The First Asia-Oceania Research Organisation on Genital Infectionsand Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia,in July 2005. The conference covered regional issues relating toinfection with the human papillomavirus—epidemiology, virology,and immunology, testing, screening, and prevention strategies—aswell as cervical cancer screening and its management. Cancer prevention and control are among the most important publichealth challenges facing the world today.Worldwide, carcinoma of the uterine cervix is the second mostcommon cancer in women. Incident cases are estimated to beapproximately 470 600 per annum, with almost 80% occurring inthe developing world.The AOGIN concept was based upon an expert multidisciplinary groupdeveloped overseas—the European Research Organisation on GenitalInfection and Neoplasia (EUROGIN).This organisation crosses professional boundaries, unitinggynaecology, sexual health, dermatology, epidemiology/publichealth, pathology, biology, oncology, and basic science.AOGIN aims are to promote and develop research, training,screening, prevention, and information concerning genitalinfections, precancers, and cancers in women.New breakthroughs in diagnostics, treatment, and prevention willprovide both opportunities and challenges in upcoming years. AOGINactivity should assist decision-making and planning so that themost cost-effective gains can be made for each nation.collaboration and research,scientific exchanges, education and training,information provision,surveys and audits.The work will focus onThe first AOGIN Meeting was held in Kota Kinabalu, Malaysia, inJuly 2005. It was coordinated by an executive committee thatincluded leading physicians from Australia, Japan, Korea,Singapore, India, and China.The meeting was generously supported by a number of pharmaceuticaland diagnostic companies, and received helpful input fromprofessional societies. Delegates from 23 nations attended themeeting and gave insights into HPV and cervical cancerepidemiology and management in their countries.Globocan data suggest that around 470 000 cases of cervicalcancer are diagnosed worldwide every year . While tThe relative incidence for different cancers varies significantlybetween regions. In North America, cervical cancer is not amongthe leading seven cancers diagnosed in women, nor among the topseven cancers that result in death.A very different scenario exists in Central/South America , Africa (most frequent cancer diagnosis and causeof death), and Asia (second most frequent cancer diagnosis andfourth most frequent cause of death).It is estimated that the lifetime risk of any woman experiencingcervical cancer is 3–4%. Yet age adjusted rates (AARs) vary from as high as 42.7 in Eastern Africa and 38.2 in Southern Africa, to as low as5.8 in Western Asia .HPV is a small DNA virus that demonstrates significant geneticvariation, with more than 100 types identified and sequenced todate. Two oncogenes associated with the virus have beenidentified, and are known as E6 and E7, which have the ability todegrade the proteins of the cellular genes p53 and Rb, thusinterfering with essential mechanisms of cell proliferation andrepair. A different section of viral DNA has been shown to beimmunogenic and appears to generate a protective response.The pathogenicity of the viruses varies: some types (such as 6 and11) are linked to genital warts, while others (such as 16 and 18)are frequently seen in women diagnosed with invasive cervicalepithelial abnormalities or cancer. Infection does not inevitablylead to pathological changes; regression occurs in some cases.Interestingly, HPV prevalence among the general population issignificantly higher in North-Eastern Africa (34.0%) andCentral/South America (23.5%) than in other regions. In Asia,incidence is higher in the East (13.8%) and South-central(11.9%) areas than in Japan-Taiwan (7.4%) and South-EastAsia (4.9%).n = 2855) indicatesthat although frequencies varied, HPV 16 followed by HPV 18 weremost commonly detected in Africa, Central-South America, SouthAsia, and North America. HPVs 45, 31, and 33 were also seenglobally ..11].Further results from the ALTS study, in which 897 cases oflow-grade squamous intraepithelial lesion (LSIL)and 1193 cases of HPV DNA-positive ASCUS were followed for 2years, suggested that LSIL lesions and HPV-positive ASCUS areclinically equivalent . InitialP = .002), but lessspecific  for detecting CIN2+. Surveillance at 12 months was as effective for monitoringprogression as immediate colposcopy.The HPV in addition to routine testing (HART) study looked at themanagement of women who tested positive for high-risk types ofHPV, but had negative or borderline screening abnormalities. HPV tesA meta-analysis to assess the accuracy of HPV DNA testing as analternative to repeat cytology in women who had equivocal resultson a previous Pap smear suggests that HC II assay has highersensitivity and similar specificity than the repeat Pap smear(ASCUS as threshold) for CIN2+ among women in this patient group.HPV testing has a high negative predictive value and although thepositive predictive value is lower, it offers considerablebenefits in triaging patients. It can also assist decision makingon behalf of women with mild cytological abnormalities.determine the age-specific HPV prevalencein different European areas,evaluate the sensitivity and specificityof HPV testing in women attending routine screening,compare the sensitivity and specificityof HPV testing with that of routine cytology.The objectives for reviewing HPV screening trials were toStudies included were from the UK  as the sole primary screening test for cervical cancer.Due to its automated, highly sensitive, and objective nature,results are less variable and quality control is simpler. Cytologycould thus be reserved for 6–10% of women; screening would beundertaken in more detail by a smaller number of more focusedcyto-screeners. Triage of HPV-negative ASCUS/LSIL lesions would beeliminated.Screening intervals could be longer with potential cost savingsand greater convenience.A 2001 Cochrane report suggests there is no overwhelminglysuperior surgical technique for eradicating CIN .Regardless of treatment approach, the risk of persistent diseaseis greater when the lesion is large, or the patient is > 30 yearsof age or has been treated previously and/or is a carrier of HPVtypes 16 or 18 .Between 1998 and mid-2003, 3647 women were treated at Melbourne'sRoyal Women's Hospital (RWH) for CIN.Among those who returned 3–6 months postsurgery, 21% returnedan abnormal Pap smear/histology. By 9–14 months, persistentlow-grade abnormality was seen in 9.4% and high-gradeabnormality in 0.7% of women.Residual disease following large loop excision of the transformation zone(LLETZ) surgery may be missed in screening when cytology is used.In a 2002 review of 90 women, cytology had a positive predictivevalue of 81.3% and a negative predictive value of 55.4%.Results from RWH comparing cytology and colposcopy for detectingSIL post-operatively suggest that cytology is more specific thancolposcopy (82.6% versus 24.4%), but far less sensitive(46.0% versus 90.5%).As cytology and colposcopy both present difficulties insensitivity and specificity, HPV testing may provide analternative approach. A review of 11 studies published from 1992to 2002 demonstrated that among 900 women treated for CIN, 204 hadresidual or recurrent cellular abnormalities and incidence of HPVwas 83%; among 696 women with apparently successful outcomes,the incidence of HPV DNA was only 15% .A meta-analysis of 11 studies suggests that the combination of HPVtesting with cytology is promising for post-treatment evaluation.A study currently underway at RWH aims to determine whether HPVDNA (HPV HC II test) is a marker for recurrent disease followingsurgical management of CIN. Since 2001, over 1500 women have beenrecruited at the time of surgical treatment for CIN. Overall,64% of the women had high-risk HPV detected at surgery. Forwomen with HSIL confirmed histologically at surgery, 79% hadhigh-risk HPV DNA detected on the hybrid capture test.These women are reviewed regularly and at each visit Pap and HC IItests are undertaken and colposcopy performed.The overall positive rate for high-risk HPV DNA fell from 31%at 3–9 months to 20% by 21–25 months post-treatment. If Papcytology and HC II were negative 12 months after treatment, only0.6% of women had HSIL.This study is still ongoing, although these preliminary resultssuggest that the negative predictive value of high-risk HPV DNAholds promise as a marker for the adequacy of HSIL treatment whenperformed ≥ 12 months post-surgery.Revised guidelines for post-treatment assessment of cervicallesions will be introduced in Australia in July 2006. Colposcopyand cytology should be undertaken 4–6 months after treatment forHSIL. Cervical cytology and HPV typing will be used at 12 months,then annually until negative results for both tests are obtainedon 2 consecutive occasions. From that time on, Pap smears willthen be at the recommended screening interval of 2 yearly.In Singapore, cancer causes more deaths than heart disease. CervicaCurrent cervical screening recommendations in Singapore recommendPap smears every 3 years for women from time of first intercourseor from 25 years of age until 65 years. A cervical screeningprogramme for Singapore was first proposed in 1992; however,breast screening was given priority. In 1997, a plan for a pilotstudy was submitted and accepted by the Health Promotion Board.Following 5 years of development, the pilot programme is currentlyunderway. Roll-out nationally had begun in 2004.ensure coverage across the population, through education ofdoctors and womenprepare laboratories and standardise reporting—a localsystematic reporting system has been adopted,effectively manage and treat women with abnormal smears,address the issue of false-negative Pap smear results.Past failures of cervical screening ..39].Sasieni et al used UK data to compare the incidence of cervicalcancer in different age groups of women against the number ofyears since their last negative screening result . His finThe proportion of women in the community who are screened at therecommended frequency will also influence any evaluation. In 2004,around four in every five British women aged 25–64 years had beenscreened for cervical cancer within the previous 5 years.Primary care practices carry the prime responsibility for thecontinuity of testing. A review of primary care organisations in2004 showed that coverage of eligible women in different practicesvaried from 70% to 90%.Training and evaluation programmes in cytology and colposcopy havebeen established. The majority of British laboratories reviewed in2003–2004 achieved 65–85% positive predictive values in theirreviews of cervical smears (the proportion of high-grade cytologyassociated with underlying high grade CIN).National computerised colposcopy data is not routinely collected;for example in 2003–2004, more than 70% of women with abnormalscreening results saw a specialist for colposcopy within 8 weeks.This was followed by a diagnostic biopsy in 40% of cases, and19% had lesions excised on that first visit. In 37% ofreferred patients, colposcopy appeared normal and no procedure wasrequired.New options such as HPV DNA testing, the availability ofliquid-based cytology and a growing awareness of the relativelysmall benefits gained through frequent testing for women < 40years of age, are likely to influence the evolution of the Britishscreening programme.In the Philippines, cervical cancer is the second most commoncancer among women, behind breast cancer . The ageThere is a close link between neoplastic cervical changes and HPVpersistence. Of 356 cases of SCC or ADC, 93.5% testedpositive for HPV, compared with only 9.1% among a controlgroup . HPV typAs two in every three cases of cervical cancer are detected inlate stages of the disease, the median survival rate afterdiagnosis is only 76 months; 5-year survival is 51.7%.The Philippine health infrastructure is not sufficiently developedto support a well-structured, cytology-based screening programme.Pap smears are available through family planning clinics andrelevant societies; however, screening is not coordinated orappropriately targeted. Alternative strategies for lowering thecervical cancer disease burden must be considered.The Department of Health and the Medical Faculty at the Universityof the Philippines reviewed screening options to identify anapproach that is feasible, cost-effective, and replicable, toreduce the need for extensive cytology services and radical formsof treatment.knowledge, attitude, practice, and behavioural modification,validity and reliability standards for the screening test,cost-effectiveness,health policy implications.Four approaches to screening were compared:unaided acetic acid visualisation (AA),magnified acetic acid visualisation (MAA),Pap smear using spatula (S),Pap smear using cervical brush (CB).Women 25–65 years of age were recruited for the study and ofthose screened and interviewed, 13 105 underwent colposcopy andwere included in the data analysis.The study focused onThe results demonstrated the potential for acetic acidvisualisation in a screening process .the acetic acid aided visual method be used as the initialscreen for cervical epithelial abnormalities at health centreswhere Pap smear is not available,all women showing abnormalities be referred for colposcopy,and biopsy, if necessary.Screening coverage for Filipino women is still low due toinadequate healthcare personnel and a shortage of facilities.There has been no sustained public health campaign topromote the benefits of regular screening. With many otherpressing public health priorities in the Philippines, funding forcervical screening is limited.As a result of this trial, the study group recommended thatCervical cancer is the most common neoplasm in Indian women, with126 000 new cases and 70 000 deaths each year. Incidence ishigher than in Eastern Asia ..48].In a 2005 survey of HPV genotypes at the AIIMS in New Delhi, HPV16 was by far the most prevalent type, detected in more than35%, while HPV 18 prevalence was ∼3%.The National Cancer Control Program has operated since1972. Although cervical cancer is a stated priority, there hasbeen no coordinated cytology screening.The current recommendation of the Indian Council of MedicalResearch is that all women should have a single Pap smear atapproximately 35 years of age. In reality, screening isopportunistic, frequently in research settings.Developing countries must rely on less sophisticated resources,such as visual inspection with acetic acid (VIA), visualinspection with acetic acid magnification (VIAM), or visualinspection with Lugol's iodine (VILI).A series of trials has evaluated the efficacy of these approachesin detecting high-grade disease. Results have been very variable,with VIA having a sensitivity of 55 –88% 50,,50, 51 asimple, easy-to-learn approach,low startup and ongoing costs,less reliance on infrastructure or medicalspecialists to perform procedure,immediacy of results,potential for integration into primary health care services.In screening for cervical cancer, VIA offers the followingadvantages over alternatives:moderate specificity—resulting in higher referraland potential over-treatment,dependence on the person doing the evaluation—needfor standard training methods and quality assurance,lower accuracy in postmenopausal women.These need to be weighed against the disadvantages:In detecting high-grade cervical lesions, the role of HPV testingremains unclear. The test could be undertaken usingsamples collected by the patient. In a recent trial byAIIMS, 93.5% of participants provided a satisfactoryself-sample, and concordance between physician-collected andself-samples was high (93.8%).HPV testing can be automated and provides a standardised,objective result. In combination, it can improve the sensitivityof Pap smears and VIA.However, major problems for the widespread adoption of HPV testingin India are its cost, the need for sophisticated laboratoryinfrastructure, and repeat visits.Newer technologies may increase the specificity of testing withoutloss of sensitivity, but are currently too costly for generalisedadoption.Point-of-care diagnostic tests such as VIA and the “rapid” HPVtest will benefit populations with poor compliance.Mortality data from the 1970s to the 1990s suggest that Chinasuffers relatively high cervical cancer mortality, particularly inthe rural mid-west. Wudu in Gansu province and Yangcheng in Shanxihad age-adjusted mortality rates of > 40/100 000 in 1990–1992.Better diagnosis and treatment have reduced deaths from cervicalcancer, but the improvement is not uniform and mortality rates areunchanged in some counties.There are no national screening programmes for cancer in China. Inthe case of cervical cancer, limitations include the nationwideshortage of cytologists.In late 2003, a national cancer prevention and control strategywas finalised and endorsed by the Ministry of Health, followingconsensus meetings for early detection and treatment across ninecancer types.Two demonstration centres for cervical cancer prevention andcontrol have been established in Shenzhen (South-East China) forhigh resources settings and Xiangyuan (North-West China) for lowresources settings . A goverThe first Shanxi Province Cervical Cancer Screening Study (SPOCCSI) included 1997 women who underwent a cervical evaluation usingHPV self-test, optical biopsy, liquid-based cytology (ThinPrep),VIA, direct testing for HPV, or colposcopy with biopsy .n = 3252) underwent colposcopy andbiopsy. Women with CIN 2+ lesions were treated; those with CIN 1lesions will be followed up in 12 months.A second study (SPOCCS II) included > 8000 women who submitted aself-sample for HPV at their village and subsequently visited theclinic for HPV Direct Test, LBC (AutoCyte), and VIA . Those wIn both studies, women with cervical cancer or CIN 2+ lesions onbiopsy were likely to be infected with HPV (> 95%). Even forwomen with CIN 1 lesions, the attributable risk of HPV is as highas 95%. The incidence of HPV among women with normal biopsieswas < 15%.Persistent HPV infection was higher among women aged 50–54 yearsthan younger women in Shanxi, but there were marked differences inthe age-related curves for women in rural areas versus cities.Extensive lifestyle data were collected covering sexual history,child bearing, occupation, health, bathing practices, age atmenarche and menopause, education, and income.Lifestyle had a significant effect on HPV and cervical cancerprevalence in Shanxi. Risk factors that appeared to contribute tothe likelihood of cervical cancer were subject promiscuity (OR= 1.42); husband's promiscuity (1.42); bathing at a publichouse (1.23); postmenopause (1.22); and current smoking(1.17). Surprisingly, education appeared to slightly raise thelikelihood of HPV.When self-testing was compared with direct testing for HPV,specificity for CIN 2+ was identical (85.9%), whilesensitivity was higher on direct testing (97.6%) than forself-testing (83.5%).In both trials, each screening test was compared with pathology todetermine accuracy in detecting moderate-high-grade lesions .With high sensitivity (> 96%) and moderate specificity(86%), the HPV direct test could be used as a primary screeningtest for cervical cancer risk. Self-sampling is simple and lessexpensive; however, improvements in instructional leaflets will beneeded.Combined HPV and VIA offers potential for screening in themid-west regions of China, but for consistent results, VIAtraining will be essential.Hong Kong has a population of 6.8 million. Life expectancy for women at birth was estimated to be 84.3 years in 2003.During the period 1988–1992, Hong Kong's ASR for cervical cancer was ∼17; this is lower than that of the Thai, Korean, Filipino, and Singaporean-Chinese populations, but higher than in Japan  59]..59].Until 2004, there was no centrally organised, systematic cervicalscreening programme (CSP) in Hong Kong. Screening was generallyopportunistic or included as part of a general checkup. Screeningpractices varied between different healthcare providers and therewas little collaboration between public and private sectorhealthcare.Approximately 45% of women, primarily those who were educatedand health-conscious, were being screened. This somewhat randomcoverage was not equitable or efficient, and was unlikely to becost-effective.Despite this, the ASR for cervical cancer declined steadilybetween 1983 and 2000, the most significant fall being among women50–65 years of age. About 50% of cases are diagnosed at stage1.First approved in 2001, the Hong Kong CSP was launched in March2004. The goal is to reduce the incidence of, and mortality from,cervical cancer by facilitating regular screening for all patientsat risk.raise public awareness,improve population coverage,promote more equitable and efficient screening,build quality assurance into the services throughprofessional education and clear guidelines,support private sector activity.Following statistical modelling, the target population was set toinclude all women 25–64 years of age who have had sex. After twoclear annual checks, screening will be scheduled every 3 years,and discontinued at 65 years if the previous Pap smears arenormal.Stated objectives are toUsing triennial screens, it was estimated that if coverage raisedto 80% of the population, there would be ∼75%decrease in the number of cases of cervical cancer.It is hoped that the CSP will increase coverage from 43% to60% within 3 years, and to 80–85% in the long term.During the period March 2004–June 2005, almost 150 000 womenwere enrolled in the CSP. Based on age quintiles, enrolment has beenhighest among women 40–44 years of age. There are large variationsbetween districts.http://www.csis.gov.hk) accommodating the input of data online.The CSP incorporates a centralised information system with awebsite has developed guidelines for the taking of Pap smears andmanagement of abnormal smears . Other rCervical cytology laboratories operating under the CSP must beapproved by international bodies and the Hong Kong laboratoryaccreditation scheme.The CSP uses Pap smear cytology as the primary screen.Among smears undertaken to date, 5.6% have shown epithelialcell abnormalities. Of the abnormal smears, 60–80% wererecorded as ASCUS. ASCUS patients were either referred forcolposcopy or followed up with a further screen. However, only2–10% of ASCUS patients have serious disease .HPV testing is currently under consideration as a means oftriaging patients with ASCUS and low-grade lesions.n =5579); on second review, 9.8% and 1.7% showed LSIL andHSIL lesions, respectively ..98].Recognising some of the problems associated with cervical cancerscreening in Japan, the Anticancer Committee of the JapanAssociation of Obstetrics and Gynecologists appealed for revisedlegislation. It was proposed that eligibility for screening beextended in an effort to detect cervical cancer earlier, avoidhysterectomies, and allow women to conceive. Legislation wasrevised in 2005 to initiate biennial screening for women from 20years of age and to improve education regarding HPV.An internet survey of 2000 randomly selected Japanese women(20–59 years of age) was undertaken in April 2005. This wasdesigned to evaluate knowledge of cervical cancer, motivation forparticipation in screening, and knowledge of papillomavirus andtests for HPV.Over 1000 (51.9%) questionnaires were available for analysis.More than half the women surveyed said they knew about cervicalcancer and the methods of cervical cancer screening. A similarnumber (51.3%) were aware that the incidence of cervicalcancer had increased in Japan in recent years, yet almost 60%were unaware that the disease was not terminal when detected earlyand treated.The most frequently mentioned sources of information wereTV/radio, books, and the Internet. Although 49% of respondentssaid they had been tested for cervical cancer, only 18% werescreened annually.Among women who were not screened, the most common reasons citedwere the troublesome nature, cost or shame of the procedure, andinadequate time. Very few women (13%) were aware of HPV or itsmeans of infection.However, at least three in five (61%) said they would bewilling to undertake an HPV test.One hundred and twenty-six respondents made suggestions as to howscreening could be improved. Their demands were mainly for moreinformation and/or funding from the government to reduce the costof the tests. Some expressed the desire for greater protection ofprivacy  and for screening tobe easier.There is clearly inadequate education and understanding ofcervical cancer within the community. Furthermore, there ispresently no clear quality direction for the screeningprogramme—Pap testing is not liquid-based, is not classified bythe Bethesda system, or backed up with an HPV DNA test. There areno guidelines for SIL management.Recommendations to improve the system include extending annualscreening to women < 30 years of age, with biennial screeningfor women > 30 years following three consecutive negative tests,or including HPV DNA testing in a triennial screen .Regardless of the method, more education on cervical cancer,screening, and HPV is needed.The Philippines is an archipelago of 7167 islands, with apopulation of more than 87 million people. It is a young nation byage—only 4% of the population are > 65 years of age.Poverty is widespread, and communication and transport aredifficult, particularly in rural areas.Pap smears cost P400 (US$7). The minimum daily wage is US$3.57and the average family income is US$221/month. Preventativehealth is a luxury.Twenty million women are aged 25–55, the target population forcervical cancer screening. Twenty-three percent of women haveexperienced sexual activity by age of 24, including 1.2%before age of 13.Cervical cancer is the Philippines' fourth most prevalent cancer,behind lung, breast, and liver tumours.In a single year, there are over 4500 new cases of cervicalcancer. Most (93.5%) are linked to HPV 16 or 18, and are notdetected until they have become invasive. The incidence is likelyto be underestimated—systematic data gathering is poor,particularly in rural areas where the majority of the population(62%) lives. Coverage by the Cancer Registry is only 25%.There is no organised and sustained cervical cancer controlprogramme, and only 12% of the population are screened.Responsibility for such a programme was recently moved from theDepartment of Health (DOH) to Local Government Units.Unfortunately, these units are overloaded with patients andmultitasking reduces their effectiveness.Knowledge about cancer, and particularly cervical cancer, is poor,due to the lack of readily available responsible publicinformation and trained medical personnel.barangay (public) health workers.Among the 3600 general practitioner graduates from 39 medicalschools each year, 68% leave for overseas, as do 50% ofnursing graduates. Those who do not migrate practice in urbanareas, leaving rural areas under the care of inadequately trainedhealth workers. Education regarding cervical screening must extendbeyond doctors to include cytotechnologists, gynaecological andoncology nurses, and midwives. In many areas, screeningcurrently relies on A range of options are under consideration to improve populationscreening for cervical cancer. Before systems can be expandeddramatically and a public information campaign is initiated,diagnostic and therapeutic facilities must be able to cope withincreased demand.The Cervical Cancer Research Project has been planned as acooperative venture between local, national, and internationalorganisations. In 2002, a pilot programme began in Cebu province,which is now being used as a training centre for implementation inother provinces. The DOH mandated the implementation of animproved national screening programme in 2005.A training manual has been developed and guidelines prepared forsetting up clinics. The plan includes a directory of key contactsand a registry of the target population.When diagnostic and therapeutic centres are in place andsustainable, there will be a media campaign to educate women, withongoing health education to maintain their interest. Advocacymeetings among medical, diagnostic, more general interest groupsand support groups, are planned. Solutions have been identifiedfor resource and programme sustainability problems.Simple and less expensive methods of cervical screening based onvisual examination of the uterine cervix are currently beinginvestigated as alternatives in low-resource settings. VIA hasbeen widely evaluated for accuracy in detecting CIN 2/3 lesions inresearch settings in low-resource countries. Suspicious CINlesions are characterised by well-defined acetowhite areas in thetransformation zone surrounding the cervical os, in closeproximity with the squamo-columnar junction, or by acetowhitelesions occupying the entire cervix. The immediate availability oftest results following VIA facilitates the diagnosis and treatmentof lesions in the same session, which has important logisticaladvantages and ensures a high participation.A series of reports on the use of VIA in South Africa–103, Zimn = 48 225) and to a control group (n = 30 167),which received health education and existing care [The efficacy of a once in a life-time VIA screening in reducingincidence of and mortality from cervical cancer is being assessedin two cluster RTCs in India. In one, women aged 30–59 years inDindigul district, South India, were randomised to VIA screeningby nurses  . Of the Studies indicate that women are willing to participate in andaccept VIA screening, and detection rates of early lesions usingvisual testing attest to its validity and usefulness. Goodtraining is needed to achieve fairly accurate and moderatelyreproducible results with visual tests in developing countries. Awide range of health care providers including trained medical andnonmedical personnel can provide VIA after roughly 5–10 days ofcompetency-based training.Quality assurance of visual screening in field conditions poses amajor challenge. Close monitoring of test positivity and diseasedetection rates as well as periodic retraining are essential tomaintain good standards of visual testing. While a resultantreduction in the incidence and mortality associated with cervicalcancer following VIA screening has not yet been proven, this iscurrently being addressed in randomised screening trials.A nationwide cancer prevention programme using annual Pap smearshas dramatically reduced cervical cancer incidence and resultantmortality in Japan. However, the Pap test is not always accurate,and false-negative results can have serious implications. This hasled to a reevaluation of the cancer screening programme in Japan.A recent study evaluated a combination of Pap smear and HPV DNAtesting for routine cervical cancer screening. The focus was onIshikawa prefecture, in the northwest of Japan's main island.Kanazawa is the capital of this prefecture, which has a populationof 1.2 million.More than 8000 women were recruited into the study between October2003 and April 2004. Two cytology samples were taken from theectocervix using a cytobrush, one for Pap smear and the other forHPV DNA test. HC II for high-risk types of papillomaviruses wasused, and positive samples were classified further using theDNA-chip method.Cytological diagnosis was according to the classification systemestablished by the Japanese Society for Obstetrics and Gynecology(JSOG). This differs from the Bethesda system in classificationterminology, but classifications IIIa, IIIb, IV, and V wouldequate to the ASCUS, LSIL, HSIL, and invasive cancer categories.Colposcopy and biopsy were recommended in all cases cataloguedabove JSOG II.HPV was detected in 7% of women with normal cytology. Overallincidence of HPV infection was 11%. It was more common foryounger women to test positive for HPV than older women, with45% of women aged 15–19 years testing positive. More than 1500women in their 20s were tested—24% were positive forhigh-risk HPV. In women > 40 years of age, levels of infectionfell to 4–7%.There was a higher incidence of Class IIIa cytology among HPV+women (74%) than among HPV− women (41%). Among 26 womenwhose cytology was normal, but who had CIN lesions on histology,23 (88%) tested HPV+. Among 57 women with abnormal cytology,86% had CIN lesions and 92% were HPV+. This demonstratedthe potential for HPV testing to detect women graded normal withroutine cytological screening, despite serious lesions (CIN3 orinvasive cancer).Those samples that were positive with hybrid capture assay werefurther examined using Biomed-Lab DNA-Chip. The most frequentlydetected type of HPV in these Japanese women was HPV 52, followedby HPV 16.Almost half the samples were infected with more than a single HPVtype. Multiple infection was more common among younger women,particularly those in their late teens.It was more common to find multiple infections in women with CINlesions than in women with invasive cancer.In 2004, as a result of these findings, Japan introduced a newapproach to screening for cervical cancer. Samples withquestionable cytology (ASCUS using the Bethesda classificationsystem) are routinely examined for HPV DNA. HPV+ women are thenrecalled for colposcopy.As in this sample from Kanazawa city, it is clear that the use ofHPV testing has improved the positive predictive value of cervicalcancer screening. Among 400 samples that revealed questionablecytology, 50 cases were HPV+ on testing, so an additional 42women were referred to colposcopy. This detected an additionalfour cases of CIN2 lesions and two of CIN3 lesions. These sixwomen were treated surgically—earlier than if the HPV test hadnot been used.In conclusion, the combination of Pap cytology and HPV tests hasimproved cancer screening efficacy.The HPV DNA test incurs additional costs. However, for women whoare negative on cytology and HPV, the inter-screening intervalcould be extended, thereby recouping the cost.Data from 1996 showed that cervical cancer was the most commoncancer in Thailand women, with an ASR of 19.5, higher than thatfor breast cancer (ASR ∼ 17.2) .Within Thailand, incidence varies between regions, with Chiang Mai(ASR 25.6) and Lampang (23.6) having higher than nationallevels. The age prevalence is fairly consistent between regions,peaking at 45–55 years of age.Unlike more economically developed countries, where most cervicalcarcinomas are detected early, only one in five Thai cancers willbe detected in Stage 1 .In 2005, the cervical cancer incidence was 19.5/100 000 women.This equates to 30 000 cases of invasive cancer over a 5-yearperiod. Five women die from cervical cancer every day in Thailand,and 10 new cases are detected daily.Thailand has limited resources for screening. In 2004, acytology-based programme was established, which recommendedscreening every 5 years and aimed to achieve 50% coverage. Thescreens were most commonly undertaken at family planning clinics.By 2005, the programme was demonstrating coverage rates of only10–15%. The lack of cytoscreeners and pathologists led to longdelays in receiving test results, and no firm policy had beenestablished to assist healthcare professionals to deal withabnormal results.An intensive and thorough training programme has now begun tobuild competency in VIA and cryotherapy.Clinics are encouraged to rely on VIA if Pap smears are notperformed efficiently. Ten of the 75 Thai provinceshave adopted this approach. Women 30–45 years of age areencouraged to be screened every 5 years. The objective is toachieve 80% coverage over 5 years.In Roi Et Province, a concerted effort has been made to deliverthe screening service to women. Mobile units visit rural healthcentres. With these intensive mobile units, district teams areable to test three times as many women in a week as services atdistrict hospitals. This success has demonstrated theeffectiveness of taking the service to the women, rather thanrelying on women to attend screening at a distant location.Health centres staffed by 3–5 persons are at the core ofThailand's primary care system. They generally provideapproximately 5000 residents from 8–12 villages with basicmedical care and health prevention and promotion programmes.Involvement of the health centre staff in cervical cancerprevention activities is essential. They identify the targetpopulation by visiting all community households and build aregistry of names of women in the 30–45-year target age group, totrack their attendance at clinics.The community health centre takes responsibility for organising,promoting, and coordinating designated cervical screening days.Staff will inform the local population about the VIA test usingloudspeakers, letters, and presentations. Health volunteers ineach village also contact women directly.This programme has proved being more reliable and efficient thanany other, and is being expanded to additional districts andprovinces.Since 1980, Korea has had a national tracking system for majorcancers, which includes site-specific and regional tracking. Thedatabase for national cancer incidence is estimated to be 95%complete.Cervical cancer is the fourth most common cancer in Korean women.With an AAR of 15.5 in 2001, it is less common than cancers ofthe stomach, breast, and colon/rectum.Between 1993 and 2001, the curves for age-specific incidence ofuterine cancer fell, with this trend most marked among women50–70 years of age .Almost 40% of malignant cervical cases are being detected insitu, before they become invasive. For women diagnosed withcervical cancer during the period 1995–2001, 6.6% diedwithin 12 months. Almost 80% survived for at least 5 years.There are local variations in the incidence and mortality ofcervical cancer. Morphologically, the majority of tumours(∼ 80%) are of squamous cell origin; however, duringthe 10 years from 1993, there was a growing proportion ofadenocarcinomas . The5-year survival rate for adenocarcinomas (74.3%) is less thanthat for SCC (81.4%).no family history,no/few children,marriage,late first sex,circumcision.In a review of HPV types in Busan for the IARC HPV InternationalPrevalence Survey, the seropositivity of antibodies to HR-HPV was 19.8% among sexuallyactive women 20–74 years of age. The most common types were HPV70, HPV 33, and HPV 16 [Key factors associated with a lower risk of cervical cancer inKorean women are no famild HPV 16 . All sevThis trial was undertaken by the Korea National Cancer Center withthe Unit of Field and Intervention Studies in the InternationalAgency for Research on Cancer, in 2002, to determine at what agewomen become sexually active, exposed to HPV-DNA, and thenseropositive for HPV 16 and HPV 18. It also provided anopportunity to assess willingness to participate in future HPVvaccine trials.Students 16–26 years of age attended a health education class andwere asked to complete a survey. They provided a blood sample andeither a vaginal (self-collected) or penile (physician-collected)swab.Among 672 females, 15.2% tested positive to HPV, 9.4% ofwhom tested positive to a high-risk type. Among this latter group,there was a high frequency of infection with multiple strains.Among males 8.7% tested positive for HPV . The risAmong this group of 1100 university students, 64% of men and58% of women said they would be willing to participate in atrial for HPV vaccines.Since 1988, medical insurance beneficiaries have received a Papsmear for cervical cancer check as part of their general healthcheckup. In 1999, the National Screening Program began coveringMedicaid patients' screens for stomach, breast, and cervicalcancers. Since this time, coverage has been expanded and about50% of insured patients are currently included.The current recommendation is that all women > 30 years of ageshould have a Pap smear every 2 years. Participation in cervicalscreening in 2002 was 15.6% and 10.8% in 2003.Incorporation of HPV testing into the screening process mayimprove sensitivity and allow the screening interval for manywomen to be extended.In 1988–1992, the AAR of cervical cancer in Taiwan(22.2/100 000) was higher compared with other Asian nationswith Chinese populations, such as Singapore (16.3/100 000) andHong Kong (15.3/100 000).In 1995, Taiwan instituted the National Cervical Screening Programfor women aged > 30 years.As part of the programme, extensive and ongoing training has beenintroduced for cytotechnicians, nurses who collect samples, andgynaecologists undertaking colposcopy. To participate in theprogramme, laboratories and their staff must be accredited and arereviewed regularly.Every year since 2000, more than 50% of eligible women hadparticipated in cervical screening within the previous 3 years.From 9.2% of eligible Taiwanese women screened in 1995,screening levels rose annually until 2001, when 30.1% ofwomen undertook a screening test; 27.1% of Taiwanese womenwere screened in 2003.When the programme began, cervical cancer levels appeared to risefrom 30–35/100 000 in 1995 to over 50 in 2000. This probablyreflected more frequent diagnosis due to increased screeninglevels, rather than greater incidence. Furthermore, the AAIRpeaked in 1999 and declined in the next 2 years. During the sametime period, the proportion of cancers that were detected in siturelative to invasive cancers rose dramatically, reflecting earlierdiagnosis of the condition.n = 48), theincidence of HPV infection was 92%. HPV strains 52 and 58 werethe most commonly detected.In 1992, a nationwide survey of more than 13 000 women wasundertaken across seven counties and reported by Liawet al . This deHsu et al reported the results of a population screen for HPVvirus using MY09/11 PCR and sequencing . Among wThe link between infection with HPV and the development ofcervical cancer is also reflected in other results. Patients whoshowed SIL on Pap test were eligible for the study; 1284 womenwere recruited. Infection with HPV was confirmed using HCII andPCR-Strip testing. Among those with low-grade lesions, theincidence of HPV infection was 75%. Those with high-gradelesions had an HPV incidence of 83.6%. All (100%) 16 womenwith invasive carcinoma tested positive for HPV.Further research has evaluated the relative risk of cervicalcancer for different strains of HPV. More than half of women(51%) with cervical SCC tested positive for HPV 16, while HPVs18, 58, and 33 were also frequently detected. In cervicaladenocarcinoma or adenosquamous carcinomas, HPV 18 was detectedin 58.8% and HPV 16 in 35.3% of affected women. Among263 cases of cervical cancer in Taiwan, the majority were linkedto five strains of HPV: 16 (50.7%); 18 (11.9%); 58(10.1%); 33 (8.4%) and 52 (3.1%).n = 436). Strains of HPV most frequently associatedwith ASCUS and AGUS cytology were 52 (18%), 16 (15%), and 58(15%).ASCUS and AGUS abnormalities detected cytologically, andfrequently associated with venereal warts, were also evaluated forHPV status , 16 (11.7%), and 58 (11.2%).Low-risk types were detected in 18.4% of cases.Compared with other countries, Taiwan has a disproportionatelyhigh incidence of HPVs 52 and 58. This dramatically contrasts withEurope, where HPV 16 is the predominant strain.Phylogenetic trees show that differences in the origins of HPVs 58and 52 can be traced in Asian nations such as Thailand, Hong Kong,and Taiwan.Pilot studies are now underway to investigate the mostcost-effective way to include routine HPV testing in Taiwan'scervical screening programme. A self-screening test usingmenstruation pads is among the options being investigated.Due to the extensive recording undertaken for the screeningprogramme, Taiwan has data to conduct simulation modelling, whichcan aid planning decisions. The country has also been involved intrials for HPV vaccines currently in development. In theshort-term, decisions will be made regarding frequency of testing(possibly extended to 5 years) and the timing of HPV testingrelative to smears and cytology.Taiwan has already experienced success with a vaccination toprevent cancer. Following the launch of mass vaccination againsthepatitis B, incidence of hepatocellular carcinoma droppedsignificantly.As the majority of cervical cancers can be linked to infectionwith a few high-risk strains of HPV, vaccination offerssignificant potential to reduce the incidence of cervical cancerin Taiwan.Emerging evidence has changed the way low-grade cytologicalchanges are viewed, but it has not clarified patient management.Members of the Ontario Cervical Screening Program reviewed theavailable evidence in order to optimise national guidelines.The interdisciplinary guideline committee defined a series ofquestions regarding the cervical screening process, with the aimof defining the optimal management for women with abnormalcytology .The Appraisal of Guidelines, Research, and Education (AGREE)process was chosen as the framework for reviewing the guidelines.AGREE consists of 23 Likert-scale items organised into sixdomains, and offers confidence that potential biases in guidelinedevelopment have been addressed.http://www.guideline.gov andhttp://www.g-i-n.net), systematic review websites , and references cited on other materials.The guideline search and retrieval included some online databases,known guideline developer websites ,2001 , and NatEach source was subsequently evaluated by the panel according toAGREE classifications covering quality, currency, and content.The two existing guidelines were subjected to detailed review,which considered their scope, stakeholders, rigour, clarity,applicability, and editorial independence.Every recommendation within the guidelines was reviewed accordingto the level of evidence on which it had been based. Two differentranking systems were used in this process .Low-grade lesions present a dilemma when detected duringscreening. Half of the women with LSIL cytology will be normal ifchecked subsequently after 4–6 months, yet the remainder willprogress to HSIL or invasive cancer within 2 years .no action, but repeat cytology in 4–6 months,immediate colposcopy,HPV testing.The ASCUS/LSIL Triage Study (ALTS) Group evaluated 5000 women todetermine how best to manage these early, inconclusive lesions.They found that HPV testing was likely to be positive and wouldnot clarify management.Three management approaches could be taken for these patients:The ASCCP Guidelines, based on Level CIII evidence, permitmultiple paths following LSIL cytology, with differentrecommendations for teens and postmenopausal women.Moscicki suggested further revisions to approaches foradolescents. He believed that LSIL reflected an HPV infection, andcommented that “most guidelines in the USA were overaggressive intheir management of abnormal cytology in adolescents and youngwomen (resulting in) costly over-treatment” . The medThe NHMRC based their 2004 recommendations on Level CII evidence.If a woman is > 30 years of age and has not experienced negativecytology in the previous 2-3 years, she should have immediatecolposcopy or repeat cytology after 6 months. If the woman is onbiennial surveillance or < 30 years of age with no cervicalcytology history, repeat cytology screening in 12 months. A womanshould be referred for colposcopy following two abnormal tests; ifthe second test is normal, it should be repeated after 12 months.The guideline panel then needed to decide which guideline/s wouldbest meet Canada's needs and goals.The Program in Evidence-Based Medicine recommended that women withLSIL on Pap smear should be sent for colposcopy or repeatcytology after 6 months (B-II). All women whose cytology isabnormal on the second test should be referred for colposcopy. Ifthe second Pap test is normal, it should be repeated again after afurther 6 months and the woman referred if the result is ASCUS orabnormal (C-III).Surveys were completed by 180 physicians to review the guidelineproposal. Approximately half agreed that patient outcomes would beimproved by the proposed changes. However, there was universalagreement that referring all LSIL cases for colposcopy would beimpractical.After deciding which people and organisations should endorse thedocument, plans were made to launch the revised guidelines inSeptember 2005. Following publication, the document will bereviewed annually.Evidence was reviewed to assess different management approachesfor women who have low-grade neoplasia on biopsy (CIN1). Availableevidence did not suggest whether it would be better to followupthe finding at a later date or to treat the lesion immediately.Treatment decisions were based on histological results. However,there was huge variability in how operators coded their findings.False-positives and uncertainty lead to unnecessaryinvestigations, possible over-treatment, anxiety, and increasedcost.A number of investigative immunochemistry techniques offer newinsights and potentially more objective foundations for clinicalmanagement.Among the most promising is p16(INK)4a, a protein marker that isonly present in cases of cancer, CIN 2/3, and CIN1 lesionsassociated with HR-HPV , 131.n = 194) were reviewed by fivepathologists and coded [As part of a randomised trial in the best management strategy forbiopsy proven CIN1, cone biopsies (nd coded . AlthougA study was undertaken to determine whether p16(INK)4a or otheradjuvant techniques might enhance the evaluation of CIN1 (LSIL)lesions . FollowiHistopathologic diagnosis was most confused when rating a sampleas either CIN1 or normal/reactive. The inconclusive samples weremore frequently positive for HPV than for p16(INK)4a.However, 23% of benign cases were also positive for p16(INK)4a,and half of these were positive for HPV. Ongoing monitoring willreveal the role of p16(INK)4a in these patients' disease courses.A substantial number of CIN1 patients were negative forp16(INK)4a. Whether p16(INK)4a-positivity has significance interms of natural history requires ongoing followup of thesecases.Approaches to treatment for HSIL depend upon the type of histology, the size and accessibility of thelesion, the patient's stage of life and the surgical optionsavailable.If the whole lesion is not visualised as it involves theendocervical canal, a loop or cone biopsy should be taken. If itis in range, the lesion can be removed by loop, cone, or surgicalablation.If microinvasion or ESI are suspected, the margins on the biopsywill be important in guiding management. A cold knife is lesslikely to denature cells than a loop, and is therefore preferredfor reviewing margins.In the case of noninvasive HSIL, either procedure can be used.There is limited guidance on what endpoint determines a successfuloutcome. Rate of recurrence of CIN is perhaps the best measure toguide followup.A Cochrane review reported on 28 trials using different surgicaltechniques to manage CIN without identifying any “obviouslysuperior technique .”P = .006), but there was nodifference in likelihood of caesarean delivery, precipitouslabour, induction or neonatal intensive care admission [The LEEP approach has been linked to a number of obstetricdifficulties. A systemic review that factored in smoking,concluded that following LEEP, women were more likely to givebirth preterm .Rome and Brown were able to demonstrate the anticipated higherrisk of recurrence in patients with < 3 mm invasion whereLVSI was identified pathologically . RelativIf 1–3 mm invasion, treat as for ESI, unless LVS isseen. Consider hysterectomy in postmenopausal women and whenchildbearing is complete.When the invasive zone is 3–5 mm, a hysterectomy ispreferred; however, where fertility is an issue, a cone resectionincluding lymph nodes is an option.In cases where the margins of the biopsy are positive, and theinvasive depth ≤ 3 mm, the cone may be repeated andretested. If CIN is present at the ecto/endocervix, follow withcolposcopy/cytology and ECC.At the Royal Women's Hospital (RWH) in Melbourne, Australia,disease management recommendations for microinvasive lesions areas follows.AIS is a recognisable precursor to invasive cancer. It isfrequently multifocal and often associated with squamous lesions.The predictive value of cytology is 75%. Since the 1970s, theincidence of AIS (relative and absolute) has increased; HPV 18 andoral contraceptives have been implicated.Soutter et al reported retrospective outcomes for 53 women inEngland, whose AIS was treated with cone alone . Ten perThis classification includes glandular carcinomas such asendocervical, villoglandular, intestinal, endometroid, clear cell,and adenosquamous.Östör and Rome reported outcomes for 436 womenwith microinvasive adenocarcinoma defined as invasion≤ 5 mm, and associated with complete obliteration ofnormal endocervical crypts, extension beyond normal glandularfields, and stromal response . Of thesAnother report reviewed retrospective data and recommended that,where invasion was < 5 mm, the likelihood of lymph nodemetastasis and disease recurrence were very small, and thereforeconservative surgery could be considered with some confidence.Conisation is a good approach when lesions are < 3 mm.Lymphadenectomy is recommended whenever LVS is positive.Recone if there is any uncertainty.For lesions 3–5 mm, a simple hysterectomy is recommended.With the limited data available, the RWH makes the followingrecommendations.Adequate data are available to make recommendations for squamouslesions with confidence. It is likely that adenocarcinomas can bemanaged similarly, although more data are needed to providestatistical validation.condylomata acuminata) is one of the most common STIs worldwide, usually resulting from infection with HPVtypes 6 and 11 [Genital warts , butrecurrences are common (30–60%). Antiproliferative agents suchas podophyllotoxin or 5-FU will cause the warts to regress.There is no specific antiviral agent for HPV. However, the immunemodulator imiquimod, which has specific but broad antiviralactivities, has been an approved therapy specifically for genitalwarts and has been endorsed in US-CDC , Latin AImiquimod induces interferon-alpha in an early, nonspecific,innate immune response as well as stimulating CMI , 150.ItActivated dendritic cells engulf HPV from infected cells andprocess the viral antigens on their cell surface . TheyleStimulated by the presence of cytokines and chemokines, T-cellsand monocytes migrate toward the site of infection. The T-cellsinvade the wart and kill infected cells, which are thenphagocytosed.The wart gradually clears and immune memory is established. Thiscan reduce recurrences, as newly infected keratinocytes will berapidly killed.P < .0001). If the endpoint was > 50% wart reduction, overall success was 76% for imiquimod patients compared with 28% for placebo. Erythema at the wartsite occurred in two-thirds of patients using imiquimod cream,while smaller numbers experienced erosion (32%), excoriation(24%), oedema (16%), and scabbing (15%). Interestingly,erythema was reported by one in four who received the placebocream containing no active ingredient.A 1998 study reported the outcomes of an intent-to-treat RCT ofself-administered imiquimod cream in 311 patients with externalanogenital warts . The creAnother study sought to determine whether subgroup demographicsinfluenced treatment outcome . The conPatients around the world who had previously been treated usingcryotherapy or podophyllin rated imiquimod superior with regard toits convenience and lack of pain .A series of trials also demonstrated the efficacy of imiquimod asan adjunct to ablation  and high-grade(HSIL/cancer), colposcopy scored 85% for sensitivity and 69%for specificity.To confirm the efficacy of lesion ablation following colposcopywithout histological confirmation, Belinson et al team reviewed1997 women in rural China . Key facA number of published studies have compared colposcopy with othertechniques to evaluate its reliability in screening; conclusionsvary dramatically and are clearly influenced by study design–162.Reid and Scalzi developed a scoring system based on sharpness of alesion's margins alongside colour, vascularisation, and iodinestaining to rate colposcopic findings . CarrierPretorius et al recognised that the most likely reason forcolposcopists to overlook malignant lesions was their size. When a “Assuming colposcopists use the same definitions, reproducibilityof colposcopic assessment depends in part on colposcopists usingsimilar “thresholds of certainty” for categorization findings asto normal versus abnormality and grade.” (IARC 2005)Digital photographic databases can retain data for post-treatmentaudit and comparison between units.Education is key to quality colposcopy. Consistency, andconsequently quality, can only be maintained if practitioners aretaught via rigorous training programmes to adhere to guidelines,and are regularly accredited.travelled as part of their occupation,indulged in extramarital sex or multiple marriages,had cancer of the penis,had a previous wife who had cervical cancer,were uncircumcised.The discovery of HPV as a sexually transmitted carcinogen providedan explanatory context for these observations.Over the years, both social and medical researchers have foundstatistical links between observed behaviours and the incidence ofcervical cancer. As early as the 1850s, differences in incidencewere noted between prostitutes and virgins/nuns. During thefollowing century, risk factors for cervical cancer was related towomen whose husbandsSpain , Colombia(34.4), Brazil (37.7), Thailand (22.4), and the Philippines(21.6) were selected for the IARC case-control studies toevaluate the role of males in cervical cancer. Overall, 1921couples were recruited.The objective was to determine the relationship between men'ssexual behaviour and penile HPV, and subsequently, levels ofcervical HPV infection and cervical cancer in their partners.There were some key differences in the sexual life and behaviourpatterns in the countries chosen. Men from South America generallyhad more lifetime sexual partners than men from Thailand, Spain,and the Philippines.In addition, men from Brazil and particularly Colombia were morelikely than those from Spain, Thailand, and the Philippines to haveregular intercourse before they were 18 years of age.Men from Brazil and Colombia were far more likely to beHPV-positive in the distal urethra than men from Thailand, thePhilippines, and Spain. However, this did not necessarilycorrelate with HPV positivity in their women partners .The ASRs of cervical cancer within the different populationscorrelated closely with both the prevalence of penile HPV and withcervical HPV infections.The data clearly demonstrate that in countries with low prevalenceof HPV, such as Spain, the risk of cervical cancer in women isinfluenced by the partner's sexual proclivity . HoweverHIGH-RISK countries: HPV prevalence in young malesis very high and any given sexual contact conveys a high risk ofexposure. When risk of infection at any given episode ofintercourse is high, increasing the number of sexual partners doesnot greatly increase this already high risk of infection.LOW-RISK countries: HPV prevalence in males is low andonly sexual intercourse with high-risk males or a high number ofpartners for women conveys a high risk of HPV exposure.The interpretation that can be drawn is as follows.n= 847) than circumcised (n = 292). Uncircumcised men in thestudy were > 3 times more likely to be positive for penile HPV(19.6%) than circumcised men (5.5%) [In this study, it was more common for men to be uncircumcised (n (5.5%) . OverallIn future, public health will need to consider the role of themale in planning management programmes for cervical cancer. It isevident that the risks for both infection and cancer developmentare influenced not only by the types and frequency of HPV within apopulation, but also by sexual behaviour. Women who have theirfirst stable sexual relationship at a young age (< 20 years ofage) have a greater risk of cervical cancer.Societal factors play a major role in sexual relationships, and inthe case of cervical cancer strongly influence nationalepidemiology of HPV-associated disease.n = 82) regressionoccurred in 53% of those whose partners wore condoms, comparedwith 35% of those whose partners did not. Among those withcondom-wearing partners, 23% cleared the HPV infection,compared with only 4% of those whose partners did not wearcondoms.Condom use has been associated not only with lower penileinfection rates and regression of penile lesions, but also withCIN regression and clearance of cervical HPV . In a 2-abstinence/monogamy/low promiscuity,late sexual debut (particularly in women),avoiding high-risk partners,consistent use of condoms,male circumcision,vaccination against HPV.Males clearly play a role in HPV prevalence within populations.Cervical cancer rates in women would be aided by any of thefollowing:HIV infection is not uncommon in many Asian countries. At the endof 2003, Cambodia, Thailand, Myanmar, India, Nepal, and Papua NewGuinea had known prevalence levels > 0.5% . As patiA study of women in four US cities found that 60–70% ofHIV-positive women tested positive for HPV, making them 2.3times more likely to be infected than HIV-negative women. Theywere also 1.9 times more likely to be infected with multiple HPVstrains, and 1.6 times more likely to have a higher HPV viralload .Women with HIV were also more likely to have persistent infectionswith HPV; immunosuppression appears to play an important role inmodulating the natural history of HPV infections .Palefsky et al looked specifically at HR-HPV types in HIV-positivewomen, finding a prevalence of 20–34% with an OR of 5.1compared with HIV-negative women .Immunosuppression in HIV is monitored through the CD4 count. Alower T-cell count is closely related to likelihood of infectionwith HPV, including high-risk types, a high viral load, andpersistence of the infection –174.A number of studies have demonstrated that the prevalence ofcervical cellular abnormalities is significantly higher inHIV-positive women –179.Most cytological abnormalities are ASCUS and low-grade SIL, withhigh-grade lesions diagnosed in less than 10%.Again, risk of cervical disease is greater when HPV load is high and whenInfection with HIV increases the incidence of SIL, almostcertainly because HIV-positive women are more likely thanHIV-negative women to have persistent infections with HR-HPV. Aprospective study showed that one in five HIV-positive women withno evidence of cervical disease developed biopsy-confirmed SILswithin 3 years .Four studies , 182 havThree studies , 178 havBy maintaining CD4 levels, HAART may impact on the natural historyof cervical disease in HIV-positive women. However, results of studies are mixed. Women on HAART were found to be more likely to experience regression of HPV-linkeddisease in three studies , 184 whiWhen HIV-positive women are treated surgically for CIN, they aremore likely to experience recurrence of disease than HIV-negativewomen. Cited recurrence rates have ranged from 39% to 56%,regardless of CIN severity or the mode of treatment (excisionversus ablation). The prime factor influencing rates of recurrenceis the level of immunodeficiency. Recurrence is halved in women onHAART. The conclusion was that although surgery is highlyeffective for immunocompetent patients, it only preventsprogression to cancer in HIV-positive women . DiseaseCase reports of invasive cervical cancers in patients with AIDSled the CDC to include cervical cancer as an AIDS-defining illnessin 1993 , 189.The risk of ICC among HIV-positive women means that more frequenttesting is justified. In a prospective preventative study,six-monthly testing was undertaken in women with CIN1 lesions.These infrequently progressed in women with HIV, so observationappears safe, in the absence of other indications for treatment. In a SwWomen with HIV are more likely to experience VIN than HIV-negativewomen (4.67 versus 1.31/100 person years) . IncidenHIV-positive women are also at a higher risk for both invasive andin situ vulvar cancers (relative risk = 5.8 versus 3.9). Younger3) andcervical disease is also present [Anal HPV infection is frequent (76%) in HIV-positive women. Prevale present . A Europ present .Because the Pap test has a 10–25% false-negative rateirrespective of HIV status, LBC may provide higher sensitivitythan standard cytology. HPV testing may be undertaken at the timeof the swab, and should certainly be used to review ASCUS samples.In HIV-positive women, more frequent screening is recommended ifHPV infection is known, there has been a previous abnormal smear,if CD4 < 200, or following any surgical treatment for cervicallesions.Colposcopy should be used routinely in all HIV-positive women witha known HIV-positive status, if immunosuppressed (CD4 < 200) andfollowing an abnormal Pap smear . The entBecause colposcopy is a subjective science and prone tofalse-negatives and -positives, biopsies should be consideredearly on in the evolution of any abnormality.Anal Pap smears have not been adopted in the USA. High-resolutionanoscopy can be considered, and any abnormal areas sampled.Vulvo-vaginal treatments for HPV-related lesions vary in efficacy.Even in immunocompetent patients efficacy ranges are broad(20–80%). The overall response to many treatments is likely tobe lower in HIV-positive patients, and recurrence is 3.3 timesmore frequent.In the case of AIN, treatment decisions are based on size of thelesion, its location, and grade of histology. In managing theselesions in HIV-positive women, the least aggressive approach ispreferred. Radiation therapy should be avoided in the absence ofinvasive cancer.Treatment of CIN and AIN should not be modified for patients onHAART, nor should antiretroviral therapy be instituted or modifiedas part of treatment.The primary goal for Thailand is to reduce cervical cancer andmortality by detecting disease early, and treating it before itprogresses to invasive cancer.Thailand has ∼15 million women at risk for cervicalcancer, only 5% of whom have been screened in the previous 5years via the Pap smear campaign. A major problem is the shortageof trained cytopathologists to examine Pap smears, and limitedresources to followup women with positive Pap test results.outreach and education—to increase demandand enhance coverage,advocacy and policy—to ensure support for the programme,training,service delivery system—to ensure women haveaccess to screening and treatment that are acceptable to them andsustainable over time,a referral system—for women with advanced disease,information management—to monitor progress,equipment procurement, repair, and maintenance.A single-visit approach to cervical cancer prevention, linkingscreening and treatment, is appropriate for low-resource settings.This can be implemented at the lowest level of the health system,can be performed by trained nonphysicians, requires fewmaterials, and is relatively inexpensive. This approach alsoavoids the delay of sending specimens away for testing.In considering an alternative to conventional cytology, social andlogistical in addition to medical challenges need to be met. Keycomponents to be addressed include2CO-based system can be offered to any woman with abnormalities at the time of the screening. There may not be aconfirmed pathological diagnosis, but it is the intervention,rather than the diagnosis, that will prevent cervical cancer.Thus, although VIA may not be the most accurate test, it is themost efficient way to provide preventative services to themajority of women at risk.VIA is now established as a safe, effective, viable alternative tocytology-based screening for low resource settings. Cryotherapyusing a The major advantage is cost savings. A single visit approach islikely to be more effective and more cost-effective than multiplevisit strategies. A once-in-lifetime test for all women couldreduce cervical cancer incidence and mortality by up to 25%,dependent on coverage and age groups targeted. Good outcomes havebeen achieved in settings with a high prevalence of HIV–198.In 1999, a trial project based on the single visit approach wasinitiated in Roi Et province. The safe, acceptability, feasibility(SAFE) project was very successful. Three in four targeted womenpresented to hospital and mobile clinics in the first 12 weeks,exceeding recruitment goals .Trained and motivated nurses screened 5999 women over 6 months;13% were positive with VIA and offered treatment.Following their experience with SAFE, treated women were surveyed;< 2% felt they were not adequately informed about thetreatment, or were not satisfied about their decision to betreated. Most importantly, 96.6% said they would recommendthe service to friends and family.After screening or treatment, 4.9% of women presented again.Only 2.7% of visits concerned a minor complication such asvaginitis, cervicitis, or cramping, and there were no majorcomplications.Efforts are now focused on training more local nurses in VIA andcryotherapy. By May 2005, ∼ 100 000 women 30–45 yearsof age had been tested with VIA, and 8–10% were offeredtreatment with cryotherapy. Ten Thai provinces have now adoptedthe single visit approach to screening.Recognition of the importance of linking testingto treatment.Use of competency-based training methods to prepareservice providers, clinical supervisors, and master trainers.Use of mobile and static clinics for servicedelivery, ensuring easier access for women.Communication to build national consensusand support for the programme.Four key actions have contributed to the success of the singlevisit approach in Thailand.Helicobacter pylori,oncological infectious agents, that is, HBV, HPV, HIV,Epstein Barr virus, schistosomes, and carcinogens, most notably tobacco,lifestyle changes, particularly growingobesity and decreased exercise and physical fitness,changing age structure in many societies—smallerfamilies and longer life-spans mean that cancer, generally adisease of old age, will grow in prevalence.Four key areas will contribute to global cancer levels in comingdecades:prevention,screening/diagnosis,treatment,symptom management and health-related qualityof life leading to prolonged survival,end-of-life care.A number of global organisations are working with national andlocal groups to develop cancer control programmes that involvestakeholders at all levels, are appropriate to the patientpopulation, and are achievable and sustainable.Cancer control is a continuum where improved outcomes canbe achieved at many different levels:Organisations that have publicly stated their commitment to cancercontrol include the WHO IARC, World Charter Against Cancer 2000,WHO World Health Assembly, and the International Union AgainstCancer.The Global Initiative on Women's Cancer (GLOW) has identifiedthree areas of focus—gynaecological cancer , breast cancer, and tobacco control.prevention with prophylactic HPV vaccines,screening,new diagnostic tests,treatments to cure or prolong survival,Palliative care.Another key focus for GLOW is education through publications,websites, meetings, and satellite symposia at majorobstetrics/gynaecology and oncology meetings. GLOW can alsoprovide technical expertise in planning, implementation, andevaluation of cervical control programmes.GLOW supports a number of initiatives for cervical cancer and isdeveloping appropriate guidelines for their adoption:establishing a database for country-specificneeds assessment,integrating cervical cancer control intonational cancer plans and health programmes—including governmentsupport and early adoption of HPV vaccination,improving availability of treatment and care—bybuilding on existing resources to ensure that cervical cancerscreening is part of health promotion for older women.The short-term agenda for GLOW includes


Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes. MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer- and type-specific primer mediated PCR (GP/TS PCR). Both techniques were performed on paraffin embedded tissue sections. Results show disturbed MHC class I heavy chain expression in CIN I to CIN III, as well as in cervical carcinomas. Upregulated MHC class II expression on dysplastic epithelial cells was also found in the different CIN groups and carcinomas. Prevalence of HPV genotypes increased with the severity of the lesion, mainly due to the contribution of the HPV types 16 and 18. No correlation could be established between the presence of specific HPV genotypes and any MHC expression pattern in the different CIN groups or cervical carcinomas. In some cases these data were confirmed by RNA in situ hybridisation showing HPV 16 E7 transcripts in the same dysplastic/neoplastic cells from which MHC status was determined. The results indicate that local differences may exist in the type of cellular immune response to HPV induced lesions.


It is well established that renal allograft recipients (RARs) have an increased incidence of viral warts and premalignant and malignant cutaneous lesions, and the risk of their development increases in proportion to duration of graft survival. It has been postulated that, in addition to the effects of prolonged immunosuppression and previous sun exposure, human papillomaviruses (HPV) may also contribute to the carcinogenic process. In this study, the prevalence of HPV DNA was examined in a range of premalignant and malignant cutaneous tumours from 50 immunosuppressed patients  and 56 immunocompetent patients using Southern hybridisation as a low-stringency screening method and type-specific polymerase chain reaction (PCR) assays for eight HPV types. The combined results for renal allograft recipients show that HPV DNA was detectable in 79% of viral warts, 42% of premalignant keratoses, 33% of intraepidermal carcinomas, 43% of invasive squamous cell carcinomas and 16% of uninvolved skin specimens . In immunocompetent patients the pattern of HPV DNA prevalence was 100% for viral warts; 25% for keratoses, 23% for intraepidermal carcinomas, 22% for squamous cell carcinomas and 8% for uninvolved skin. No single HPV type predominated in tumour specimens from either group. More tumours were found to contain HPV DNA by Southern hybridisation analysis than PCR, indicating the presence of HPV types other than HPV 1, 2, 5, 6, 8, 11, 16 and 18 in some tumours. However, 'low cancer risk' HPV types 1, 2 and 6 as well as 'high cancer risk' HPV types 5 and 16 were specifically detected by PCR in a small number of neoplasms. These data suggest that multiple HPV types may contribute to cutaneous neoplasia in RARs and that they appear to act early in the process of carcinogenesis, perhaps by functioning as tumour promoters via stimulation of cell proliferation.


But regular daily intake may not be sufficient during pregnancy due to metabolic changes in the mother-to-be, and recent studies suggest that detection and treatment may be needed long before birth. These and other topics were discussed by scientists at a January 2004 symposium cosponsored by the Centers for Disease Control and Prevention, the National Center on Birth Defects and Developmental Disabilities, and the American Thyroid Association (ATA).Since the 1970s, epidemiologic studies have linked maternal thyroid insufficiency during gestation with fetal brain malformation, fetal death, and miscarriage. The fetus is wholly dependent on the maternal thyroid during the first 10–20 weeks of gestation. U.S. women generally get enough iodine, the elemental nutrient essential for synthesis of the thyroid hormone thyroxine  measured and thryoxine treatment applied if necessary, while the control mothers will remain untested until after their babies are delivered. Children from both groups will undergo developmental testing at ages 2 and 5 years. This study will rigorously evaluate the impact of both subclinical maternal hypothyroidism and hypothyroxinemia  on the IQ scores of the offspring, as well as the effect of prenatal treatment.John Lazarus, a senior lecturer in medicine at the University of Wales, United Kingdom, described his upcoming randomized clinical study of 22,000 women at 13–16 weeks’ gestation. An experimental group will have TAdditional discussions focused on the possible need for screening and treatment. “While it is not yet known whether early identification and treatment of thyroid deficiency will avoid fetal death and neuropsychological deficits in the offspring, it is clear that women themselves will benefit,” said James Haddow, medical director of the Foundation for Blood Research in Scarborough, Maine. “Many women go undiagnosed for longer periods of time, so that they lack the energy they need to function well in everyday life during their child’s early years, when the demands placed on them are greatest.”4 should be determined for the different stages of pregnancy. Another suggestion was to supplement prenatal vitamins with 150 micrograms of iodine (many currently contain little or none).Haddow contended that TSH measurement should be added to the list of tests routinely performed at the first prenatal visit . Lamm and other participants also suggested that normal levels for both TSH and T4 cut-off points for defining high risk. A TSH level of 2.5 milliunits per liter was proposed as a good initial cut-off. “This is a conservative cut-off,” said conference co-planner Joseph Hollowell, a professor of pediatrics at the University of Kansas Medical Center, “and it will prompt further investigation to see if there’s a real problem.”But scientists still need to agree on other matters, such as TSH and/or T


Chlamydia and gonorrhoea are major causes of morbidity among women in developing countries. Both infections have been associated with pregnancy-related complications, and case detection and treatment in pregnancy is essential. In countries without laboratory support, the diagnosis and treatment of cervical infections is based on the syndromic approach. In this study we measured the prevalence of chlamydia and gonorrhoea among antenatal care attendees in Botswana. We evaluated the syndromic approach for the detection of cervical infections in pregnancy, and determined if risk scores could improve the diagnostic accuracy.C trachomatis, N gonorrhoeae and other reproductive tract infections. Risk scores to identify attendees with cervical infections were computed based on identified risk factors, and their sensitivities, specificities, likelihood ratios and predictive values were calculated.In a cross-sectional study, 703 antenatal care attendees in Botswana were interviewed and examined, and specimens were collected for the identification of The prevalence of chlamydia was 8%, and gonorrhoea was found in 3% of the attendees. Symptoms and signs of vaginal discharge did not predict cervical infection, and a syndromic approach failed to identify infected women. Age (youth) risk factor most strongly associated with cervical infection. A risk score with only sociodemographic factors had likelihood ratios equivalent to risk scores which incorporated clinical signs and microscopy results. However, all the evaluated risk scores were of limited value in the diagnosis of chlamydia and gonorrhoea. A cut-off set at an acceptable sensitivity to avoid infected antenatal care attendees who remained untreated would inevitably lead to considerable over-treatment.C trachomatis and N gonorrhoeae in pregnant women in Botswana, a situation which is likely to apply to other countries in sub-Saharan Africa. Screening for cervical infections in pregnant women is an essential public health measure, and rapid tests will hopefully be available in developing countries within a few years.Although in extensive use, the syndromic approach is unsuitable for diagnosing cervical infections in antenatal care attendees in Botswana. None of the evaluated risk scores can replace this management. Without diagnostic tests, there are no adequate management strategies for  Neisseria gonorrhoeae or Chlamydia trachomatis can cause serious complications, such as ascending infections, infertility, cervical cancer, spontaneous abortion, premature delivery and low birth weight [Sub-Saharan Africa has the highest prevalence of gonorrhoea and chlamydia worldwide. These two sexually transmitted infections (STIs) have a major impact on health, particularly in women and neonates . A cervih weight . Epidemih weight ,4.C trachomatis and N gonorrhoeae, due to their association with maternal, foetal and infant morbidity. In developing countries, diagnosis of cervical infections is limited to the syndromic approach, using the 'vaginal discharge syndrome' (VDS) algorithm. In the early 1990s, the World Health Organization developed syndromic management guidelines as a case management of symptomatic STI patients in countries without laboratory support [It should be part of the mandate of the antenatal care programmes to diagnose and treat  support . Easily  support ,5-8. Sim support , and the support .The majority of women with a cervical infection are asymptomatic  and theiC trachomatis and N gonorrhoeae is reserved for women who present with vaginal discharge or lower abdominal pain and have either a positive risk assessment (age less than 21 years or complaints of yellow discharge) or yellow discharge or cervical mucopus on examination. These new recommendations are based on a non-validated study of female STI patients [It has become clear that vaginal discharge is poorly predictive of cervicitis, and in order to reduce over-treatment, the WHO recommends the incorporation of risk assessments in the syndromic management of cervical infections . In Botspatients . Risk fapatients ,13, and There are two parallel strategies to manage reproductive tract infections (RTIs) in pregnancy in Botswana. In addition to the syndromic management of women with symptoms, all antenatal care attendees are clinically screened for RTIs. The antenatal care guidelines recommend a routine speculum examination at the first antenatal visit, to "exclude genital infections, abnormalities and pelvic tumours" . It is nC trachomatis and N gonorrhoeae among antenatal care attendees in Botswana, and to assess the validity of the 'vaginal discharge syndrome and lower abdominal pain' algorithm in the diagnosis of cervicitis in pregnancy. We also evaluated the diagnostic accuracy of risk scores based on sociodemographic factors, specific symptoms or signs, or microscopy. The results from Botswana are used to discuss the management of cervicitis in pregnancy in sub-Saharan Africa.The aim of this study was to determine the prevalence of Participating in this study were 703 pregnant women who visited the 13 main facilities providing antenatal care in Gaborone, Botswana: 12 primary health clinics and one outpatient department. A proportionate sample of attendees was recruited from each location. This proportion corresponded to the percentage of all antenatal care attendees in Gaborone who visited that facility during the previous year. Facilities were visited one-by-one by a medical doctor between October 2000 and February 2001. In the majority of clinics, all attendees were included in the study. In the busiest clinics, only a sample of the attendees was included; the selection of attendees in these clinics was incidental. Approximately one out of every four antenatal care attendees in Gaborone was included in the study during the period of data collection. All participants gave written, informed consent. The only exclusion criterion was the use of antibiotics during the previous two weeks.A structured interview and information from the patient-held antenatal record were used to obtain data on sociodemographic and behavioural factors, current RTI symptoms, and diagnosis and prescribed treatment for such conditions earlier in the pregnancy. All patients underwent a genital examination; appropriate specimens were collected; and abnormal signs from external and internal genitalia were recorded in detail.C trachomatis and N gonorrhoeae. The swabs were placed in LCx® transport media, transported to the laboratory the same day, and stored at -20°C prior to batch processing. The LCx® Assays  were performed according to the manufacturer's instructions. A case of C trachomatis or N gonorrhoeae infection was defined as an individual with a positive LCR analysis.Urine was checked on site with a dipstick; all other specimens were analysed at the National Health Laboratory in Gaborone. Cervical swabs were obtained for ligase chain reaction (LCR) amplification technology for detection of Trichomonas vaginalis was placed in Stuart transport media. Before culturing, a wet-mount was made and examined for the presence of motile trichomonads by light microscopy, 100 × magnification. The swab was then agitated into a bottle of Diamond's modified medium. The bottles were incubated with indicators in Oxoid gaspack jars . Wet-mounts from the cultures were examined once a day for five days by light microscopy.A high vaginal swab for identification of Candida species was initiated by direct inoculation of a high vaginal swab on Saboraud plates on site, and Gram-stained smears and wet-mounts from high vaginal swabs were examined for budding yeast cells and pseudohyphae. A cervical smear was gram-stained to count polymorphonuclear leukocytes per high power field (PMN/HPF).Gram-stained vaginal smears were scored for bacterial vaginosis according to Nugent's criteria . CultureC trachomatis or N gonorrhoeae, or both. Factors which in the univariate analysis were associated with infection at a 0.2 level ) were included in multiple logistic regression analyses. We performed multiple logistic regression analyses on sociodemographic factors, symptoms, clinical signs and laboratory results, separately and combined. Due to the high number of variables, the full analysis of different factors' independent association with cervicitis had to be performed in two steps. First, multiple logistic regression analyses for the four variable categories were performed separately. The analysis was then extended to combining the factors from the different categories which were significantly independently associated with cervical infection in the first step.Data were analysed with the statistical package SPSS Version 11. We performed univariate analyses on all independent variables in our dataset which could be associated with cervical infection. The factors were within four categories: sociodemographic and behavioural factors, symptoms, clinical signs, and microscopy results. The dependent variable "cervicitis" was defined as infection with N gonorrhoeae and C trachomatis infections in the antenatal care. The first risk score level consists of only sociodemographic factors. At the second risk score level we added findings from the gynaecological examination. At the third level, we also allowed the results from microscopy of vaginal and cervical smears. Microscopy can be done on site, and thus all three risk score levels – the sociodemographic, the clinical and the microscopy score – can theoretically be performed during an antenatal care visit. The weights for each factor used in the risk scores were based on correspondent multiple logistic regression analysis models. The log of the OR for the variables in the model multiplied by 10 and rounded to the nearest whole number were used as weights for the respective factors in the risk scores [Three levels of risk scores were computed and retrospectively applied, and each of them were assessed for their usefulness as a diagnostic tool to manage k scores . The facReceiver Operating Characteristic (ROC) curves were used to compare the different risk scores. The ROC curve shows the sensitivity and specificity that correspond to each possible cut-off for the risk score. The validity of different diagnostic strategies  was assessed by measuring sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and positive and negative predictive values (PPV and NPV). The LCR-based laboratory diagnosis of cervical infection was used as the reference standard. In the evaluation and comparison of diagnostic strategies, we present two cut-offs for the risk scores, taken at a sensitivity of minimum 0.40 and 0.70.The study was approved by ethical committees in Botswana and in Norway.C trachomatis, and 21 (3%) with N gonorrhoea. T vaginalis was identified in 131 (19%) women and bacterial vaginosis in 268 (38%) women. Candida species were identified by microscopy and/or culture in 416 (59%) of the women. A total of 561 (80%) of the antenatal care attendees had one or more of these five reproductive tract infections.Of the 703 women, 67 (10%) had laboratory-confirmed cervical infection: 51 (8%) were infected with In spite of the high prevalence of cervical and vaginal infections in this study, few women confirmed symptoms when probed. Complaints of vaginal discharge were elicited from 119 (17%) of the women and lower abdominal pain from 58 (8%). Vaginal discharge was the most common clinical sign; candidalike discharge was found in 81 (12%) and other abnormal discharge was found in 227 (32%) of the women.C trachomatis and/or N gonorrhoeae infection are shown in Table T vaginalis.Demographic, behavioural, and obstetric factors; symptoms, signs, and simple laboratory tests; and their association with The factors which were independently associated with cervical infection are shown in Table N gonorrhoeae and C trachomatis infection, as illustrated with their ROC-curves  1.1, 95% CI: 0.6 to 1.9). Symptoms of vaginal discharge or lower abdominal pain in pregnancy proved inappropriate as an entry point to the VDS algorithm, with a LR+ of 0.94 (95% CI: 0.6–1.5). The current practice of clinical screening for signs of vaginal discharge (excluding candida-like discharge) also had low discriminative ability .Table All risk scores suffered from the choice between low sensitivity and low specificity. With a cut-off taken at an acceptable sensitivity of minimum 0.7, the risk score based on sociodemographic factors identifies 50 (75%) and misses 17 (25%) of the 67 cervical infections. Per true case treated, six pregnant women would be prescribed multiple antibiotic regimens unnecessarily. With a cut-off at a sensitivity of 0.4, the sociodemographic risk score identifies only 29 (43%) of the cervical infections. The majority of the cervical infections would remain untreated, and although over-treatment is reduced, four pregnant women would still be unnecessary treated with multiple antibiotics per infected women. The more comprehensive clinical and microscopy risk scores show similar results.C trachomatis infection, compared to rates between 6% in Tanzania and 13% in Cape Verde [Pregnant women are usually considered to be a low-risk population, but among antenatal care attendees in Botswana, the burden of reproductive tract infections is very high. The prevalence of cervical infections is 10%, and most of the infected women go undetected through normal antenatal care services. Published studies of STIs among pregnant women in other countries in sub-Saharan Africa show similar trends in the prevalence of cervical infections. In our study, 8% have a pe Verde . Gonorrhpe Verde ,21. AlthElicited symptoms of increased discharge or lower abdominal pain are not predictive of cervical infection in antenatal attendees in Botswana. These symptoms are non-specific; they are common in pregnancy, and their association with cervical infections is even lower among pregnant than among non-pregnant women . The VDSC trachomatis and N gonorrhoeae.To use the genital examination at the first antenatal care visit as a clinical screening tool for cervical infections is also unadvisable. According to the newly revised VDS algorithm in Botswana, symptoms or signs of yellow discharge are risk factors which should lead to treatment for cervical infections. In our study among antenatal care attendees, neither symptoms nor signs of yellow discharge are associated with cervical infection. In pregnancy, symptoms or signs of vaginal discharge in general, yellow discharge, or other specific discharge characteristics should not be used as criteria for treating N gonorrhoeae and C trachomatis. Our study concurs with a substantial body of knowledge indicating that the syndromic approach should be used neither as a case management of symptomatic women nor as a clinical screening tool to identify C trachomatis and N gonorrhoeae in antenatal care attendees in sub-Saharan Africa.Other studies from sub-Saharan Africa conclude that case management with the vaginal discharge syndrome has poor discriminatory ability in the diagnosis of cervicitis -27. SeveDespite extensive analyses, all computed risk scores were of limited value as screening tools in antenatal care attendees. They had poor discriminative ability, even in the study population in which they were computed and adapted to under optimal conditions. As the syndromic approach, the risk scores also resulted in a large number of undetected cervical infections and substantial over-treatment. Additionally, notification and treatment of sexual partners, an essential element of STI management, is difficult to justify when the majority of the identified women do not have an STI . A substC trachomatis and N gonorrhoeae has been a high priority since the 1990s [C trachomatis and N gonorrhoeae are now on the market [C trachomatis and N gonorrhoeae. Through the prevention of mother-to-child transmission of HIV programme, all health posts and clinics have lay workers who perform rapid tests for HIV. Simple tests for cervical infections performed by clinicians or lay workers may prove a feasible contribution to the improvement of diagnosis and the reduction of the disease burden of these conditions in this and similar settings.The development of simple, rapid tests for he 1990s . Major pe market ,32. The e market . So far,e market -36. In BC trachomatis and/or N gonorrhoeae in our study population. Thus age can be useful as a screening tool in the traditional sense, to minimise the number of standard diagnostic tests by identifying people with a higher-than-average prevalence of infection [Consistent with established knowledge on STI epidemiology ,31, youtnfection . If it wC trachomatis and N gonorrhoeae among antenatal care attendees in Botswana. Unfortunately, risk scores do not appear to improve the management of cervical infections in pregnancy substantially. To diagnose and treat asymptomatic cervical infections, and to reduce the massive overtreatment in the syndromic management, specific diagnostic tests are necessary. Screening for cervical infections in pregnant women is an essential public health measure, and rapid tests will hopefully be available in developing countries within a few years. In the temporary absence of such tests, health authorities in sub-Saharan Africa should consider reallocating their resources to other STI measures rather than diagnosing and treating gonorrhoea and chlamydia inadequately in antenatal care.Although the vaginal discharge syndrome does not discriminate between infected and uninfected women, the algorithm is in extensive use to diagnose and treat STI, sexually transmitted infection; VDS, vaginal discharge syndrome; PMN/HPF, polymorphonuclear leukocutes per high power field; OR, odds ratio; ROC, receiver operating characteristics; LR+ and LR-, positive and negative likelihood ratios; PPV and NPV, positive and negative predictive value; CI, confidence interval.The author(s) declare that they have no competing interests.MR contributed to the study design, was responsible for data collection and data analysis, and drafted the manuscript. MRa contributed to the study design and to formal and organisational aspects of the study. MV contributed to the study design, and led and performed the majority of the laboratory work. JS and PH supervised the study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7  and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer.


A histopathological study was undertaken on breast tissue dissected during the course of 207 consecutive forensic post-mortems on women over the age of 15 years in order to define the frequency and types of lesions found in Australian women. At least 10 blocks were obtained from each breast and a total of 4,738 blocks were examined. A particularly high frequency of atypical hyperplasia (12.6%), carcinoma in situ (13.0%), focal secretory change (24.1%) and perilobular haemangiomas (11.2%) was found. The radial scar, considered by some to be a precursor of infiltrating ductal carcinoma was found in 7.7% of the women.