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.

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.

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.

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.

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.