Search

Objective. Determine the extent and reasons why women with abnormal Pap smears drop out from diagnosis and treatment, and the relationship between women's socioeconomic characteristics and dropping out. Methods. Cross-sectional retrospective study. Analysis of secondary sources and household interviews with women with abnormal Pap smears seen in the public municipal system from 2009 to 2011. Results. Confirmed dropout in the study population was 18.3%. Women with the greatest probability of dropping out lived in homes where there were children under five (probability ratio [PR]: 2.4; 95% confidence interval [95%CI]: 1.2-4.8) and where there was overcrowding (PR: 2.9; 95%CI: 1.2-7.3). Women whose initial Pap smear was done in a primary care center had a 4.6 times greater probability of dropping out than those seen in a hospital (95%CI: 1.7-12.3). The main reasons reported for drop- ping out were problems with health services organization and domestic workload. Conclusions. Women's living conditions and the organization and quality of health services affect dropout from diagnosis and treatment of precancerous lesions. Strategies need to be developed that address social determinants of dropping out as a way to ensure effectiveness of cervical cancer screening programs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the utility of cytology and HPV testing in women from Mumbai, India, suspected of having cervical intraepithelial neoplasia (CIN) on visual inspection with acetic acid (VIA), Lugol''s iodine (VILI), or both. Method: The sensitivity, specificity, and predictive values of these tests for the detection of CIN 2 and/or 3 were evaluated in this cross-sectional study with 756 women suspected of having CIN on visual inspection. Results: There were 25 women with CIN 2, 20 with CIN 3, and 21 with invasive cancer. The sensitivity to detect CIN 3 lesions was 85.0% (95% CI, 62.1–96.8) and 70.0% (95% CI, 45.7–88.1) for cytology testing at the ASCUS and LSIL thresholds, respectively, and it was 89.5% (95% CI, 66.9–98.7) for HPV testing. The specificity to detect CIN 3 lesions was 94.5% (95% CI, 92.5–96.1) and 96.1% (95% CI, 94.4–97.5) for cytology testing at the ASCUS and LSIL thresholds, and it was 91.1% (95% CI, 88.5–93.2) for HPV testing. Conclusion: Cytology and HPV testing were both found to be accurate triaging methods for women suspected of having CIN on visual inspection, especially for those with CIN 3 lesions. [Copyright &y& Elsevier]

Objective: The aim of the study was to evaluate the role of alcohol drinking and patterns of consumption in oral cancer incidence and mortality in a cohort study using data from the Trivandrum Oral Cancer Screening Study, India. Methods: At baseline, the study participants completed a lifestyle questionnaire including items on frequency and duration of alcohol consumption. They were followed up for oral cancer incidence and mortality. Data from 32 347 subjects, of whom 134 eventually developed oral cancer, were analysed to estimate risk of oral cancer incidence and mortality according to drinking patterns, using a Cox regression model adjusted for age, religion, education, occupation, body mass index (BMI), standard of living index, chewing habits, smoking habits, and vegetable and fruit intake. Results: Current and past drinkers were each associated with significantly increased risk of developing oral cancer. The hazard ratio increased significantly by 49% (95% CI = 1–121%) among current drinkers and 90% (95% CI = 13–218%) among past drinkers. A significant dose–response relationship between intake frequency, duration and oral cancer risk (incidence and mortality) was observed. Conclusions: As with other lifestyle factors, alcohol intake plays an important role in oral carcinogenesis in this population, and understanding this role is relevant to developing public health policies targeting at-risk population. [ABSTRACT FROM AUTHOR]

Objective To evaluate oral cancer screening by visual inspection. Methods A cluster randomized controlled trial was initiated in Trivandrum district, Kerala, India. Of 13 population clusters, seven were randomly allocated to three rounds of screening between 1996 and 2004, while standard care was provided in six (control arm). An activity-based approach was employed to calculate costs associated with various components of the screening trial. Information on the resources used and on clinical events in each trial arm was derived from trial databases. Total costs for each cluster were estimated in 2004 United States dollars (US$). The incremental cost per life-year saved was calculated for all eligible individuals and for high-risk individuals (i.e. tobacco or alcohol users). Findings The proportion of oral cancers detected at an early stage (i.e. stage I or II) was higher in the intervention arm than the control arm (42% versus 24%, respectively). The incremental cost per life-year saved was US$ 835 for all individuals eligible for screening and US$ 156 for high-risk individuals. Oral cancer screening by visual inspection was performed for under US$ 6 per person. Conclusion The most cost-effective approach to oral cancer screening by visual inspection is to offer it to the high-risk population. Targeted screening of this group will ensure that screening can be offered at a reasonable cost in a limited-resource setting. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of loop electrosurgical excision procedure (LEEP) to treat cervical intraepithelial neoplasia (CIN) in rural India.Method: Women with CIN colposcopic features unsuitable for cryotherapy were treated with LEEP using a "see-and-treat" approach. Women with unsatisfactory colposcopy had diagnostic LEEP. Cure was defined as no clinical or histologic evidence of CIN at 1-year follow-up. Factors influencing cure rates were evaluated by chi(2) tests.Results: Of the 1,141 women who underwent LEEP (569 see-and-treat; 572 unsatisfactory colposcopy), 634 had histologically proven CIN. Of those, 489 reported for follow-up and 459 (93.9%) had no evidence of disease. Cure rates were 98.1% for women with CIN 1, 93.6% for CIN 2, and 85.0% for CIN 3. Patients with CIN 2-3 had significantly lower cure rates.Conclusion: Cure rates for LEEP provided by newly trained doctors in rural India were similar to those reported in the gynecological literature. [ABSTRACT FROM AUTHOR]

The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a κ-value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Visual inspection-based screening tests, such as visual inspection with 4% acetic acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to cytology in mass screening programs. To date, there is only limited information on the accuracy of these tests in detecting High-grade Squamous Intraepithelial Lesions (HSIL). Eleven cross-sectional studies involving 56,939 women aged 25-65 years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to evaluate the accuracy of VIA and VILI performed by health workers. A common protocol and questionnaire was used. For final diagnosis, all women were investigated with colposcopy and biopsies were taken when necessary. Data from the studies were pooled to calculate sensitivity, specificity and predictive values of the tests for the detection of HSIL. Of the screened women, 16.1% and 16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative predictive values for VIA were 76.8% (95% CI: 74.2-79.4%), 85.5% (95% CI: 85.2-85.8%), 9.4% (95% CI:8.8-10.8%) and 99.5% (95% CI:99.4-99.6%), respectively. The values were 91.7% (95% CI: 89.7-93.4%), 85.4% (95% CI: 85.1-85.7%), 10.9% (95% CI: 10.2-11.6%) and 99.8% (95% CI:99.7-99.9%), respectively for VILI. The range of sensitivity and specificity for VIA was 56.1-93.9% and 74.2-93.8%, respectively, between studies and were 76.0-97.0 % and 73.0-91.3% for VILI. VILI had a significantly higher sensitivity than VIA in detecting HSIL, but specificity was similar. VILI appears to be a more accurate visual test for use in screening and treatment programs in low-resource settings. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes — either organized or opportunistic — have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and... [ABSTRACT FROM AUTHOR]

Deals with cervical cancer screening strategies for developing countries. Magnitude of the problem of cervical cancer worldwide; Impact of HIV on the prevalence of cervical cancer in Africa; Average 5-year survival from cervical cancer in developing countries.

This section focuses on public health issues and social inequalities in cancer in Asia. Topics explored include socioeconomic factors which influence cancer profiles and mortality, the major types of cancer recorded in the region such as cervical, breast, and colorectal cancers, and the inadequacy of cancer health services in rural locations.

Background: Cancer burden in India is rapidly growing, with oral, breast, and uterine cervix being the three most commonly affected sites. It has a catastrophic epidemiological and financial impact on rural communities, the vast majority of whom are socio‐economically disadvantaged. Strengthening the health system is necessary to address challenges in the access and provision of cancer services, thus improving outcomes among vulnerable populations. Objective: To develop, test, and validate a health system capacity assessment (HSCA) tool that evaluates the capacity and readiness for cancer services provision in rural India. Methods: A multi‐method process was pursued to develop a cancer‐specific HSCA tool. Firstly, item generation entailed both a nominal group technique (to identify the health system dimensions to capture) and a rapid review of published and gray literature (to generate items within each of the selected dimensions). Secondly, tool development included the pre‐testing of questionnaires through healthcare facility visits, and item reduction through a series of in‐depth interviews (IDIs) with key local stakeholders. Thirdly, tool validation was performed through expert consensus. Results: A three‐step HSCA multi‐method tool was developed comprising: (a) desk review template, investigating policies and protocols at the state level, (b) facility assessment protocol and checklist, catering to the Indian public healthcare system, and (c) IDI topic guide, targeting policymakers, healthcare workforce, and other relevant stakeholders. Conclusions: The resulting HSCA tool assesses health system capacity, thus contributing to the planning and implementation of context‐appropriate, sustainable, equity‐focused, and integrated early detection interventions for cancer control, especially toward vulnerable populations in rural India and other low‐resource settings. [ABSTRACT FROM AUTHOR]

Background: Population-based screening for the common non-communicable diseases (NCD) is recommended but is difficult to implement in the hard-to-reach areas of low resourced countries. The objective of our pilot study was to evaluate the feasibility and the efficacy of delivering NCD screening services at home by trained community health workers (CHWs). Men and women aged 30-60 years residing in rural areas of India were targeted for screening.Methods: The CHWs made home visits to educate the participants about healthy lifestyles and symptoms of common cancers and counsel the tobacco/alcohol users to quit. They measured height, weight, blood pressure (BP) and random blood sugar for all and performed oral visual examination (OVE) to screen the tobacco/alcohol users for oral cancer. For cervical cancer screening, the women themselves provided self-collected vaginal samples that the CHWs delivered to the laboratory for high-risk Human Papillomavirus (HPV) detection. The women were not screened for breast cancer but were made aware of the common symptoms and the importance of early diagnosis. Further assessment of the screen-positive individuals and the women with breast symptoms was arranged at the nearest primary health center (PHC).Results: The CHWs screened 1998 men and 4997 women from 20 villages within 6 months; the refusal rate was less than 10%. High BP and sugar were detected in 32.6% and 7.5% participants respectively; hypertension and diabetes were confirmed in 42.3% and 35% respectively among those undergoing follow-up. Obesity prevalence was only 2.4%. More than 50% men were tobacco chewers. Of the total participants, 2.6% were positive on OVE, though no oral cancer was detected among them. HPV test was positive in 8.6% women and they were triaged with visual inspection after application of acetic acid (VIA) test for treatment either by thermal ablation (same visit) or by loop excision. VIA was positive in 14% of the HPV-positive women and 56.5% of them received same day ablative treatment. The VIA-negative women were advised follow up after 1 year. No breast cancer was detected among the 0.6% women complaining of breast symptoms.Conclusions: Delivery of NCD screening services at home by trained CHWs is feasible and well-accepted by our study population. [ABSTRACT FROM AUTHOR]

The evidence that high-risk HPV infections cause cervical cancers has led to two new approaches for cervical cancer control: vaccination to prevent HPV infections, and HPV screening to detect and treat cervical precancerous lesions. Two vaccines are currently available: quadrivalent vaccine targeting oncogenic HPV types 16, 18, 6, and 11, and bivalent vaccine targeting HPV 16 and 18. Both vaccines have demonstrated remarkable immunogenicity and substantial protection against persistent infection and high-grade cervical cancer precursors caused by HPV 16 and 18 in HPV-naïve women, and have the potential to prevent 70% of cervical cancers in adequately vaccinated populations. HPV vaccination is now implemented in national programs in 62 countries, including some low- and middle-income countries. The early findings from routine national programs in high-income countries are instructive to encourage low- and middle-income countries with a high risk of cervical cancer to roll out HPV vaccination programs and to introduce resource-appropriate cervical screening programs. [ABSTRACT FROM AUTHOR]

Objective: To address the value of visual inspection where HPV‐based screening is not yet available, we evaluated the real‐world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. Methods: A total of 206 133 women aged 30–59 years received two rounds of VIA/VILI screening for cervical cancer in 2006–2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. Results: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2‐year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%–83% of CIN2, 70%–86% of CIN3, and 88%–100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. Conclusion: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource‐restricted settings. Synopsis: Multiple rounds of visual inspection with quality assurance could act as a temporary substitutional method for cervical screening, where HPV DNA testing is not operational. [ABSTRACT FROM AUTHOR]

Background: This study presents the preliminary results of a randomized controlled trial (RCT) initiated in January 2006 in India to evaluate the effectiveness of clinical breast examination (CBE) in reducing breast cancer mortality as compared to a no‐screening control group reported significant downstaging in the intervention group. The present manuscript reports long‐term follow‐up outcomes. Methods: Women 30–69 years old from 133 intervention clusters and 141 control clusters were invited to participate. Women in the intervention arm underwent three rounds of CBE every 3 years. CBE‐positive women were reexamined by a physician, and triple‐assessment was performed on those confirmed to have abnormalities. All participants were followed through home visits and linkage with population‐based cancer registry. Results: Of the 55,843 eligible women in the intervention arm, 95.7% had CBE at least once and 11.5% were CBE‐positive. Breast cancers were diagnosed in 335 participants in the intervention group and 273 in the control group (N = 59,447). Age‐standardized incidence rate of early cancer was 30.4 of 100,000 in the intervention and 21.9 of 100,000 in the control group, with a rate ratio (RR) of 1.4 (95% confidence interval [CI], 1.1–1.8). The age‐standardized breast cancer mortality rates were 11.3 and 11.1 per 100,000 in intervention and control arms, respectively (RR, 1.1; 95% CI, 0.8–1.5) after 15 years. Five‐year breast cancer survival rates were 77.0% in the intervention and 71.2% in the control groups (overall p value =.043). Conclusions: Triennial CBE screening failed to demonstrate any mortality benefit despite achieving a shift toward earlier stage at detection and improved survival in the intervention arm. CBE is a valuable tool for diagnosis of breast cancer in symptomatic women especially in areas where mammography and/or breast cancer screening programs are not widely available. The authors demonstrated that an "early diagnosis" approach can be as effective as clinical breast examination screening in reducing breast cancer mortality. These observations have major policy implications. [ABSTRACT FROM AUTHOR]

Population-based cancer survival is a key measurement of cancer control performance linked to diagnosis and treatment, but benchmarking studies that include lower-income settings and that link results to health systems and human development are scarce. SURVCAN-3 is an international collaboration of population-based cancer registries that aims to benchmark timely and comparable cancer survival estimates in Africa, central and south America, and Asia. In SURVCAN-3, population-based cancer registries from Africa, central and south America, and Asia were invited to contribute data. Quality control and data checks were carried out in collaboration with population-based cancer registries and, where applicable, active follow-up was performed at the registry. Patient-level data (sex, age at diagnosis, date of diagnosis, morphology and topography, stage, vital status, and date of death or last contact) were included, comprising patients diagnosed between Jan 1, 2008, and Dec 31, 2012, and followed up for at least 2 years (until Dec 31, 2014). Age-standardised net survival (survival where cancer was the only possible cause of death), with 95% CIs, at 1 year, 3 years, and 5 years after diagnosis were calculated using Pohar-Perme estimators for 15 major cancers. 1-year, 3-year, and 5-year net survival estimates were stratified by countries within continents (Africa, central and south America, and Asia), and countries according to the four-tier Human Development Index (HDI; low, medium, high, and very high). 1 400 435 cancer cases from 68 population-based cancer registries in 32 countries were included. Net survival varied substantially between countries and world regions, with estimates steadily rising with increasing levels of the HDI. Across the included cancer types, countries within the lowest HDI category (eg, CÔte d'Ivoire) had a maximum 3-year net survival of 54·6% (95% CI 33·3−71·6; prostate cancer), whereas those within the highest HDI categories (eg, Israel) had a maximum survival of 96·8% (96·1−97·3; prostate cancer). Three distinct groups with varying outcomes by country and HDI dependant on cancer type were identified: cancers with low median 3-year net survival (<30%) and small differences by HDI category (eg, lung and stomach), cancers with intermediate median 3-year net survival (30–79%) and moderate difference by HDI (eg, cervix and colorectum), and cancers with high median 3-year net survival (≥80%) and large difference by HDI (eg, breast and prostate). Disparities in cancer survival across countries were linked to a country's developmental position, and the availability and efficiency of health services. These data can inform policy makers on priorities in cancer control to reduce apparent inequality in cancer outcome. Tata Memorial Hospital, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer. [ABSTRACT FROM AUTHOR]

Background: Despite the high burden of cervical cancer, access to preventive measures remains low in India. A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer. We projected the effect of single-dose quadrivalent HPV vaccination in India in comparison with no vaccination or to a two-dose schedule.Methods: In this modelling study, we adapted an HPV transmission model (EpiMetHeos) to Indian data on sexual behaviour (from the Demographic and Health Survey and the Indian National AIDS Control Organisation), HPV prevalence data (from two local surveys, from the states of Tamil Nadu and West Bengal), and cervical cancer incidence data (from Cancer Incidence in Five Continents for the period 2008-12 [volume XI], and the Indian National Centre for Disease Informatics and Research for the period 2012-16). Using the model, we projected the nationwide and state-specific effect of HPV vaccination on HPV prevalence and cervical cancer incidence, and lifetime risk of cervical cancer, for 100 years after the introduction of vaccination or in the first 50 vaccinated birth cohorts. Projections were derived under a two-dose vaccination scenario assuming life-long protection and under a single-dose vaccination scenario with protection duration assumptions derived from International Agency for Research on Cancer (IARC) India vaccine trial data, in combination with different vaccination coverages and catch-up vaccination age ranges. We used two thresholds to define cervical cancer elimination: an age-standardised incidence rate of less than 4 cases per 100 000 woman-years, and standardised lifetime risk of less than 250 cases per 100 000 women born.Findings: Assuming vaccination in girls aged 10 years, with 90% coverage, and life-long protection by two-dose or single-dose schedule, HPV vaccination could reduce the prevalence of HPV16 and HPV18 infection by 97% (80% UI 96-99) in 50 years, and the lifetime risk of cervical cancer by 71-78% from 1067 cases per 100 000 women born under a no vaccination scenario to 311 (80% UI 284-339) cases per 100 000 women born in the short term and 233 (219-252) cases per 100 000 women born in the long term in vaccinated cohorts. Under this scenario, we projected that the age-standardised incidence rate threshold for elimination could be met across India (range across Indian states: 1·6 cases [80% UI 1·5-1·7] to 4·0 cases [3·8-4·4] per 100 000 woman-years), while the complementary threshold based on standardised lifetime risk was attainable in 17 (68%) of 25 states, but not nationwide (range across Indian states: 207 cases [80% UI 194-223] to 477 cases [447-514] per 100 000 women born). Under the considered assumptions of waning vaccine protection, single-dose vaccination was projected to have a 21-100% higher per-dose efficiency than two-dose vaccination. Single-dose vaccination with catch-up for girls and women aged 11-20 years was more impactful than two-dose vaccination without catch-up, with reduction of 39-65% versus 38% in lifetime risk of cervical cancer across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts.Interpretation: Our evidence-based projections suggest that scaling up cervical cancer prevention through single-dose HPV vaccination could substantially reduce cervical cancer burden in India.Funding: The Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background: The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.Methods: The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.Results: Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.Conclusions: Single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result. [ABSTRACT FROM AUTHOR]

Background: We conducted a Pattern-of-care (POC) study at two premier-most public-funded oncology centers in Morocco to evaluate delays in care continuum and adherence to internationally accepted treatment guidelines of cervical cancer.Method: Following a systematic sampling method, cervical cancer patients registered at Centre Mohammed VI (Casablanca) and Institut National d'Oncologie (Rabat) during 2 months of every year from 2008 to 2017, were included in this retrospective study. Relevant information was abstracted from the medical records.Results: A total of 886 patients was included in the analysis; 59.5% were at stage I/II. No appreciable change in stage distribution was observed over time. Median access and treatment delays were 5.0 months and 2.3 months, respectively without any significant temporal change. Concurrent chemotherapy was administered to 57.7% of the patients receiving radiotherapy. Surgery was performed on 81.2 and 34.8% of stage I and II patients, respectively. A very high proportion (85.7%) of operated patients received post-operative radiation therapy. Median interval between surgery and initiation of radiotherapy was 3.1 months. Only 45.3% of the patients treated with external beam radiation received brachytherapy. Radiotherapy was completed within 10 weeks in 77.4% patients. An overall 5-year disease-free survival (DFS) was observed in 57.5% of the patients - ranging from 66.1% for stage I to 31.1% for stage IV. Addition of brachytherapy to radiation significantly improved survival at all stages. The study has the usual limitations of retrospective record-based studies, which is data incompleteness.Conclusion: Delays in care continuum need to be further reduced. Increased use of chemoradiation and brachytherapy will improve survival further. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence and mortality rates are increasing rapidly in many low‐income and middle‐income countries. A demonstration project was implemented in Morocco in collaboration with the Ministry of Health to assess the feasibility, acceptability, and challenges of implementing CRC screening through routine primary care facilities. Methods: The objective of the project was to screen 10,000 men and women aged 50 to 75 years through 10 primary health centers (PHCs) in 2 provinces. All eligible men and women attending the selected PHCs were offered the fecal immunochemical test (FIT). Stool specimens brought to the PHCs were tested immediately by trained nurses. FIT‐positive individuals were referred to the National Oncology Institute for colonoscopy. Results: In total, 9763 eligible men and women were screened by FIT between June 2017 and May 2019; most (73.3%) were women. The test was positive in 460 participants (4.7%). Among the individuals who had positive FIT results, 62.6% underwent colonoscopy. The main reasons for noncompliance to colonoscopy were competing life priorities (15.4%), other health problems (13%), and fear of getting a cancer diagnosis (12.3%). As the number of referrals to colonoscopy increased, the waiting time for the procedure increased, resulting in a drop in compliance. The detection rates of advanced adenomas and CRC were 4.0 in 1000 and 0.5 in 1000 individuals screened, respectively. Conclusions: An effective strategy to reach the target populations (especially men), a pragmatic assessment of the health system's capacity to deal with large numbers of referrals, and a formal cost‐effectiveness analysis are essential before making any decision to introduce CRC screening in Morocco. The performance of colorectal cancer screening with the fecal immunochemical test offered through existing health infrastructure in Morocco is described. The report highlights facilitators and challenges that must be considered before making any decision to introduce colorectal cancer screening in low‐income and middle‐income countries. [ABSTRACT FROM AUTHOR]

Since the publication of the 2018 FIGO Cancer Report, giant strides have been made in the global effort to reduce the burden of cervical cancer, with the World Health Organization (WHO) rolling out a global strategy for cervical cancer elimination, aiming for implementation by 2030. In over 130 countries, including low- and middle-income countries, HPV vaccination is now included in the national program. Screening has seen major advances with wider implementation of HPV testing. These interventions will take a few years to show their impact. Meanwhile, over half a million new cases are added each year. FIGO's revised staging of cervical cancer (2018) has been widely implemented and retrospective analyses of data based on the new staging have been published. Minimally invasive surgery has been shown to be disadvantageous in women with cervical cancer. This chapter discusses the management of cervical cancer based on the stage of disease, including attention to palliation and quality of life issues. [ABSTRACT FROM AUTHOR]

Background: Cryotherapy is standard practice for treating patients with cervical precancer in see-and-treat programmes in low-income and middle-income countries (LMICs). Because of logistical difficulties with cryotherapy (eg, the necessity, costs, and supply chain difficulties of refrigerant gas; equipment failure; and treatment duration >10 min), a battery-operated thermal ablator that is lightweight and portable has been developed. We aimed to compare thermal ablation using the new device with cryotherapy.Methods: We report the pilot phase of a randomised controlled trial in routine screen-and-treat clinics providing cervical screening using visual inspection with acetic acid (VIA) in Lusaka, Zambia. We recruited non-pregnant women, aged 25 years or older, who were eligible for ablative therapy. We randomly assigned participants (1:1:1) to thermal ablation, cryotherapy, or large loop excision of the transformation zone (LLETZ), using computer-generated allocation. The randomisation was concealed but the nurses providing treatment and the participants were unmasked. Thermal ablation was achieved using the Liger thermal ablator (using 1-5 overlapping applications of the probe heated to 100°C, each application lasting for 40 s), cryotherapy was carried out using the double-freeze technique (freeze for 3 min, thaw for 5 min, and freeze again for 3 min), and LLETZ (using a large loop driven by an electro-surgical unit to excise the transformation zone) was done under local anaesthesia. The primary endpoint was treatment success, defined as either human papillomavirus (HPV) type-specific clearance among participants who were positive for the same HPV type at baseline, or a negative VIA test at 6-month follow-up, if the baseline HPV test was negative. Per protocol analyses were done. Enrolment for the full trial is ongoing. Here, we present findings from a prespecified pilot phase of the full trial. The final analysis of the full trial will assess non-inferiority of the groups for the primary efficacy endpoint. The study is registered with ClinicalTrials.gov, number NCT02956239.Findings: Between Aug 2, 2017, and Jan 15, 2019, 750 participants were randomly assigned (250 per group). 206 (84%) participants in the cryotherapy group, 197 (81%) in the thermal ablation group, and 204 (84%) in the LLETZ group attended the 6-month follow-up examination. Treatment success was reported in 120 (60%) of 200 participants in the cryotherapy group, 123 (64%) of 192 in the thermal ablation group, and 134 (67%) of 199 in the LLETZ group (p=0·31). Few participants complained of moderate to severe pain in any group immediately after the procedure (six [2%] of 250 in the cryotherapy group, four [2%] of 250 in the thermal ablation group, and five [2%] of 250 in the LLETZ group) and 2 weeks after the procedure (one [<1%] of 241 in the cryotherapy group, none of 242 in the thermal ablation group, and two [<1%] of 237 in the LLETZ group). None of the participants reported any complication requiring medical consultation or admission to hospital.Interpretation: Results from this pilot study preliminarily suggest that thermal ablation has similar treatment success to cryotherapy, without the practical disadvantages of providing cryotherapy in an LMIC. However, the study was not powered to establish the similarity between the techniques, and results from the ongoing randomised controlled trial are need to confirm these results.Funding: US National Institutes of Health. [ABSTRACT FROM AUTHOR]

Abstract Objective Self-collected HPV testing could substantially reduce disparities in cervical cancer screening, with slightly lower sensitivity compared to physician-collected specimens cross-sectionally. We aimed to evaluate the comprehensive long-term performance of self-collected HPV testing prospectively. Methods In 1999, 1997 women were screened by HPV testing on self-collected and physician-collected samples, cytology and visual inspection with acetic acid (VIA) and followed up in 2005, 2010 and 2014, respectively. HPV testing was performed with Hybrid Capture II. Prospective performance, baseline clinical efficiency, and 15-year cumulative risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were analyzed. Results Self-collected HPV testing prospectively detected 83.3% (95% CI:74.9%,89.3%), 70.3% (95% CI:62.5%,77.2%) and 63.3% (95% CI:55.7%, 70.2%) of cumulative CIN2+ at 6-year, 11-year and 15-year follow-up, respectively. Relative cumulative sensitivity of physician-collected HPV testing versus self-collected HPV testing was stable over 15 years at about 1.16. Cumulative sensitivity of self-collected HPV testing was comparable to cytology and significantly higher than VIA. Among women positive by self-collected HPV testing at baseline, 26.2% (95% CI:21.5%, 30.9%) developed CIN2+ during 6-year follow-up and no difference was observed with physician-collected HPV testing even 15 years after baseline. Negative self-collected HPV results provided greater protection against CIN2+ than VIA and ascertained CIN2+ cumulative incident rates as low as 1.1% at the 6-year follow-up. Conclusions Self-collected HPV testing demonstrates lower sensitivity than physician-collected HPV testing but performs comparably to cytology prospectively and provides satisfactory assurance against CIN2+, indicating an alternative role in cervical cancer primary screening with five-year interval as an option especially in low-resource settings. Highlights • There is a declined sensitivity by 16% of self-sampling versus physician-sampling using HC2 during 15-year prospectively. • Self-collected HPV testing performed comparably to cytology and superior to VIA during whole course of 15 years. • Baseline negative self-collected HPV result ascertained low cumulative CIN2+ risk as 1.1% during 6-year period. • Self-collected HPV testing plays an alternative role in cervical cancer screening with 5-year interval especially in LMICs. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Although the efficacy of the HPV vaccine in preventing the development of cervical pre-malignant lesions has been well demonstrated, the efficacy of the HPV vaccine in preventing HPV infection in the upper respiratory tract has been poorly studied.Methods: In the context of the IARC cohort study of two versus three doses of HPV vaccine in India, we compared the HPV type prevalence in the oral cavity of women vaccinated with three doses, two doses, or a single dose of quadrivalent HPV vaccine with that of unvaccinated women. A total of 997 oral samples, from 818 vaccinated women and 179 unvaccinated women, were collected at three study sites. All the participants were sexually active at the time of sample collection.Results: The age-standardized proportion (ASP) of HPV16/18 infections was 2.0 % (95 % CI, 1.0-3.0 %) in vaccinated women and 4.2 % (95 % CI, 1.2-7.2 %) in unvaccinated women. HPV16 was detected in 3.5 % of single-dose recipients, 1.2 % of two-dose recipients (days 1 and 180), and 1.5 % of three-dose recipients (days 1, 60, and 180), whereas 3.3 % of the unvaccinated women tested positive for HPV16. The same trend was observed for HPV18.Discussion: Our findings agree with those of previous studies on the efficacy of HPV vaccination in reducing oral HPV infections and provide indications that a single vaccine dose may be less efficient than two or three doses in preventing oral HPV infection. [ABSTRACT FROM AUTHOR]

Background: Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries. Methods: In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts. Findings: Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women. Interpretation: We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To describe the effectiveness of cryotherapy for treating women who were histologically confirmed to have cervical intraepithelial neoplasia (CIN) in India. Methods: Data were analyzed retrospectively from screening projects that collected data from January 2001 to May 2008 in Trivandrum, India. Women with CIN were appropriately treated with cryotherapy by a trained nurse or physician and followed up for cure, adverse events, and complications. Cure was defined as absence of CIN during any follow-up visit at least 1 year after treatment. Results: Among 236 women identified with CIN and appropriately treated with cryotherapy, 173 (81.6%) were followed up (158 CIN 1 and 15 CIN 2 cases). The percentage cure for CIN 1 and 2 lesions was 93.0% and 86.7% respectively. An odds ratio of 0.2 (95% confidence interval, 0.0–0.9) was observed for treatment received more than 2 months after screening as compared with treatment received within 2 months. Complications were observed in 1.2% of treated women and adverse events (discharge and mild pain) in 26.6%. Conclusion: The study affirms that trained mid-level providers can appropriately perform cryotherapy in primary healthcare services and that expanding such services in low-resource settings would increase the availability and accessibility of precancer treatment. [Copyright &y& Elsevier]

Abstract: Objective: To describe phase 1 of an organized cytology screening project initiated in Thailand by the Ministry of Public Health and the National Health Security Office. Methods: Women aged 35–60years were encouraged to undergo cervical screening in primary care units and hospitals through awareness programs. Papanicolaou smears were processed and reported at district or provincial cytology laboratories. Women with normal test results were advised to undergo repeat screening after 5years, while those with precancerous and cancerous lesions were referred for colposcopy, biopsy, and treatment. Information on screening, referral, investigations, and therapy were logged in a computer database. Results: Between 2005 and 2009, 69.2% of the 4030833 targeted women were screened. In all, 20991 women had inadequate smears; 27253 had low-grade squamous intraepithelial lesions; 15706 had high-grade squamous intraepithelial lesions; and 2920 had invasive cancers. Information on the management of precancerous lesions was available for only 17.4% of women referred for colposcopy. Conclusion: Although follow-up data on women with positive test results were inadequately documented, the present findings indicate that provision of cytology services through the existing healthcare system is feasible. [Copyright &y& Elsevier]

Background & objectives: Even though Kerala State is well-known for its egalitarian policies in terms of healthcare, redistributive actions and social reforms, and its health indicators close to those of high-resource countries despite a poor per-capita income, it is not clear whether socio-economic disparities in terms of life expectancy are observed. This study was therefore carried out to study the impact of socioeconomic level on life expectancy in individuals living in Kerala. Methods: A cohort of 1,67,331 participants aged 34 years and above in Thiruvananthapuram district, having completed a lifestyle questionnaire at baseline in 1995, was followed up for mortality and cause of death until 2005. Survival estimates were based on the participants' vital status and death rates were calculated separately for men and women and for several socio-economic factors, stratified by age. Results: At 40 years, men and women were expected to live another 34 and 37 years, respectively. Life expectancy varied across the participants' different socio-economic categories: those from high income households with good housing conditions, materially privileged households and small households, had a 2-3 years longer life expectancy as compared to the deprived persons. Also, those who went to college lived longer than the illiterates. The gaps between categories were wider in men than in women. Interpretation & conclusions: Socio-economic disparity in longevity was observed: wealthy people from Kerala State presented a longer life expectancy. [ABSTRACT FROM AUTHOR]

Abstract: Cervical cancer that is associated with high-risk human papillomaviruses (HPV) is the most common malignancy in Indian women. Therefore, the establishment of a prevention program is urgently required considering both vaccination and screening. However, relatively little is known about the prevalence of the different HPV types in cervical cancers in different regions of India, particularly central India. In this study, we have determined the HPV type distribution in 180 cervical cancers of women from Sevagram, a rural area from central India. In addition, we have analyzed other epithelial cancers that are known to be in part associated with high-risk HPV infection, i.e. oral (n =65), vulva and vagina (n =7) and penis (n =7). Approximately 93% of cervical cancers were positive for one or more of the high-risk HPV types. HPV16 was the predominant type being present in 81.7% of the cases. The remaining most predominant high-risk HPV types were: 18, 31, 35, 45, 56 and 59. Oral and vulva/vagina cancers were exclusively associated with HPV16, 27.7% and 70%, respectively. None of penile cancers was found positive for any of the high-risk HPV types. These data show that HPV16 vaccination in this geographical region will have considerable impact on the prevention of cervical and other epithelial cancers. [Copyright &y& Elsevier]

Objectives: The objectives of this study was to establish whether combined screening with visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) improves detection of cervical intraepithelial neoplasia 2–3 (CIN 2–3) lesions and cancer beyond chance, compared with screening with VIA alone or VILI alone; and to estimate the extra number of false-positive (FP) results per additional disease case found with the combined test, and to estimate the additional costs involved. Setting: Ten cross-sectional studies in Burkina Faso, Congo, Guinea, India, Mali and Niger, between 1999 and 2003. Methods: Using a common protocol, health workers screened 56,147 women aged 25–65 years with VIA and VILI. All women underwent a colposcopy examination and biopsies were taken when necessary. The disease reference standard was histology or negative colposcopy. A positive result on the combined test was defined if either VIA or VILI were positive. The accuracy of the combined test compared with VIA alone or VILI alone was evaluated using likelihood ratios. Results: The estimated sensitivity and specificity were 81.3% and 87.3%, respectively, for VIA; 91.5% and 86.9% for VILI; and 92.9% and 83.5% for the combined test. The ratio of the positive likelihood ratios of the combined test and VIA alone for CIN 2–3 lesions and cancer was 0.88 (95% confidense interval [CI]: 0.86–0.90), favouring use of VIA alone. The ratio of the negative likelihood ratios was 0.40 (95% CI: 0.37–0.47), favouring use of the combined test. Similar results were obtained when the combined test was compared with VILI alone. Assuming equivalent performance of VIA alone and the combined test with a disease prevalence of 2%, there will be about 16.0 (95% CI: 13.6–18.8) additional FPs for each additional true positive (TP) detected if the combined test is used. This number will be 121.1 (95% CI: 75.4–194.6) if VILI is considered as the single test. Conclusions: At the trade-off point between the combined test and VIA alone or VILI alone, given the numbers of additional FP results involved for each additional TP case of disease that were found, it would be more likely that settings already using VIA would advocate combined testing, and for settings using VILI to opt for the single test. The additional costs (per 1000 women) incurred with the combined test would be International $4117.68 versus either of the tests above. [ABSTRACT FROM AUTHOR]

The IARC monographs recently classified chewing betel quid without tobacco as a human carcinogen. Several studies in Taiwan have reported that betel quid without tobacco may increase the risk of oral precancers such as oral leukoplakia and oral submucous fibrosis. However in India, since most betel quid chewers prefer to add tobacco to the quid, the independent effect of betel quid on the risk of oral precancers is difficult to assess and has not yet been fully explored. We conducted a large case-control study in Kerala, India, including 927 oral leukoplakia cases, 170 oral submucous fibrosis cases, 100 erythroplakia cases, 115 multiple oral precancer cases and 47,773 controls. The focus of this reanalysis is on the minority of individuals who chewed betel quid without tobacco. Among nonsmokers and nondrinkers, chewing betel quid without tobacco conferred ORs of 22.2 (95%CI = 11.3, 43.7) for oral leukoplakia, 56.2 (95%CI = 21.8, 144.8) for oral submucous fibrosis, 29.0 (95%CI = 5.63, 149.5) for erythroplakia and 28.3 (95%CI = 6.88, 116.7) for multiple oral precancers, after adjustment for age, sex, education and BMI. Dose-response relationships were observed for both the frequency and duration of betel quid chewing without tobacco on the risk of oral precancers. In conclusion, our study supports the hypothesis that chewing betel quid without tobacco elevates the risks of various oral precancers. [ABSTRACT FROM AUTHOR]

Genomic instability in repeated DNA sequences is exhibited by a variety of cancer types, including oral squamous cell carcinoma. Exposure to carcinogenic compounds may further increase the instability. We have used Inter-Simple Sequence Repeat (Inter-SSR) PCR methodology to detect genetic alterations in 37 oral cancer patients who had chewed betel-quid. Thirty-eight percent of DNA from tumors had genomic alterations in the sequences flanked by (CA)8 and (GT)8 repeats. Patients with tumor DNAs harboring genomic alterations had a two-fold higher consumption of betel-quid than patients without alterations in tumor DNA. Matched normal and tumor DNAs were also screened for microsatellite instability where four patients (10.8%) showed alterations in at least one microsatellite marker but there was no relationship between this phenotype and betel-quid chewing. These data indicate that exposure to carcinogens present in the betel-quid may contribute to genomic instability detected by inter-SSR PCR in a subset of oral tumors. [Copyright &y& Elsevier]

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation. [ABSTRACT FROM AUTHOR]

Examples of successful implementations of national cancer control plans in low-income or middle-income countries remain rare. Morocco, a country where cancer is already the second leading cause of death after cardiovascular diseases, is one exception in this regard. Population ageing and lifestyle changes are the major drivers that are further increasing the cancer burden in the country. Facing this challenge, the Moroccan Ministry of Health has developed a we l planned and pragmatic National Plan for Cancer Prevention and Control (NPCPC) that, since 2010, has been implemented with government financial support to provide basic cancer care services across the entire range of cancer control. Several features of the development and implementation of the NPCPC and health-care financing in Morocco provide exemplars for other low-income and middle-income countries to follow. Additionally, from the first 5 years of NPCPC, several areas were shown to require further focus through implementation research, notably in strengthening cancer awareness, risk reduction, and the referral pathways for prevention, early detection, treatment, and follow-up care. Working together with a wide range of stakeholders, and engagement with stakeholders outside the health-care system on a more holistic approach can provide further opportunities for the national authorities to build on their successes and realise the full potential of present and future cancer control efforts in Morocco. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Contribution of Six Risk Factors to Achieving the 25x25 Non-Communicable Disease Mortality Reduction Target: A Modelling Study," by Vasilis Kontis et al. in the August 2, 2014 issue.

A letter to the editor is presented in response to the article "Systems analysis of real-world obstacles to successful cervical cancer prevention in developing countries," by E. J. Suba and colleagues.

Abstract: The clearly higher sensitivity and reproducibility of human papillomavirus (HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) has led to widespread calls to introduce it as the primary screening test. The main concern has been its lower specificity, due to the fact that it cannot separate transient from persistent infections, and only the latter are associated with an increased risk of high-grade CIN and cancer. Thus, even proponents of HPV testing generally only recommend it for women over the age of 30 years (or in some cases 35 years). If HPV testing is to reach its full potential, new approaches with better specificity are needed, either as triage tests for HPV positive women or, if the high sensitivity of HPV DNA testing can be maintained, as alternate primary screening modalities. Approaches that may useful in this regard, especially as triage tests, include HPV typing, methylation (and consequent silencing) of host and viral genes, and new cytologic methods, such as p16INK4a staining, which attempt to identify proliferating cells. At an earlier stage of development are direct methods based on detection of HPV E6 or E7 proteins. Recent progress and current status of these methods is discussed in this chapter. The current status of visual inspection (VIA and VILI) methods is also surveyed and progress on self-sampling is reviewed. This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012. [Copyright &y& Elsevier]