The Present Scenario of Cervical Cancer Control and HPV Epidemiology in India: an Outline

Objective: To give a clear picture with epidemiological evidence about the present scenario of cervical cancercontrol and HPV in India. Design: Review of published studies, concentrating on recent systematic reviews,meta-analyses and large prospective studies. Conclusions and recommendations: Cervical cancer is unique amongcancers in that it can largely be prevented through screening and removal of precursor lesions. It is the secondmost common cancer among women worldwide and is the most common malignancy in developing countries,particularly in India. Nowadays, cervical screening for women is necessary because there are no signs andsymptoms of cervical precancers. The establishment of a prevention program is urgently required consideringboth screening and vaccination. But most women in India do not have access to effective screening programmes.It has been estimated that in India, even with a major effort to expand cytology services, it will not be possibleto screen even one-fourth of the population once in a lifetime in the near future. New HPV vaccines will alsohelp prevent HPV infection and the precancerous changes that lead to cervical cancer. The focus on detectionand prevention of cervical cancer must be emphasized in a highly populated country like India to prevent itsextensive spread.     

Epidemiologie,Prävention und Früherkennung des Zervixkarzinoms

Background

Persisting infections with human papillomaviruses (HPV) are the indisputable cause of cervical cancer. The development of HPV-based preventive procedures, HPV vaccination and HPV testing are currently leading to major changes in cervical cancer prevention programs worldwide. A reduction of HPV infections and cancer precursors has been observed for young women in many countries one decade after the introduction of HPV vaccination. The focus is now on the integration of new testing approaches for screening of populations with increasing vaccination rates.

Results and conclusion

A successful cervical cancer prevention program consists of various components including primary screening, triage of screening positives and colposcopy with biopsy to identify women with precursor cancer stages who require treatment. The role of primary screening is to identify a small subset of women with an increased risk of a precancerous stage, while the majority of women can be reassured that the risk is very low. Depending on the primary screening test, additional triage testing is required to decide who should be referred for colposcopy. Currently, there are three major approaches to cervical cancer screening: cervical cytology, HPV testing and HPV cytology co-testing. Several triage tests for HPV-positive women are currently being evaluated, including cytology, HPV genotyping, p16/Ki-67 cytology and various methylation tests. The increasing number of options for cervical cancer screening represent a challenge for clinical guidelines to remain up to date and comprehensible. The increasing complexity can lead to confusion among providers and women who participate in screening programs about the best approaches. Precision prevention is a novel approach to cervical cancer screening that integrates comprehensive risk data based on the individual medical history with test results for uniform, risk-based management decisions.

     

2012年美国宫颈癌筛查新指南解读

本文就2012年ACOG、ACS/ASCCP/ASCP指南中宫颈癌筛查的新建议及相关证据进行解读,并对宫颈癌筛查的新标志物、HPV检测新技术和未来可能的宫颈癌筛查新策略进行综述。2012年宫颈癌筛查新指南建议,宫颈癌筛查应从21岁开始,无论性生活开始的年龄或是否有其他行为相关的危险因素,对21岁以前的人群不应进行筛查。新指南还延长了细胞学检查的时间间隔：21~29岁的妇女细胞学检查间隔时间由过去的2年延长至3年,在30~65岁无高危因素的妇女中若HPV联合细胞学两项检查均为阴性可将筛查间隔时间延长至5年,并将终止筛查的年龄提前至65岁,因良性病变（无宫颈CIN2+或宫颈癌病史）而行子宫切除术的妇女不需要再进行筛查。但已接种疫苗妇女仍需继续同未接种疫苗的妇女一样按照指南进行宫颈癌筛查。最新的指南中将HPV联合细胞学检查作为30岁以上妇女的最佳筛查策略,并建议将HPV16、18分型检测作为分流HPV检测阳性而细胞学阴性患者的标准。HPVE6/E7mRNA、p16和Ki-67等新标志物的检测可能成为HPV检测阳性而细胞学检查阴性的患者进行分流管理的新生物学指标,并使筛查策略得到优化。     

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer,treatment rates and adverse obstetric outcomes in Australia,a high vaccination coverage country

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12–13 years) for the Australian cervical screening program. Two‐yearly cytology screening (ages 18–69 years) was compared to 5‐yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25–74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual‐based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre‐term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12–13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12–13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening.     

Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India

Cervical cancer is a leading cause of cancer death among women in low-income countries, with approximately 25% of cases worldwide occurring in India. We estimated the potential health and economic impact of different cervical cancer prevention strategies. After empirically calibrating a cervical cancer model to country-specific epidemiologic data, we projected cancer incidence, life expectancy, and lifetime costs (I$2005), and calculated incremental cost-effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent vaccination of girls before age 12, screening of women over age 30, and combined vaccination and screening. Screening differed by test (cytology, visual inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1 x , 2 x , 3 x per lifetime), and age range (35-45). Vaccine efficacy, coverage, and costs were varied in sensitivity analyses. Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28-57%) with HPV 16,18 vaccination alone, and 21-33% with screening three times per lifetime. Combining vaccination and screening three times per lifetime provided a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of $2), pre-adolescent vaccination followed by screening three times per lifetime using either VIA or HPV DNA testing, would be considered cost-effective using the country's per capita gross domestic product (I$3452) as a threshold. In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective.     

Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia

We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study 184 women treated for CIN 2 or 3 were prospectively monitored by cervical cytology and high-risk HPV testing 3, 6, 9, 12 and 24 months after treatment. Post-treatment CIN 2/3 was present in 29 women (15.8%). A positive high-risk HPV test 6 months after treatment was more predictive for post-treatment CIN 2/3 than abnormal cervical cytology (sensitivity 90% and 62% respectively, with similar specificity). At 6 months the negative predictive value of a high-risk HPV negative, normal smear, was 99%. Largely overlapping, partly different groups of women with post-treatment CIN 2/3 were identified by HPV testing and cervical cytology. Based on these results we advocate to include high-risk HPV testing in monitoring women initially treated for CIN 2/3. In case of a high-risk HPV positive test or abnormal cervical cytology, colposcopy is indicated. All women should be tested at 6 and 24 months after treatment and only referred to the population-based cervical cancer screening programme when the tests are negative on both visits.     

Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices

Cervical cancer (CC) represents the fourth most common malignancy affecting women all over the world and is the second most common in developing areas. In these areas, the burden from disease remains important because of the difficulty in implementing cytology-based screening programmes. The main obstacles inherent to these countries are poverty and a lack of healthcare infrastructures and trained practitioners. With the availability of new technologies, researchers have attempted to find new strategies that are adapted to low- and middle-income countries (LMIC) to promote early diagnosis of cervical pathology. Current evidence suggests that human papillomavirus (HPV) testing is more effective than cytology for CC screening. Therefore, highly sensitive tests have now been developed for primary screening. Rapid molecular methods for detecting HPV DNA have only recently been commercially available. This constitutes a milestone in CC screening in low-resource settings because it may help overcome the great majority of obstacles inherent to previous screening programmes. Despite several advantages, HPV-based screening has a low positive predictive value for CC, so that HPV-positive women need to be triaged with further testing to determine optimal management. Visual inspection tests, cytology and novel biomarkers are some options. In this review, we provide an overview of current and emerging screening approaches for CC. In particular, we discuss the challenge of implementing an efficient cervical screening adapted to LMIC and the opportunity to introduce primary HPV-based screening with the availability of point-of-care (POC) HPV testing. The most adapted screening strategy to LMIC is still a work in progress, but we have reasons to believe that POC HPV testing makes part of the future strategies in association with a triage test that still needs to be defined.     

Current status of cervical cancer and HPV infection in Korea

Cervical cancer is an important cause of cancer-related deaths in women in developing countries. In Korea, cervical cancer is the third leading cancer among females and is fifth highest in mortality. The persistent oncogenic human papillomavirus (HPV) infections are the greatest risk of developing cervical intraepithelial neoplasia and invasive cancer. The overall prevalence of HPV was 10.4% in Korea and strong risk factors for HPV infection included a young age at sexual debut. The National Cancer Screening Program, which includes cervical cancer screening, has the following principles: the main screening tool is the Papanicolaou test conducted by gynecologists, which targets all women age 30 and over, and which is done every 2 years. HPV DNA tests have not yet been permitted as a screening test for cervical cancer in Korea; however, these are conducted along with a Pap test for screening cervical cancer in the clinic. The use of prophylactic HPV vaccine has been accepted in Korea; The Korean Society of Gynecologic Oncology and Colposcopy''s recommendation for routine vaccination is for females aged 15-17 years with a catch-up vaccination recommended for females aged 18-26 years who have not been previously vaccinated. However, many people in Korea are not familiar with the HPV vaccine. Therefore, it is necessary to improve awareness for the disease and HPV vaccination and to establish the effective strategies to obtain funding for HPV vaccination. In the future, cervical cancer is expected to disappear throughout the world, including the Asia Pacific region, through a combination of vaccination and qualified screening programs for cervical cancer.     

Human papillomavirus vaccines versus cervical cancer screening

Prophylactic vaccination with human papillomavirus (HPV) virus-like particle (VLP) vaccines against HPV 16 and HPV 18, which are the cause of 70% or more of cervical cancers in women, has transformed our prospects for reducing the incidence of this disease on a global scale. HPV VLP vaccines are immunogenic, well tolerated and show remarkable efficacy, achieving >98% protection in randomised clinical trials against the obligate precursor lesions cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma in situ. The implementation of these vaccines as a public health intervention is, however, complex. Cervical cancer screening can be a highly effective secondary intervention, but in the developing world these programmes are either not available or are ineffective. HPV vaccination represents the most effective intervention in that scenario. In countries with successful well-organised cervical cancer screening programmes, such as the UK, the cost-effectiveness of vaccination as opposed to screening is a major factor. Screening will have to continue, as only two of the 15 oncogenic HPV types are in the vaccines and for two to three decades at least unvaccinated sexually active women will remain at risk for the disease. However, if both vaccination and screening are combined then the virtual elimination of cervical cancer and the other HPV 16 and 18-associated cancers is possible.     

Organization of screening programs in developing countries with reference to screening for cancer of the uterine cervix in India

Cancer of the uterine cervix is the leading female malignancy in developing countries such as India. Efforts for early detection by cervical cytology smears have been few, restricted to special situations, or short-term. No measurement of impact in terms of decline in mortality or incidence rates has been possible in India. However, a study by the Cytology Research Centre, New Delhi, on the natural history and biological behaviour of dysplasias provides evidence of the usefulness of screening to detect malignancy at early stages; both routine follow-up by cervical smears of women with dysplasia as well as screening of women attending gynaecological out-patient departments were used. This paper reviews the magnitude of the problem of uterine cervical cancer, the epidemiological aspects of the present situation in India, the efforts made for its control in different parts of the country and the problems encountered in organizing cervical cancer screening programs. Models of the approaches adopted are described, and guidelines are suggested which include the utilization of several approaches, including institution-based programs, extension of services to peripheral areas through mobile units, links with maternal care services, and establishment of referral systems. The need to develop human resources in cytology, in both medical and paramedical categories, is highlighted.     

The age-specific prevalence of human papillomavirus and risk of cytologic abnormalities in rural Nigeria: implications for screen-and-treat strategies

Cervical screening for carcinogenic human papillomavirus (HPV) infection is being considered for low-income countries. Effectiveness requires targeted screening in older women in whom prevalent infections are more likely to be persistent and predictive of precancer. Some studies in West Africa have found unusually high HPV prevalences across all adult ages, which may reduce the positive predictive value (PPV) of HPV-based screening, if positivity in older women does not sufficiently predict elevated risk. We conducted a population-based study in rural Nigeria to identify HPV prevalence and associated cervical abnormalities. Using stratified random sampling, we enrolled women age 15+. Nonvirgins had a cervical exam including liquid-based cytology and PCR HPV DNA testing from residual cytology specimens. Two-thirds of invited women participated, and 14.7% had detectable carcinogenic HPV, a proportion that did not decline with age (p-trend = 0.36) and showed slight peaks in the 15-29 and 60-69 age groups. Among women of the age typically considered for screen-and-treat programs (30-49 years), 12.8% were HPV positive, and the PPV for high-grade or worse cytology was 16.4%. Comparatively, women age < 30 were more likely to be HPV positive (18.9%, p = 0.03) with a lower PPV (4.2% p = 0.05). Among women age 50+ (typically excluded from screening in resource-poor settings because inexpensive treatment is not available), HPV positivity was 14.2% with a PPV of 13.9%. In Irun and similar settings where HPV does not decline with age, HPV-based screen-and-treat programs might be feasible for mid-adult women because prevalence is sufficiently low and positivity predicts elevated risk of more easily treated precancer.     

The impact of cytology screening and HPV vaccination on the burden of cervical cancer

Aim: To evaluate the impact of different strategies of human papillomavirus (HPV) vaccination on the burden of cervical cancer in Singapore. Methods: The incidence of cervical cancer was calculated using a Markov model with inputs based on Singapore data for the prevalence of HPV infection, socioeconomic characteristics and screening prevalence. The evaluation was performed for 10 scenarios: no screening, current opportunistic cytology screening, ideal optimal screening, universal adolescent HPV vaccination at 12‐years old alone and with catch‐up cohorts and combinations of screening and vaccination. Results: (1) The model prediction showed that cervical cancer cases were reduced by 6.5% using opportunistic screening, by 34.3% using optimized screening and by 63.9% with a universal HPV vaccination at 12 years of age. (2) Adding optimized screening, but not opportunistic screening, to a universal adolescent HPV vaccination program caused a moderate further reduction in cervical cancer cases. (3) No difference was discernable in the impact of vaccination introduction between the age groups <20, 20–24 and 25–29 years old. (4) The time required to halve the incidence of cervical cancer was 42 years for universal vaccination at the age of 12 but could be shortened by including catch‐up cohorts of women up to 40‐years old. Conclusion: A universal HPV vaccination program introduced between the ages of 12–29 is superior to cytology screening in reducing the burden of cervical cancer. However, in the next four decades of post‐vaccination era, optimizing the screening program remains the most important measure for cervical cancer prevention.     

Epidemiological Features of Human Papillomavirus (HPV) Infection among Women Living in Mainland China

Cancer of the cervix is the third most common cancer in women worldwide, more than 85% of the casesoccurring in developing countries such as China. In China, since a national cancer registry is already set up butwith geographically limited data generated, the burden of cervical cancer is believed to be underestimated. Highriskhuman papillomavirus (HR-HPV) prevalence among women attending routine cervical cancer screeningprograms has been shown to correlate well with cervical cancer incidence rates based on independently obtainedHPV prevalence data as well as findings for the worldwide cervical cancer burden. Therefore, reviewing dataon HR-HPV prevalence in population-based screening studies and hospital-based case studies will be importantin the context of better understanding the cervical cancer burden and for the evaluation of the potential impactof HPV vaccination in the country. With the advent of prophylactic vaccines, significant progress is likely tobe made in cervical cancer prevention. This article reviews available data on the HPV epidemiology over a12-year time period (2001-2012) in mainland China under different epidemiological aspects: by age group ofstudy population, by ethnicity, by geographic area, as well as time period. The authors also review the potentialacceptability of HPV vaccination among Chinese women.     

Health impact of delayed implementation of cervical cancer screening programs in India: A modeling analysis

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual-based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age-specific cancer incidence and mortality reductions associated with screening (once-in-a-lifetime among women aged 30–34 years) with one-visit visual inspection with acetic acid (VIA) and one- and two-visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one-visit VIA, two-visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point-of-care one-visit HPV testing in 5 years; and (3) 5-year delayed implementation of screening with current screening tests or point-of-care HPV testing. Immediate implementation of two-visit HPV testing with a switch to one-visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30- to 34-year-old women screened once between 2017 and 2026. Delayed implementation with a one-visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high-burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination.     

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.     

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.     

Impact of HPV testing in opportunistic cervical screening: Support for primary HPV screening in the United States

Human papillomavirus (HPV) testing for cervical screening increases diagnosis of precancer and reduces the incidence of cervical cancer more than cytology alone. However, real-world evidence from diverse practice settings is lacking for the United States (U.S.) to support clinician adoption of primary HPV screening. Using a population-based registry, which captures all cervical cytology (with or without HPV testing) and all cervical biopsies, we conducted a real-world evidence study of screening in women aged 30 to 64 years across the entire state of New Mexico. Negative cytology was used to distinguish cotests from reflex HPV tests. A total of 264 198 cervical screening tests (with exclusions based on clinical history) were recorded as the first screening test between 2014 and 2017. Diagnoses of cervical intraepithelial neoplasia grades 2 or 3 or greater (CIN2+, CIN3+) from 2014 to 2019 were the main outcomes. Of cytology-negative screens, 165 595 (67.1%) were cotests and 4.8% of these led to biopsy within 2 years vs 3.2% in the cytology-only group. Among cytology-negative, HPV tested women, 347 of 398 (87.2%) CIN2+ cases were diagnosed in HPV-positive women, as were 147 of 164 (89.6%) CIN3+ cases. Only 29/921 (3.2%) CIN3+ and 67/1964 (3.4%) CIN2+ cases were diagnosed in HPV-negative, cytology-positive women with biopsies. Under U.S. opportunistic screening, across a diversity of health care delivery practices, and in a population suffering multiple disparities, we show adding HPV testing to cytology substantially increased the yield of CIN2+ and CIN3+. CIN3+ was rarely diagnosed in HPV-negative women with abnormal cytology, supporting U.S. primary HPV-only screening.     

Cervical cancer: Can it be prevented?

Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol’s iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented.     

Cervical cancer screening

There is abundant evidence that cervical cancer screening with conventional cytology(CC)has reduced mortality from cervical cancer. Based on the evidence, CC has been implemented as a modality of the population-based screening for the last several decades in Japan. Several issues are currently faced during screening. For instance, very low coverage is one of the greatest unsolved problems. At the same time, a reliable system is required to monitor specimen adequacy and to calculate detection rates of not only invasive cancer, but also cervical intraepithelial neoplasia(CIN), for the quality control and evaluation of screening efficacy. Recently, two new modalities may be applicable for cervical cancer screening. One is liquid-based cytology(LBC)and the other is the HPV test. LBC and CC did not differ significantly in terms of sensitivity and specificity for detection of CIN2+or CIN3+. HPV tests are superior to CC in sensitivity but are inferior in specificity for detection of CIN2+or CIN3+. Because there is a possibility reducing mortality from and incidence of invasive cervical cancer, implementation of these modalities to Japan should be taken into consideration. Prior to this, however, it is necessary to organize a system to compare performance indicators reflecting the effectiveness of the new modalities to those of CC in a population-based screening. Also, these results must be disclosed for a steady perspective on the cervical cancer screening in Japan.     

Update on prevention and screening of cervical cancer

Cervical cancer is the third most common cause of cancer in women in the world. During the past few decades tremendous strides have been made toward decreasing the incidence and mortality of cervical cancer with the implementation of various prevention and screening strategies. The causative agent linked to cervical cancer development and its precursors is the human papillomavirus (HPV). Prevention and screening measures for cervical cancer are paramount because the ability to identify and treat the illness at its premature stage often disrupts the process of neoplasia. Cervical carcinogenesis can be the result of infections from multiple high-risk HPV types that act synergistically. This imposes a level of complexity to identifying and vaccinating against the actual causative agent. Additionally, most HPV infections spontaneously clear. Therefore, screening strategies should optimally weigh the benefits and risks of screening to avoid the discovery and needless treatment of transient HPV infections. This article provides an update of the preventative and screening methods for cervical cancer, mainly HPV vaccination, screening with Pap smear cytology, and HPV testing. It also provides a discussion of the newest United States 2012 guidelines for cervical cancer screening, which changed the age to begin and end screening and lengthened the screening intervals.