Risk factors of breast cancer and breast self-examination in early detection: systematic review of awareness among Indian women in community and health care professionals.

BACKGROUND: This review aims at evaluating the awareness of risk factors for breast cancer (BC) and the knowledge of breast self-examination (BSE) among Indian women and health care professionals (HCPs). METHODS: Literature search was conducted on multiple bibliographic databases with restrictions applied to English peer-reviewed journals. RESULTS: We reviewed 37 published articles on this topic. The mean level of awareness for risk factors such as age at menarche (22.3%), age at menopause (27.1%) and late first pregnancy (34.6%) was low in community. The awareness was better among HCPs; however, there was still room for improvement.Knowledge of BSE varied from very poor (2%) to good (69.8%) in the community setting. The practice was similarly negligible (0%) to moderate (34.9%). Mean knowledge and practice of BSE in HCPs were 77.1 and 55.5%, respectively. A significant difference was noted in knowledge and practice of BSE between community and HCPs (P < 0.05). CONCLUSIONS: The present review highlights the low level of awareness regarding risk factors for BC and BSE in the community as well as HCPs. Though BSE is not the ideal modality, this seems to be the best alternative for resource-limited settings.

A comparative study of cervical cancer screening methods in a rural community setting of North India.

CONTEXT: Pap smear testing as a conventional cervical screening approach has limitations for implementation and aided visual cervical testing has varying results in different regions. AIMS: The aim of this study is to demonstrate the performance of aided visual cervical screening tests as against conventional Pap smear testing in a rural community setting of North India. SETTINGS AND DESIGN: This was a rural community based cross-sectional study. MATERIALS AND METHODS: All 7603 ever married women of age 30-59 years surveyed in a pocket of Dadri Tehsil, Uttar Pradesh, India were targeted for screening by Pap, visual inspection of cervix using acetic acid (VIA) and visual inspection of cervix using Lugol's iodine (VILI) methods. Screen positives were referred to colposcopy and confirmation by histology. STATISTICAL ANALYSIS USED: Detection of histological cervical intraepithelial neoplasia (CIN) II + and CIN III + assessed separately by sensitivity, specificity and likelihood ratio's and predictive values. Analysis of data was performed by using IBM SPSS statstics software version 16.0. RESULTS: A total of 65.6%(4988/7604) eligible women of 30-59 years age group in the target population were screened. Out of 4988, further analysis was performed on 4148 after excluding those who did not complete all screenings, who lost to follow-up and had missing histology results. Screen positivity rates by Pap (ASCUS and above), VIA and VILI were 2.6%, 9.7% and 13.5% respectively. Sensitivity and specificity of detecting the CIN III+ lesions were 87.5 and 98.8% for Pap, 50.0% and 96.7% for VIA and 50.0% and 95.7% for VILI respectively. CONCLUSIONS: VIA screening demonstrated as a feasible primary screening test for detecting high grade CIN and as to perform better when the Pap test is not feasible.

CareHPV cervical cancer screening demonstration in a rural population of north India.

OBJECTIVE: To compare cervical careHPV screening in a rural community setting with other methods of cervical screening for the detection of high-grade cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. All ever-married women aged 30-59 years surveyed in an administrative area of Uttar Pradesh, India were targeted for screening by careHPV (cervical and vaginal samples), Pap test and visual inspection of the cervix following application of acetic acid (VIA). Women who screened positive were referred for colposcopy and the results were confirmed histologically. Sensitivity, specificity and predictive values for the detection of histological CINII+ and CINIII+ were assessed for each screening test. RESULTS: Sixty-five percent (5032/7704) of the women invited for cervical screening agreed to participate in the study. Screen-positive rates for cervical careHPV, vaginal careHPV, Pap test and VIA were 3%, 2%, 3% and 6%, respectively. Data for women who did not complete all screening modes, women lost to follow-up and women with missing histological results were excluded before data analysis, resulting in a final sample size of 4658. Cervical careHPV had high sensitivity (85%) for the detection of CINIII+ lesions and moderate sensitivity (53%) for the detection of CINII+ lesions. Sensitivities for the detection of CINIII+ and CINII+ were 54% and 41% for vaginal careHPV, 62% and 44% for Pap test, and 8% and 22% for VIA, respectively. CONCLUSION: Cervical careHPV testing is superior to VIA and Pap test for the detection of high-grade CIN in a rural community setting.

Modified Papanicolaou staining protocol with minimum alcohol use: a cost-cutting measure for resource-limited settings.

OBJECTIVE: To devise a simple, cost-effective protocol for Papanicolaou (Pap) staining of cervicovaginal smears. METHODS: Five hundred coded paired cervical smears were collected from women as part of routine cervical cancer screening. One set of smears was stained by conventional Pap staining protocol (CP) and the other by a modified protocol (MP) in which alcohol was replaced by 1% acetic acid in all the steps except during fixation and prior to mounting; in addition, one alcohol-based counterstain, OG, was omitted. The smears were examined blindly by the pathologists and then decoded. Each pair of smears was compared and the two protocols were analysed for staining quality and diagnoses by McNemar and chi-square tests. RESULTS: The staining quality in the MP was satisfactory. The nuclear and cytoplasmic features were comparable to the CP. Cytoplasmic transparency was maintained in the MP and the differential staining of blue/green and pink was acceptable to the pathologists and technicians. The diagnoses agreed in all cases and there was no compromise in interpreting the smears. With MP it took only 3-4 minutes to stain a batch of 50 slides. in contrast to the 20 minutes taken by CP. The MP used almost one-seventh of the amount of alcohol compared with CP, which translated into a significant cost reduction per smear. CONCLUSIONS: The improvised Pap staining protocol with minimum alcohol use is a simple, cost-effective and technician-friendly procedure that can be easily adopted in high-volume, resource-limited laboratories for mass cervical cancer screening.

Urine HPV-DNA detection for cervical cancer screening: prospects and prejudices.

Oncogenic types of human papilloma viruses (HPVs) have been established to be the causative agents for cervical cancers and high-grade squamous intraepithelial lesions (HSILs). The clinical application of molecular tests for HPV detection for screening purposes has been of considerable interest. DNA amplification methods allow the use of self-collected samples (including urine) from material collected away from the original disease site. For screening of cervical pathology, detection of HPV-DNA in urine would be useful only if it represents cervical HPV infection and/or HPV-related cervical pathology. We conducted a review of the literature in order to ascertain: (1) if urine is an adequate sample for HPV-detection; (2) whether sensitive techniques are available for HPV-detection in urine and (3) if detection of HPV in urine truly represents cervical infection/pathology. The review process consisted of assembling facts and analysing the published literature on the following facts: anatomical considerations of the lower genital and the lower urinary tract, biological behaviour of HPV and its shedding behaviour, technical issues regarding sample collection, processing and HPV-DNA assay systems, concordance rates of HPV-DNA detection and their type specificity in the paired samples (urine and cervical scrapes) obtained in different clinico-epidemiological settings and comparative detection rates of HSILs in the paired samples.

An epidemiological study to identify the risk factors with two different types of controls in high-grade cervical lesions including invasive cancer.

A multidisciplinary study on pre-cancerous and early cancerous lesions of uterine cervix was carried out at our Institute from which the subjects (cases and one group of control) for the present study were selected with the objective to identify the possible risk factors related to high-grade cervical lesions including invasive cancer through an epidemiological study by selecting two different types of controls and to assess the feasibility whether the cancers of other organs could be taken as controls at the same time studying the risk factors associated with cervical cancer. One group of control was women with negative Pap smear and second group of control was the women with breast cancer but negative Pap smear. A total of 100 biopsy-proven cases of high-grade cervical intraepithelial lesions and Invasive cancer were recruited. The results of the study show that some of the risk factors associated with the cervical cancer get exaggerated when breast cancer cases were used as controls because risk factors of both cancers are opposite to each other. So it is concluded that in order to remove any bias, normal hospital controls or controls selected from multiple cancers should be taken to study the risk factors involved in cervical carcinogenesis.

Prevalence of high-risk human papillomavirus type 16/18 infection among women with normal cytology: risk factor analysis and implications for screening and prophylaxis.

OBJECTIVE: To determine the prevalence of high-risk human papillomavirus (HR-HPV) 16/18 infection of uterine cervix among women in the reproductive age group, with cytologically normal cervical (Pap) smears; to analyse the risk factors for HR-HPV acquisition and to address their implications for cervical cancer screening and prophylaxis in a low resource setting. METHODS: Cervical samples from 769 cytologically negative women (age 18-45 years) attending a tertiary care centre in Delhi were subjected to HPV DNA testing and HR-HPV 16/18 and low-risk (LR)-HPV 6/11 sub-typing by polymerase chain reaction. Univariate risk factor analysis was carried out in HR-HPV positive (n = 86) versus HR-HPV negative women (n = 683) by chi-square test. RESULTS: The overall HPV prevalence among cytologically normal women was 16.6%. HR-HPV16 was detected in 10.1%, whereas HPV18 was detected in 1% of women. HR-HPV 16/18 comprised 67% of the total HPV positives. There was no decline in HR-HPV positivity with age, and women aged 40-44 years were at significantly increased risk for HR-HPV prevalence (P = 0.03). Statistically significant associations of HR-HPV infection were found with risk factors such as high parity (P = 0.04), cervicitis/hypertrophic cervix (P = 0.01), unhealthy cervix (P = 0.04), rural residence (P = 0.03), low socioeconomic status (P = 0.01) and illiteracy (P = 0.07). CONCLUSIONS: Although the sample size was small, based on the observation that HR-HPV 16 and 18 contributed significantly to the overall HPV prevalence in our setting, we speculate that testing/prophylaxis for these prevalent high-risk types could perhaps make cervical cancer screening and preventive programmes cost-effective. Larger community-based studies on HPV prevalence and persistence are required to validate these findings before definitive recommendations can be made to the policy makers.

Age trends in pre-cancerous and cancerous lesions of the uterine cervix in a cytology screening programme: what should be the target age group for a major thrust of screening in resource-limited settings?

OBJECTIVE: To identify the target age group where screening efforts may be concentrated in order to reduce the incidence of cervical cancer in resource-limited countries. STUDY DESIGN: The results of cyto-screening in a hospital-based screening programme for early detection of cervical cancer were analysed retrospectively. The frequency of epithelial cell abnormalities (ECAs) was computed in different age groups. OBSERVATIONS AND RESULTS: A total of 5.6% ECAs were detected on cyto-screening. The peak age incidence for squamous intraepithelial lesions (SILs) was in the 30-39 age group while that for malignancies was age >60 years. The mean ages for LSIL, HSIL and cancer were 34.7, 37.7 and 51.8 years respectively. Around 43% LSILs and 48% HSILs presented in the fourth decade. If both fourth and fifth decade are covered by screening we could detect almost two-thirds of SILs. CONCLUSIONS: A distinct latent period of more than a decade between the onset of SIL and development of frank cancer provides us with ample opportunity to prevent cervical cancer through screening. Our data validate the WHO recommendation of once in a lifetime screening of women in their fourth decade, for low-resource settings. If resources permit, screening can be extended to include women in the fifth decade. This approach would enable us to pick up maximum SILs within the available resources and prevent their progression to cancer.

Cell block as an adjunct to conventional Papanicolaou smear for diagnosis of cervical cancer in resource-limited settings.

OBJECTIVE: To assess the utility of indigenously prepared cell blocks (CBs) as an adjunct to a conventional smear test in providing a reliable diagnosis of clinically suspicious cervical cancer in resource-limited settings. METHODS: Eighty-six clinically suspicious cervical cancer cases underwent a conventional smear test, CB preparation from residual cellular samples and biopsies at the same sitting. Correlations were performed between these modalities in order to derive the sensitivity and specificity of the CB technique to diagnose cervical cancer. OBSERVATION & RESULTS: Out of 86 clinically suspicious cervical cancers, 72 (83.7%), 70 (81.4%) and 67 (77.9%) cases were diagnosed as malignant on tissue biopsies, CBs and smears respectively. CB-biopsy agreement in the diagnosis of malignancy was feasible in 87.5% of the cases while CB-Pap smear agreement was feasible in 92.5% of the cases. Sensitivity and specificity of CB preparation to diagnose malignancy was 92.5% and 100%, respectively, when the smear was taken as the reference test (excluding the unsatisfactory smears). When biopsy was taken as the gold standard, the sensitivity and specificity of CBs were 87.5% and 100% respectively (excluding the unsatisfactory biopsies). In 8/19 cases where the smear diagnoses were either unsatisfactory or atypical squamous cells/atypical glandular cells, CBs picked up malignant lesions. CONCLUSION: CBs prepared from the residual cellular sample of conventional cervical scrapes augment the sensitivity of the smear test. When used as an adjunct to the smear, CBs aid in providing a reliable diagnosis of cervical cancer in the majority of the clinically suspected cases and thus the biopsy load can be reduced significantly in resource-poor settings.

Test characteristics of various screening modalities for cervical cancer: a feasibility study to develop an alternative strategy for resource-limited settings.

OBJECTIVE: To determine test characteristics - sensitivity, specificity, positive and negative predictive values - of different screening modalities to detect cervical precancerous and cancerous lesions in order to devise an effective alternative strategy for cervical cancer screening in resource-poor settings. METHODS: A total of 472 women presenting with nonspecific gynecologic symptoms were screened by cytology, visual inspection with acetic acid application (VIA), VIA with magnification (VIAM) and human papillomavirus (HPV)-DNA testing. Colposcopic examination was performed in all and on-site biopsy was taken if any grade I and above lesion was detected on colposcopy (230). On histopathological examination, 105 showed cervical intraepithelial neoplasia II and above lesions. Sensitivity, specificity and predictive values for each test were calculated taking colposcopy and or directed biopsy as the gold standard. Comparisons were made with cytology in order to assess the feasibility of alternative strategies in resource-poor settings. RESULTS: VIA was less sensitive (86.7% versus 91.4%) but more specific (90.7% versus 86.6%) than cytology at low grade squamous intraepithelial lesion (LSIL) threshold but the difference was not statistically significant (P > 0.01). HPV testing improved the sensitivity over cytology (97.1% versus 91.4%) but there was a nonsignificant loss of specificity (84.2% versus 86.6%). Results of VIAM were more or less similar to VIA. CONCLUSION: VIA can be used as a mass screening tool for cervical cancer in resource-poor settings.

Why is high grade squamous intraepithelial neoplasia under-diagnosed on cytology in a quarter of cases? Analysis of smear characteristics in discrepant cases.

BACKGROUND: The accuracy of cervical cytology has been questioned due to high false negative rate. In order to improve the sensitivity of cytology it is prudent to analyze the factors which hamper with the diagnosis of high grade lesions. AIMS: To study the cyto-histologic agreement in High grade squamous intraepithelial lesions (HSIL) of uterine cervix and to analyze the smear characteristics in discrepant cases. SETTINGS AND DESIGN: Cervical smears of 100 histology proven cases of Cervical intraepithelial neoplasia III (CIN III) were retrieved and reviewed to study cyto-histologic agreement in the diagnosis of high grade lesions. The discrepant smears, undercalled on cytology, were further analyzed to determine the reasons for misinterpretations. Statistical analysis was performed to find out any significant factors for discrepancies. RESULTS: Cytology was able to correctly identify 74 HSILs while in 26 cases a diagnosis of Low grade squamous intraepithelial lesions (LSIL) or below was given. On review, 16 of these non correlating cases could be reclassified as HSIL on cytology while in 10 the diagnosis of LSIL or less persisted. 12/16 (75%) discrepant cases, reclassified as HSIL represented interpretive errors. Sampling errors (7/10) and air drying (5/10) were more frequent in under diagnosed cases. The statistical analysis did not yield any significant differences in the two review groups. CONCLUSION: 26% of HSIL cases were underdiagnosed on cervical smears. The major confounding factors responsible for under interpretation on cytology included air drying artifacts and metaplastic maturation of abnormal cells.

Community based study on sero-prevalence of syphilis in New Delhi (India).

Syphilis continues to be a major health problem in India. Data regarding sero-prevalence of syphilis is largely hospital based. Majority of community based studies have been conducted on select groups. Therefore, these studies do not reflect the true prevalence of syphilis in general population. The objective of the study was to determine the sero-prevalence of syphilis in the urban and rural communities of New Delhi, using both VDRL and TPHA for screening and FTA-ABS for confirmation and discrepant analysis. Serum specimens from 178 males and 227 females aged between 15-49 years were tested. VDRL test was put up using VDRL antigen from serologist, Kolkata. TPHA and FTA-ABS were performed using commercially available kits. 6.91% (28/405) subjects were found to be seropositive for syphilis (males 10.11%, females 4.40%). Syphilis seropositivity was found to be significantly associated with low income (p=0.02) and presence of symptoms suggestive of STIs (p=0.00) among males. Positive syphilis serology was significantly associated with trichomoniasis in females (p=0.00). Community based studies utilizing one non-treponemal test plus one treponemal test for screening purpose and an additional specific test for confirmation should be used for designing a control programme.

Primary malignant melanoma of uterine cervix: a rare entity diagnosed on fine needle aspiration cytology--report of a case.

Primary malignant melanoma of uterine cervix is a rare neoplasm. Its diagnosis on cervical fine needle aspiration cytology, a first of its kind in the literature, has been reported. Although cervix is a rare site for melanoma, cytopathologists should be familiar with it and be able to diagnose this entity on cervical cytology when pigment containing tumour cells are present. In a patient with visible growth on cervix, fine needle aspiration cytology may prove to be a useful diagnostic tool, especially when cervical smear/scrape cytology is non-diagnostic.

Atypical squamous cells of undetermined significance: is it worthwhile to qualify them further?

BACKGROUND: In Bethesda System of reporting cervico-vaginal smears, the equivocal epithelial cell abnormalities have been categorised as "atypical squamous and glandular cells of undetermined significance" (ASCUS and AGUS). These abnormalities may harbour minor lesions attributed to mere inflammatory changes to potentially serious high grade lesions. It is recommended to further qualify these lesions according to whether they favor a reactive or a neoplastic outcome. AIMS: We undertook the present study to assess the significance of ASCUS qualifiers. MATERIAL AND METHODS: A total of 12071 women were screened for early detection of cancer cervix. The women with ASCUS diagnosis were further qualified as ASCUS favor reactive and ASCUS favor SIL (Squamous intraepithelial lesion) according the Bethesda 1991 system of reporting. ASCUS-reactive cases were followed up by a repeat smear examination and persistent ASCUS cases were taken up for colposcopy and biopsy if indicated. All ASCUS-SIL cases were taken up for immediate colposcopy. RESULTS: The pick up rate of high grade lesions was not significantly different (P=0.47; Chi square test) on the follow up of ASCUS-reactive (2/222) and ASCUS-SIL (2/130) groups. The low grade lesions were picked up in 10/222 ASCUS-reactive and 58/130 in ASCUS-SIL, which was statistically significant (P < 0.001). CONCLUSIONS: The results of our study indicate that it is not worthwhile to qualify these lesions as majority of ASCUS-SIL also revealed only low grade epithelial which have a benign biological behaviour.

Cytomorphology of filariasis revisited. Expansion of the morphologic spectrum and coexistence with other lesions.

OBJECTIVE: To review the cytomorphologic spectrum of the filarial worm and associated tissue response in 33 cases. STUDY DESIGN: Retrospective analysis was carried out in clinically unsuspected cases of filariasis diagnosed on cytology over a period of 10 years. Twenty-nine aspirate smears from 28 patients were air dried and stained with May-Grünwald-Giemsa stain. Four routine cervical smears and one centrifuged smear of urine were stained with Papanicolaou stain. RESULTS: Microfilariae alone and along with adult gravid females were present in 25 and 4 cases, respectively. In one case both adult male and female worms with microfilariae and eggs were seen. The diagnosis was based on the presence of eggs alone in one case and fragments of female worms in two. Four of these cases were neoplastic lesions, and microfilariae were found incidentally. In one case of splenomegaly microfilariae were seen along with Leishman-Donovan bodies. CONCLUSION: Filariasis can be diagnosed on cytology by demonstrating microfilariae, a male or female worm, or eggs alone. It can be seen in association with neoplastic lesions and rarely with other parasitic infections.

Microfilariae in association with neoplastic lesions: report of five cases.

Microfilariae and adult filarial worms have occasionally been detected in association with neoplastic lesions in cytological smears. The presence of microfilariae along with neoplasms is generally regarded as a chance association, yet some authors suggest that such parasitic infestations may be a causative factor for tumourigenesis. There are only a few reported cases in cytology literature documenting this association. We report the presence of microfilariae in routine cytology smears from one benign and four malignant tumours. Microfilariae could not be identified on histopathology available in four of these cases.

Early detection of cervical cancer through acetic acid application--an aided visual inspection.

OBJECTIVE: To assess the sensitivity and specificity of visual inspection of cervix for detection of precancerous and early cancerous lesions of cervix. METHODS: In a Maternal and Child Health Care setting of New Delhi women underwent a detailed pelvic examination, visual inspection of cervix after 5% acetic acid application, cytology (pap smear), detailed colposcopic examination and colposcopic directed biopsy when indicated. RESULTS: Findings of aided visual inspection using 5% acetic acid and of cytology were evaluated among symptomatic 402 women against colposcopic findings and/or histologic reports. Seventy-three mild dysplasias, 50 moderate dysplasias, 45 severe dysplasias/Carcinoma in-situ and 40 early invasive cancerous cases were diagnosed histologically. The sensitivity of cytology (75.3%) was higher compared to that of acetic acid application (52.0%) for mild dysplasias. On the other hand, the sensitivity for detecting moderate dysplasias was 78% for cytology and 81.6% for acetic acid; for severe dysplasias/carcinoma in-situ it was 73.3% for cytology and 86.7% for acetic acid. For invasive cancers sensitivity for acetic acid application and cytology (95% for both modalities) was comparable. The specificity of cytology (99%) was higher compared to that of acetic acid application (94.3%). The false positive rate for cytology was 1.0% as against 5.7% for acetic acid application. The results of acetic acid application also showed a remarkable improvement in the sensitivity of unaided visual inspection for early cancerous lesion which was about 60% for early cancerous lesion and only 12% for mild dysplastic and 20% for moderate and severe dysplastic lesions in our earlier experience. It also reduced the false positive rates from 12% by unaided visual inspection to 5.7% by acetic acid application. Furthermore, cost of detection of one true lesion through acetic acid application (Rs.1689.00) was much lower as compared to the cost involved in cytology detected true lesions (Rs.2227.00). Visual inspection without acetic acid incurred Rs.6608.60 for detection of true lesion. CONCLUSION: Screening for cervical precancerous and cancerous lesions using visual inspection aided by acetic acid may be a suitable low-cost and a feasible alternative modality for control of cervical cancer in a resource poor setting.

Low-cost technology for screening uterine cervical cancer.

We report on an illuminated, low-cost (Rs 1500 (US$ 36)) magnifying device (Magnivisualizer) for detecting precancerous lesions of the uterine cervix. A total of 403 women attending a maternal and child health care clinic who had abnormal vaginal discharge and related symptoms were referred for detailed pelvic examination and visual inspection by means of the device after the application of 5% (v/v) acetic acid. Pap smears were obtained at the same time. The results were compared with those obtained using colposcopy and/or histology. The Magnivisualizer improved the detection rate of early cancerous lesions from 60%, for unaided visual inspection, to 95%. It also permitted detection of 58% of cases of low-grade dysplasia and 83% of cases of high-grade dysplasia; none of these cases were detectable by unaided visual inspection. For low-grade dysplasia the sensitivity of detection by means of the Magnivisualizer was 57.5%, in contrast with 75.3% for cytological examination. However, the two methodologies had similar sensitivities for higher grades of lesions. The specificity of screening with the Magnivisualizer was 94.3%, while that of cytology was 99%. The cost per screening was approximately US$ 0.55 for the Magnivisualizer and US$ 1.10 for cytology.

Nuclear grooves in intermediate cells in cervical smears.

One thousand cervical smears from women who took part in a hospital-based screening programme for early detection of cervical cancer were studied for the presence of nuclear grooves. Grooved nuclei were frequently detected in intermediate cells in all phases of the menstrual cycle, although their frequency of occurrence was slightly lower in the luteal and premenstrual phases. The mean number of nuclear grooves varied from 3.6 to 4.2 in different phases of the menstrual cycle. The differences, however, were not statistically significant. The presence of nuclear grooves in cervical cells appears to be a nonspecific finding at present.