). Amongst HIV-positive individuals, there was no significant difference in HSV-2 seroprevalence by knowledge of HIV status or whether the HIV infection was recently acquired (determined through STARHS). HIV infection was also independently associated with HSV-1 serostatus (Adj RR 1.19 [CI: 1.14-1.24)]). Four of the twelve attendees who received a diagnosis of recurrent anogenital herpes at the clinic visit were HSV-1-seropositive but not HSV-2-seropositive at the time, although no cultures or PCR results were available to type the cause of the ano-genital presenting disease. It is of concern that one in two HIV-positive MSM and one in six HIV-negative MSM may be infected with HSV-2, given increasing evidence of its impact on HIV progression, onward transmission and acquisition. To date results have been disappointing from trials aimed at reducing HIV onward transmission and HIV acquisition using HSV antiviral medication. However, recent research in an African context demonstrates the efficacy of HSV antivirals in delaying HIV progression. The high prevalence of HSV-2 amongst HIV-positive MSM suggests that an increased focus on HSV control in the management of HIV amongst MSM in the United Kingdom may be warranted. Given this and existing research on the high prevalence of genitally acquired HSV-1 amongst MSM in the UK, further research is also warranted into the role of HSV-1 in the HIV epidemic in this context.

National study of HIV testing in men who have sex with men attending genitourinary clinics in the United Kingdom.

OBJECTIVES: To determine what proportion of men who have sex with men (MSM) attending genitourinary medicine (GUM) clinics are offered and accept an HIV test and to examine clinic and patient characteristics associated with offer and uptake. METHODS: A cross-sectional study of all GUM clinics in the United Kingdom, involving a case note review of up to 30 patient records per clinic and the completion of a clinic policy form. RESULTS: Overall, 86% of MSM were offered a test and of those 82% accepted a test. Attending with symptoms of a sexually transmitted infection (STI), fewer numbers of partners in the past three months and having tested previously were all independently associated with a decreased likelihood of being offered a test. Attending with symptoms of an STI, increasing age, never having had a risk from unprotected anal intercourse or a previous HIV test and increasing time to wait for results were all independently associated with a decreased likelihood of a patient accepting a test. Only a quarter of clinics reported a written policy for HIV testing intervals among MSM; however, all clinics reported offering testing to all new MSM patients at first screening. The testing policy for re-attending patients was less clear. CONCLUSIONS: Testing must reach those at most risk and those less likely to test in order to reduce further the proportion of undiagnosed HIV infection. This study suggests that opportunities to detect infection may be being missed and a move towards universal testing of all MSM attending with a new episode, as well as testing within the window period, is recommended.

Sexual identity and its contribution to MSM risk behavior in Bangaluru (Bangalore), India: the results of a two-stage cluster sampling survey.

In India, there are categories of MSM (hijras, kothis, double-deckers, panthis and bisexuals), which are generally associated with different HIV-risk behaviors. Our objective was to quantify differences across MSM identities (n = 357) and assess the extent they conform to typecasts that prevail in policy-orientated discourse. More feminine kothis (26%) and hijras (13%) mostly reported receptive sex, and masculine panthis (15%) and bisexuals (23%) insertive anal sex. However, behavior did not always conform to expectation, with 25% and 16% of the sample reporting both insertive and receptive anal intercourse with known and unknown noncommercial partners, respectively (p < 0.000). Although behavior often complied with stereotyped role and identity, male-with-male sexual practices were fluid. Reification of these categories in an intervention context may hinder our understanding of the differential HIV risk among MSM.

Interventions among male clients of female sex workers in Benin, West Africa: an essential component of targeted HIV preventive interventions.

OBJECTIVES: To assess the impact of interventions targeted towards female sex workers (FSWs) and their male clients on client HIV/STI prevalence and sexual behaviour. METHODS: From 1993 to 2006, an HIV/STI preventive intervention focusing on condom promotion and STI care was implemented among FSWs in Cotonou, Benin, and then expanded to cover their male sexual partners in 2000. The interventions were scaled up to five other cities of Benin in 2001-2002. Serial cross-sectional surveys of HIV/STI prevalence and sexual behaviour were carried out among clients in Cotonou in 1998, 2002 and 2005; and in the five other cities (O/Cotonou) in 2002 and 2005. RESULTS: Significant declines in gonorrhoea prevalence among clients of FSWs: Cotonou, from 5.4% in 1998 to 1.6% in 2005; O/Cotonou: from 3.5% in 2002 to 0.59% in 2005. Chlamydia prevalence also declined O/Cotonou, from 4.8% to 1.8%, while HIV prevalence remained stable. Reported condom use by clients with both FSWs and casual non-FSW partners, but not regular partners, increased significantly. While condom use at last sex with an FSW was similar in Cotonou to O/Cotonou around the time of implementation of the interventions (56% in 1998 vs 49% in 2002, respectively), it had risen to similar levels by 2005 (95% and 96%, respectively). CONCLUSIONS: These results demonstrate that it is possible to implement preventive and clinical services for clients of FSWs, and suggest that such interventions, integrated with those targeted towards FSWs, can have a significant effect on sexual behaviour and STI prevalence (particularly gonorrhoea) among this population.

Evaluating large-scale HIV prevention interventions: study design for an integrated mathematical modelling approach.

BACKGROUND: There is an urgent need to evaluate HIV prevention interventions, thereby improving our understanding of what works, under what circumstances and what is cost effective. OBJECTIVES: To describe an integrated mathematical evaluation framework designed to assess the population-level impact of large-scale HIV interventions and applied in the context of Avahan, the Indian AIDS Initiative, in southern India. The Avahan Initiative is a large-scale HIV prevention intervention, funded by the Bill & Melinda Gates Foundation, which targets high-risk groups in selected districts of the six states most affected by the HIV/AIDS epidemic (Maharashtra, Karnataka, Tamil Nadu, Andhra Pradesh, Nagaland and Manipur) and along the national highways. METHODS: One important component of the monitoring and evaluation of Avahan relies on an integrated mathematical framework that combines empirical biological and behavioural data from different subpopulations in the intervention areas, with the use of tailor-made transmission dynamics models embedded within a Bayesian framework. RESULTS: An overview of the Avahan Initiative and the objectives of the monitoring and evaluation of the intervention is given. The rationale for choosing this evaluation design compared with other possible designs is presented, and the different components of the evaluation framework are described and its advantages and challenges are discussed, with illustrated examples. CONCLUSIONS: This is the first time such an approach has been applied on such a large scale. Lessons learnt from the CHARME project could help in the design of future evaluations of large-scale interventions in other settings, whereas the results of the evaluation will be of programmatic and public health relevance.

What is the achievable effectiveness of the India AIDS Initiative intervention among female sex workers under target coverage? Model projections from southern India.

BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk groups such as female and male sex workers and their clients, to limit HIV transmission in the general population. OBJECTIVES: To assess the potential effectiveness of the Avahan intervention at the level of coverage targeted, in different epidemiological settings in India. METHODS: A deterministic compartmental model of the transmission dynamics of HIV and two sexually transmitted infections, and sensitivity analysis techniques, were used, in combination with available behavioural and epidemiological data from Mysore and Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic sexually transmitted infection (STI) management (STI treatment), periodic presumptive treatment of STI (PPT), and condom components of the Avahan intervention targeted to female sex workers (FSW). RESULTS: If all components of the intervention reach target coverage (that is, PPT, STI treatment and condom use), the intervention is expected to prevent 22-35% of all new HIV infections in FSW and in the total population over 5 years in a low transmission setting like Mysore, and to be half as effective in high transmission settings such as Bagalkot. The results were sensitive to small variations in intervention coverage. The condom component alone is expected to prevent around 20% of all new HIV infections over 5 years in Mysore and around 6% for the STI component alone; compared with 7%-14% for the PPT component alone. Multivariate sensitivity analyses suggested that interventions may be more effective in settings with low FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The Avahan intervention is expected to be effective. However, to be able to demonstrate effectiveness empirically in the different settings, it is important to achieve target coverage or higher, which in the case of PPT could take a number of years to achieve. These preliminary model predictions need to be validated with more detailed mathematical models, as better data on sexual behaviour, condom use, STI and HIV trends over time, and intervention coverage data accumulate over the course of the programme.

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

Comparability of laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae from reference laboratories in Western Europe.

OBJECTIVES: The aim of this study was to obtain information on the comparability of methods for the laboratory diagnosis of bacterial sexually transmitted infections (STIs) that contribute to the surveillance data in the European Union (EU) and Norway. Surveillance of bacterial STIs is important across Europe because of the movement of individuals between countries at a time when STI incidence appears to be increasing in many countries. METHODS: Cross-sectional survey using a questionnaire, to provide information on laboratory methods for the diagnosis of gonorrhoea, and a panel of strains of Neisseria gonorrhoeae, to compare susceptibility testing, was circulated to laboratories in the EU and Norway. RESULTS: The questionnaire revealed marked diversity in the methodologies used for the laboratory diagnosis of gonorrhoea across Europe. Fourteen laboratories participated in an exchange of gonococcal strains to assess the methodology in current use for susceptibility testing. The methods included disc diffusion and determination of the minimum inhibitory concentration (MIC) using agar dilution and/or Etest. There was no common method used, each centre varied from another by at least one procedure. Overall agreement using all methods was >70%, being highest for ceftriaxone and lowest for tetracycline. Disc diffusion gave the lowest agreement with the consensus compared with determination of MIC by either agar dilution or Etest. CONCLUSIONS: A variety of methods were used across the EU and Norway for the laboratory diagnosis and susceptibility testing and resulted in poor concordance between laboratories on the definition of resistant N. gonorrhoeae. This suggests that there is a need for greater standardization of methodology that provides surveillance data in the EU and Norway.

Vaccines for cervical cancer.

The review focuses on current and future prevention of invasive cervical cancer (ICC), the second most common cancer among women worldwide. Implementation of population-based cytological screening programmes, using the 'Pap' smear to detect pre-cancerous lesions in the cervix, has resulted in substantial declines in mortality and morbidity from ICC in North America and some European countries. However, cases of, and deaths from, ICC continue to occur. Primary prevention of infection with high-risk human papillomavirus (HPV) types, the central causal factor of ICC, could further reduce incidence of and mortality from ICC. This is particularly the case in developing countries, which bear 80% of the burden of ICC, and where effective Pap screening programmes are extremely difficult to implement. Very promising results from several trials of synthetic HPV type-specific monovalent (HPV 16) and bivalent (HPV 16 and 18) vaccines have recently been published, showing high efficacy against type-specific persistent HPV infection and development of type-specific pre-cancerous lesions. Large-scale phase III trials of a number of such vaccine candidates are currently underway, and there is real hope that an effective vaccine capable of protecting against infection with HPV types 16 and 18 (which together account for approximately 70% of cervical cancer cases worldwide), and thereby of preventing development of a very significant proportion of cases of ICC, could be available within the next 2 years.