Two-dose recommendation for Human Papillomavirus vaccine can be extended up to 18 years - updated evidence from Indian follow-up cohort study.

Earlier publication from the ongoing multi-centric study of the International Agency for Research on Cancer to evaluate less than three doses of the quadrivalent Human Papillomavirus (HPV) vaccine in India amongst unmarried girls demonstrated non-inferior total antibody titres, neutralizing antibody titres and antibody avidity in 2-dose recipients compared to 3-dose recipients at 15-18 years of age (Bhatla et al., 2018) [7]. The number of participants recruited at 15-18 years of age was 1515 and 1795 in the 3-dose and the 2-dose groups respectively. At a median follow-up of 7 years, incident HPV 16/18 infections were detected in 1.6% women receiving two doses and 0.8% women receiving three doses at 15-18 years. Frequency of incident infection was 7.0% in the age- and site-matched unvaccinated women (N = 1484). No persistent infection from HPV 16 was observed in the 2- or 3-dose recipients and one (0.2%) persistent HPV 18 infection was documented, each in the 3-dose and 2-dose cohorts. Among the unvaccinated women, the frequency of HPV 16/18 persistent infection was 1.7%. The protection offered by two doses of quadrivalent HPV vaccine against incident and persistent infections in recipients at 15-18 years is comparable to that seen in 3-dose recipients at 15-18 years.

Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western India.

Breast cancer is an emerging public health problem in low- and middle-income countries. The main objective is to describe the clinical characteristics and patterns of care of breast cancer patients diagnosed and treated in a rural cancer hospital in Barshi, Western India. The results from a cross-sectional study of 99 consecutive breast cancer patients diagnosed and treated between February 2012 and November 2014 in Nargis Dutt Memorial Cancer Hospital is reported. The case records of the patients were scrutinized and reviewed to abstract data on their clinical characteristics, diagnostic, and treatment details. The mean age at diagnosis of the patients was 52.8 ± 11.6 years; 83.5% of women were married, and 60.6% were illiterate. Sixty percent of patients had tumors measuring 5 cm or less. Almost half of the patients (46.4%) had stage I or II A disease and a third (36.0%) had axillary lymph node metastasis. Estrogen, progesterone, and human epidermal growth factor receptor2 receptor status were investigated in 41 (41.4%) of patients only. The median interval between diagnosis and initiation of treatment was 11 days. Modified radical mastectomy was done in 91% of patients, and nearly a third of patients who were prescribed chemotherapy did not complete treatment. The rural-based tertiary cancer care center has made treatment more accessible to breast cancer patients and has reduced the interval between diagnosis and treatment initiation. However, there are still many challenges like non-compliance to and incomplete treatments and poor follow-up that need to be addressed.

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

BACKGROUND: Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. METHODS: In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. FINDINGS: Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. CONCLUSION: Our results indicate that a single dose of quadrivalent HPV vaccine is immunogenic and provides lasting protection against HPV 16 and 18 infections similar to the three- and two-dose vaccine schedules, although the study suffer from some limitations. Data on long term protection beyond 7 years against HPV infection and cervical precancerous lesions are needed before policy guidelines regarding a single dose can be formulated and implemented. Significant and long-lasting protective effect of a single dose can be a strong argument to introduce one dose of the HPV vaccine in many low income countries where the current standard of care for cervical cancer prevention is 'no intervention'.

Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India.

Extending two-dose recommendations of HPV vaccine to girls between 15 and 18 years will reduce program cost and improve compliance. Immunogenicity and vaccine targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180 days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N = 3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1-binding antibody titres at seven months against vaccine-targeted HPV types compared to three-dose recipients at 15-18 years and three-dose recipients at 10-14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two-dose recipients were non-inferior to same age three-dose recipients for all except HPV 18. The titres were inferior to those in the 10-14 year old three-dose recipients for all targeted types. Frequency of incident infections from vaccine-targeted HPV types in the 15-18 year old two-dose recipients was similar to the three dose recipients. None of the girls receiving two or three doses had persistent infection from vaccine-targeted types. These findings support that two doses of HPV vaccine can be extended to girls aged 15-18 years.

Improved Survival of Cervical Cancer Patients in a Screened Population in Rural India

Objectives: To describe the survival experience of cervix cancer patients in a screened rural population in India. Methods: Included 558 cervical cancer patients diagnosed in 2000-2013 in a cohort of 100,258 women invited for screening during 2000-2003. The primary end point was death from cervical cancer. We used the Kaplan-Meier method to estimate cumulative observed survival and Cox proportional hazards regression to assess the effect of patient characteristics on survival after diagnosis. Results: Of the 558 cases included, 143 (26%) and 114 (20%) were diagnosed in stages IA and IB respectively; 252 (45.2%) were dead, and 306 (54.8%) were alive at the last follow-up. The overall 5-year observed survival was 60.5%. The 5-year survival of stage IA patients was 95.1% and 5.3% for stage IV patients. All surgically treated stage IA patients, 94.1% of stage IB patients receiving intracavitary radiotherapy, 62% of stage IIB, 49% of stage III and 25% of stage IV patients receiving radiotherapy survived for 5 years. Conclusion: Higher 5-year survival in our study than elsewhere in India is due to the high proportion of early stage cancers detected by screening combined with adequate treatment, resulting into a favourable prognosis.

Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study.

BACKGROUND: An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study. METHODS: Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10-18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. FINDINGS: Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02-1·23] and for HPV 18 1·04 [0·92-1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29-0·38] for HPV 16 and 0·51 [0·43-0·59] for HPV 18) and one-dose default (0·09 [0·08-0·11] for HPV 16 and 0·12 [0·10-0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2-5·1). INTERPRETATION: Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment. FUNDING: Bill & Melinda Gates Foundation.

Response to article titled "US-funded measurements of cervical cancer death rates in India: scientific and ethical concerns" by Eric J Suba.

Dr Eric Suba has been distorting facts and persistently disseminating biased and misleading views and statements regarding our studies over the past several years. His article in the Indian Journal of Medical Ethics fails to mention the facts that seem unfavourable to his arguments, and the ethical concerns are unsubstantiated by the evidence. In this context, we present the following clarifications for the attention of your readers, notably with regard to: (i) the study design and inclusion of a control group; (ii) the informed consent of the women participating in the study; (iii) the conformity with international ethical standards and guidelines, and (iv) the provision of screening to women in the control arm of the studies. We also highlight the benefits that are flowing from this research and the risk that misinformation may further delay access for women to life-saving cervical cancer screening.

Evaluation of cytology and visual triage of human papillomavirus-positive women in cervical cancer prevention in India.

Although virtually all cervical cancers and most cervical intraepithelial neoplasia (CIN) are caused by persistent human papillomavirus (HPV) infection, only a small proportion of HPV-positive women have or will develop CIN. Triaging HPV-positive women has been suggested to reduce the false-positive rate and proportion of women referred for CIN confirmation and/or treatment. In two cross-sectional studies and one randomized trial in India, we evaluated the impact of using cytology or visual inspection with acetic acid (VIA) to triage HPV-positive women on the proportion of women who would be referred for CIN confirmation and on the detection rates of high-grade CIN. We present the numbers of HPV test-positive women found and the CIN detected among them. We further assess the proportions that would be referred for CIN confirmation with colposcopy/biopsy and CIN that would be detected if cytology triage or VIA triage were used. Using cytology triage at atypical squamous cells of undetermined significance threshold or VIA triage reduced referrals for colposcopy by about 62% and 59%, respectively (p-value = 0.012), but missed around 16% and 18%, respectively, of the high-grade CIN (p-value = 0.539) indicating similar performance of both triaging approaches. The choice of a triage test in different low- and middle-income countries (LMIC) would depend on the availability and affordability in the particular setting. Cytology triage may be considered in settings where adequate infrastructure exists, whereas VIA triage may be suitable in settings with limited or no cytology infrastructure.

Accuracy of concurrent visual and cytology screening in detecting cervical cancer precursors in rural India.

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called "Screening Technologies to Advance Rapid Testing" in 5,519 women aged 30-49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high-risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high-grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high-grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow-up when women must be recalled following positive cytology. Organizing visual screening services in low-resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future.

Prevalence of human papillomavirus types in cervical lesions from women in rural Western India.

Cervical cancer is the most common cancer among women in many areas of India which contributes for a fifth of the global burden of disease. Persistent infection with one of the high-risk human papillomaviruses (HPV) has been established as the cause for cervical cancer and the documentation of the prevalence of HPV types in cervical cancer in different regions of India is useful for a prevention program combining both screening and vaccination. In this study, the HPV type distribution and the frequency of p16(INK4a) immunoexpression have been determined in 125 cases of inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 74 cases of grade 2, 72 cases of grade 3, and 113 cervical cancer cases diagnosed among women from rural Solapur and Osmanabad districts, Maharashtra. The overall prevalence of high-risk HPV was 37.6% in inflammatory lesions or grade 1 cervical intraepithelial neoplasia, 63.5% in grade 2, 97.2% in grade 3 and 92% in cervical cancer cases. HPV 16 and HPV 18 were detected in 80.6% of grade 3 cervical intraepithelial neoplasia and 86.5% of cervical cancer cases. 94.7% of the cervical cancer and 84.4% of the high grade lesions with a strong and full thickness staining for p16(INK4a) were positive for HPV infection; p16(INK4a) immunoexpression increased with worsening grade of cervical intraepithelial neoplasia. The HPV genotyping data showing a high HPV 16 and 18 prevalence in cancer specimens indicate that prophylactic HPV 16/18 vaccination would have a significant impact on the prevention of cervical cancer in India.

Prevalence and determinants of high-risk human papillomavirus infection in middle-aged Indian women.

BACKGROUND: Little is known about the prevalence and determinants of human papillomavirus (HPV) infection in women from West India, although incidence of and mortality from cervical cancer is high. METHODS: Cervical specimens were collected, and questionnaires on lifestyle and reproductive factors were administered to 27,192 ever-married women aged 30 to 59 years living in a rural area of Maharashtra State, India. HPV-DNA status for high-risk HPV types was assessed using the second-generation hybrid-capture II assay. RESULTS: The prevalence of HPV infection was 10.3% in this population of middle-aged women. High-risk HPV infection was associated with increasing age, low education level, manual work, early age at first sexual intercourse, and widowhood or separation. CONCLUSION: Low socioeconomic status and vulnerable social groups such as widows and separated women are at a higher risk of HPV infection. This study demonstrates once again that HPV infection and subsequent cervical cancer are social diseases.

[p16INK4A overexpression is a useful marker for uterine cervix lesions]. / La surexpression de p16 INK4A est un marqueur utile des lésions du col utérin.

The histological criteria of uterine cervix lesions are well known. However, there is a poor diagnostic reproducibility especially concerning low-grade precancerous lesions. Therefore, the aim of our study was to evaluate the utility of p16INK4A overexpression as a surrogate biomarker of precancerous lesions of the uterine cervix. A retrospective study was carried out by the International Center for Research on Cancer, Lyon, on 79 uterine cervix lesions. Specimens included 4 normal tissue samples, 24 benign lesions, 9 low-grade precancerous lesions (CIN1), 40 high-grade precancerous lesions (CIN2-3) and 2 squamous cell carcinomas. Immunohistochemistry was used to find p16INK4A expression. HPV infection was detected by HPV testing. No p16INK4A expression was detected in normal tissues and benign lesions of the uterine cervix. p16INK4A immunolabeling was weak in CIN1 cases (77.8%). Strong and diffuse p16INK4A expression was detected among all precancerous lesions (CIN2-3) and squamous cell carcinomas. p16INK4A overexpression was associated to the CIN grade (p<0.0001) and high-risk HPV infection (p<0.0001). In conclusion, p16INK4A overexpression should be regarded as a surrogate biomarker of precancerous lesions of the uterine cervix. p16INK4A overexpression is useful in reducing the variability during evaluation of suspicious biopsies of the uterine cervix.

Rural cancer registry at Barshi, Maharashtra and its impact on cancer control.

BACKGROUND: The relevance of population-based cancer registries for planning and implementing cancer control programmes cannot be overemphasized. There are some urban registries in India but very few rural registries despite India being predominantly rural. There are several obstacles to setting up a rural registry including lack of cancer awareness in the rural population and inaccessibility of modern medical facilities. The first rural cancer registry was set up in 1987 at Barshi (population 0.4 million) in western Maharashtra by adopting a methodology suitable for rural areas. METHODS: The innovative methodology supplemented the usual registry methodology by regular interaction with the community to educate them on warning signals for cancer, raise cancer awareness and motivate suspected individuals to seek medical attention. Cancer detection clinics were held in villages. RESULTS: The reliability indices show that the registry is of an acceptable standard. The registry activity has increased cancer awareness in this population (p < 0.01), increased the frequency of early cervical cancers (stages I and IIa) by more than 2-fold during the past 16 years and significantly decreased the relative risk of death (hazard ratio 0.7 [0.5-0.9]). CONCLUSION: The innovative methodology has facilitated the process of cancer registration in rural areas. It has had a positive impact on cancer awareness, stage at presentation and survival of cervical cancers-the predominant cancer in the area. The registry has created a resource for epidemiological studies in a rural area where national and international studies are currently being undertaken.

Cancer survival in Africa, Asia, and Central America: a population-based study.

BACKGROUND: Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions. METHODS: Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined. FINDINGS: For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76-82% for breast cancer, 63-79% for cervical cancer, 71-78% for bladder cancer, and 44-60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services. INTERPRETATION: The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources. FUNDING: Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).

HPV screening for cervical cancer in rural India.

BACKGROUND: In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. METHODS: In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. RESULTS: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. CONCLUSIONS: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

Prevalence of tobacco use and tobacco-dependent cancers in males in the Rural Cancer Registry population at Barshi, India.

BACKGROUND: In the Rural Cancer Registry at Barshi (western Maharashtra, India), it has been found that the incidence of cancer is relatively low. AIM: To explain the low incidence of tobacco related cancers in males on the basis of prevalence of their tobacco habits. SETTING AND DESIGN: Simple random sample of villages from Barshi Rural Cancer Registry. MATERIAL AND METHODS: A tobacco survey was carried out in 5,319 adult males. Site specific incidence data for Barshi and Mumbai Cancer Registries were available from published reports in the National Cancer Registry Programme. Published report of prevalence of tobacco habits in Mumbai males was available. RESULTS: The tobacco survey showed that the prevalence of smoking compared to Mumbai was low (9.9% vs 23.6%) and the incidence of smoking dependent cancers viz., cancers of oropharynx, larynx and lung were significantly low (P< 0.05). However, although the proportion of tobacco chewers is higher in Barshi compared to Mumbai, the incidence rates for cancer of hypopharynx and oral cancer which are predominantly chewing dependent did not show higher rate than in Mumbai. CONCLUSIONS: The low incidence of smoking dependent cancers in males can be explained by the low prevalence of smoking habit but further studies are needed to explain the observed incidence of predominantly chewing dependent cancers.

Human papillomavirus infection and cervical cancer prevention in India, Bangladesh, Sri Lanka and Nepal.

Although one-third of the world cervical cancer burden is endured in India, Bangladesh, Nepal and Sri Lanka, there are important gaps in our knowledge of the distribution and determinants of the disease in addition to inadequate investments in screening, diagnosis and treatment in these countries. Prevalence of human papillomavirus (HPV) infection among the general populations varies from 7-14% and the age-specific prevalence across age groups is constant with no clear peak in young women. This observation may be the result of a low clearance rate of incident infections, frequent re-infection/reactivation, limited or no data in target high-risk age groups (teenagers), and sexual behavioural patterns in the population. High-risk HPV types were found in 97% of cervical cancers, and HPV-16 and 18 were found in 80% of cancers in India. Beyond research studies, demonstration projects and provincial efforts in selected districts, there are no serious initiatives to introduce population-based screening by public health authorities in these countries. Cervical cancer is a relatively neglected disease in terms of advocacy, screening and prevention from professional or public health organizations. Cytology, HPV testing and visual screening with acetic acid (VIA) or Lugol's iodine (VILI) are known to be accurate and effective methods to detect cervical cancer and could contribute to the reduction of disease in these countries. While HPV vaccination provides hope for the future, several barriers prohibit the introduction of prophylactic vaccines in these countries such as high costs and low public awareness of cervical cancer. Efforts to implement screening based on the research experiences in the region offer the only currently viable means of rapidly reducing the heavy burden of disease.

Effectiveness, safety, and acceptability of cryotherapy by midwives for cervical intraepithelial neoplasia in Maharashtra, India.

OBJECTIVE: To evaluate the effectiveness, safety, and acceptability of cryotherapy for cervical intraepithelial neoplasia (CIN) when provided by trained midwives in rural India. METHOD: Women with colposcopic findings of CIN lesions suitable for ablative treatment received cryotherapy from trained midwives before the biopsy results were known. Cure rates, adverse effects, and complications were assessed and factors influencing cure rates were evaluated by chi(2) tests. Cure was defined as no clinical or histologic evidence of CIN lesions 6 or more months after treatment. RESULTS: Of 1068 women treated with cryotherapy, 728 had histologically proven CIN in their pretreatment biopsy specimens; of the 574 reporting for follow-up, 538 (93.7%) were cured (95% confidence interval [CI], 92.1%-96.3%). Cure rates were 96.4% (95% CI, 94.6%-98.1%) for CIN 1 and 82.1% (95% CI, 74.7%-89.4%) for CIN 2 and CIN 3 lesions combined. Minor adverse effects were documented in 5.2% of the women. CONCLUSION: Cryotherapy provided by midwives was found to be safe, effective, and acceptable by the women.

Determinants of womens participation in cervical cancer screening trial, Maharashtra, India.

OBJECTIVE: To determine the factors associated with participation in cervical cancer screening and follow-up treatment in the context of a randomized controlled trial. The trial was initiated to evaluate the efficacy and cost effectiveness of visual inspection with acetic acid, cytological screening and testing for human papillomavirus in reducing the incidence of and mortality from cervical cancer in Maharashtra, India. METHODS: Between October 1999 and November 2003 women aged 30-59 years were randomized to receive one of the three tests or to a control group. Participation was analysed for all three intervention arms. The differences between those who were screened versus those who were not was analysed according to the sociodemographic characteristics of the 100,800 eligible women invited for screening. Those who were treated versus those who were not were analysed according to the sociodemographic characteristics of the 932 women diagnosed with high-grade lesions. Participation in screening and compliance with treatment were also analysed according to the type of test used. FINDINGS: Compared with women who were not tested, screened women were younger (aged 30-39), better educated and had ever used contraception. A higher proportion of screened women were married and a lower proportion had never been pregnant. Of the 932 women diagnosed with high-grade lesions or invasive cancer, 85.3% (795) received treatment. Women with higher levels of education, who had had fewer pregnancies and those who were married were more likely to comply with treatment. There were no differences in rates of screening or compliance with treatment when results were analysed by the test received. CONCLUSIONS: Irrespective of the test being used, good participation levels for cervical cancer screening can be achieved in rural areas of developing countries by using appropriate strategies to deliver services. Communication methods and delivery strategies aimed at encouraging older, less-educated women, who have less contact with reproductive services, are needed to further increase screening uptake.