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1.  Can sunspot activity and ultraviolet-B radiation explain cyclic outbreaks of forest moth pest species? 
Cyclic outbreaks of forest moth pest species have long remained a puzzle for foresters and ecologists. This paper presents time-series exhibiting a strong negative relationship between sunspot numbers and population indices of autumnal and winter moths, both in a mountain birch forest in central Norway and in a mixed lowland forest in southern Norway. In the latter area, also the population level of a moth species feeding entirely on lichens was negatively related to sunspot numbers. Low sunspot activity leads to a thinner ozone layer and thus higher surface ultraviolet (UV)-B radiation. As winter moth larvae prefer leaves subjected to enhanced UV-B radiation, we suggest that the causal relationship between sunspots and moths is that the metabolic costs of producing UV-B-protective pigments during periods of low sunspot activity reduce trees' and lichens' resistance to herbivores, and thus increase the survival of moth larvae. Higher peak densities of moth cycles in mountain forests could be explained by the general higher UV-B radiation at higher altitudes.
doi:10.1098/rspb.2004.2811
PMCID: PMC1691813  PMID: 15347511
2.  Solar activity affects avian timing of reproduction 
Biology Letters  2009;5(6):739-742.
Avian timing of reproduction is strongly affected by ambient temperature. Here we show that there is an additional effect of sunspots on laying date, from five long-term population studies of great and blue tits (Parus major and Cyanistes caeruleus), demonstrating for the first time that solar activity not only has an effect on population numbers but that it also affects the timing of animal behaviour. This effect is statistically independent of ambient temperature. In years with few sunspots, birds initiate laying late while they are often early in years with many sunspots. The sunspot effect may be owing to a crucial difference between the method of temperature measurements by meteorological stations (in the shade) and the temperatures experienced by the birds. A better understanding of the impact of all the thermal components of weather on the phenology of ecosystems is essential when predicting their responses to climate change.
doi:10.1098/rsbl.2009.0429
PMCID: PMC2827989  PMID: 19574283
timing of reproduction; sunspots; birds; Parus major; Cyanistes caeruleus
3.  Association between acute glaucoma and the weather and sunspot activity. 
The dates of presentation of 191 cases of acute closed-angle glaucoma which presented at the Birmingham and Midland Eye Hospital between 1971 and 1974 were analysed and the seasonal incidence of acute glaucoma confirmed (P less than 0-001). These data were compared with meteorological data for air temperature, rainfall, hours of sunshine, atmospheric pressure, cloud amount, terrestrial magnetic field level, and sunspot numbers. A statistically significant direct association (P less than 0-05) was found with hours of sunshine and an inverse association (P greater than 0-05) with cloud amount. A statistically significant inverse association (P less than 0-05) was found with sunspot count, and this assumed high significance (P less than 0-0005) on consideration of sunspot activity in the preceding period. The literature is reviewed and the significance of these findings discussed.
PMCID: PMC1043029  PMID: 911731
4.  Cyclic patterns of incidence rate for skin malignant melanoma: association with heliogeophysical activity*  
Background: Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma (SMM; ICD9, Dx:172) in the Czech Republic (period T=7.50~7.63 years), UK (T=11.00 years) and Bulgaria (T=12.20 years). Incidences compared with the sunspot index Rz (lag-period dT=+2, +4, +6, +10 or +12 years) have indicated that maximal rates are most likely to appear on descending slopes of the 11-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity (HGA) components exhibiting similar cyclicity. Methods: Annual incidences of SMM from 5 countries (Czech Republic, UK, Bulgaria, USA and Canada) over various time spans during the years 1964~1992 were analyzed and their correlations with cyclic Rz (sunspot number) and aa (planetary geomagnetic activity) indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results: Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA (T=8.63 years, P<0.05) and Canada (Ontario, T=9.91 years, P<0.10). Also, various ‘hypercycles’ were established (T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively) describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz (dT=+6 and +7 years, respectively) and aa (dT=−10 and +9 years, respectively) was described. Possible interactions of cyclic non-photic influences (UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations) with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion: The above findings on cyclicity and temporal association of SMM with cyclic environmental factors could not only allow for better forecasting models but also lead to a better understanding of melanoma aetiology.
doi:10.1631/jzus.B0820076
PMCID: PMC2408703  PMID: 18543403
Melanoma incidence; Cyclicity; Heliogeophysical activity (HGA); Forecasting; Skin neurobiology
5.  Human Papillomavirus Typing in HIV-Positive Women 
Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate the results to those of the Pap smear.
Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing were correlated with those of the Pap smear in a retrospective analysis.
Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for low-risk subtypes.
Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.
doi:10.1155/S1064744901000163
PMCID: PMC1784640  PMID: 11495559
6.  Pattern of epithelial cell abnormality in Pap smear: A clinicopathological and demographic correlation 
CytoJournal  2011;8:8.
Background:
In the low resource settings of a developing country, a conventional Papanicolaou (Pap) test is the mainstay screening system for cervical cancer. In order to counsel women and to organize a public health system for cervical cancer screening by Pap smear examination, it is imperative to know the pattern of premalignant and malignant lesions. This study was undertaken to find out the prevalence of an abnormal Pap smear, in a tertiary hospital of a developing country, and to carry out a clinicopathological and demographical analysis for establishing the pattern of epithelial cell abnormality in a Pap smear.
Materials and Methods:
A cross-sectional descriptive study was carried out in a total of 1699 patients who underwent Pap smear examination. The prevalence of epithelial cell abnormality in the Pap smear was calculated in proportions / percentages. Specimen adequacy and reporting was assessed according to the revised Bethesda system.
Results:
Among the total of 1699 patients who had their Pap smear done, 139 (8.18%) revealed epithelial cell abnormality. Altogether 26 smears revealed high-grade lesions and malignancy, most of which were found to be in women belonging to the 30 – 39 and ≥ 45 age group. A total of 75 (53.96%) women were in the 20 – 44 age group and 64 (46.04%) were in the ≥ 45 age group. A bimodal age distribution was detected in the epithelial cell abnormality, with the bulk being diagnosed in patients aged 45 or above. Overall one-third of the patients with an abnormal Pap smear result showed healthy cervix in per vaginal examination.
Conclusions:
A raised prevalence of epithelial cell abnormality reflects the lack of awareness about cervical cancer screening. Women aged 45 or above harbor the bulk of premalignant and malignant lesions in the Pap smear, signifying that these women are among the under users of cytological screening.
doi:10.4103/1742-6413.80527
PMCID: PMC3119384  PMID: 21713015
Cervical cancer; cytology; Papanicolaou smear
7.  Detection of abnormal cervical cytology in Papanicolaou smears 
Background:
Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions. Cervical intra-epithelial neoplasia (CIN) and cervical cancer remain important health problems for women worldwide.
Aim:
To study the role of Pap smear in detecting premalignant and malignant lesions of cervix; and to determine the prevalence of various lesions.
Materials and Methods:
This study is based on 300 patients who attended the out-patient Department of Obstetrics and Gynaecology. Pap smears were prepared from patients presenting with complaints like vaginal discharge, post-coital bleeding, inter-menstrual bleeding, dyspareunia, and pain lower abdomen. After fixation and staining, each smear was carefully examined.
Results:
Epithelial cell abnormalities were found in 5% smears, atypical squamous cells of undetermined significance (ASCUS) in 0.3%, squamous intraepithelial lesion (SIL) in 3.4% which includes low grade squamous intraepithelial lesion (LSIL) (2.7%) and high grade squamous intraepithelial lesion (HSIL) 0.7%. Invasive carcinoma was seen in 1.3% cases. Mean age of the patients with diagnosis of LSIL was 32.3 years and for HSIL, it was 40.5 years. The mean age of the patients with invasive carcinoma was 57 years.
Conclusion:
Premalignant and malignant lesions of cervix are not uncommon in our set up and can be diagnosed early by Pap smears.
doi:10.4103/0970-9371.93222
PMCID: PMC3307451  PMID: 22438616
Cervical cancer; cervical intraepithelial neoplasia; papanicolaou smear
8.  Colposcopic evaluation of cervix with persistent inflammatory Pap smear: A prospective analytical study 
CytoJournal  2010;7:16.
Background:
Inflammatory Pap smear is the most common report received by a gynecologist. The cervical screening algorithm for benign cellular changes on the Pap smear recommends treatment of infection if indicated and a repeat Pap smear in 4 to 6 months time. If the inflammatory changes still persist, subject the patient to colposcopy. However, in practice, this is not followed, especially in developing countries like ours where proper screening protocols are not available. Hence, a good number of patients in the premalignant stage are being missed. This study was undertaken to evaluate patients with persistent inflammatory Pap smears without atypia using colposcopy.
Methods:
A prospective analytical study of 150 gynecologial patients with persistent inflammatory Pap smear between 2006 and 2008 in an out-patient setting. All of them were subjected to colposcopy and biopsy from the abnormal areas. The incidence of cervical intraepithelial neoplasia (CIN)/invasive carcinoma was calculated by proportions/percentages.
Results:
The incidence of invasive carcinoma was <1%. But, the incidence of pre-malignant lesions (CIN) was high (20.9%). CIN 2/3 and carcinoma in situ were present in 6.9% of the cases.
Conclusions:
Patients with persistent inflammatory Pap smears can harbour a high proportion of CIN and hence these patients will need further evaluation.
doi:10.4103/1742-6413.67112
PMCID: PMC2926920  PMID: 20806087
Invasive carcinoma; non-specific inflammation; persistent inflammatory cellular changes; squamous intraepithelial lesion
9.  Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer. 
Journal of Clinical Pathology  1995;48(8):728-732.
AIM--To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS--Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design. RESULTS--HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens. CONCLUSIONS--The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.
PMCID: PMC502799  PMID: 7560199
10.  A pilot study to compare HIV status and cervical and penile pathology among couples attending the urology unit at the University Teaching Hospital Lusaka, Zambia 
Medical journal of Zambia  2010;37(2):84-88.
Background
Cancer of the cervix is the most common malignancy in women of childbearing age in Zambia. It is known to be associated with HIV infection and oncogenic strains of HPV. However, there are few studies of penile lesions as a predictor of malignant and premalignant cervical lesions in female partners.
Objectives
The aim of the study was to determine the association between men with penile lesions and premalignant cervical lesions in their female partners.
Design
Thirty-seven couples were screened for penile and cervical lesions to determine the association between the two. The male partners had a biopsy and the female partners had a Pap smear.
Results
Among 37 female partners, 29 (78.3%) had some type of cervical lesion. Two (5.4%) were undetermined and 6 (16.3%) of the females had normal Pap smears. Among the spouses with diseased cervices 22 (59.4%) were premalignant and 5 (13.5%) were malignant. The combined prevalence of malignant or premalignant cervical lesions among female partners was 73.0%. The HIV prevalence in the cohort was 88.9% (among those who agreed to be tested). The prevalence of premalignant or malignant cervical lesions was 75% in HIV positive and HIV negative females, and 66.7% in those who refused HIV testing.
Conclusion
This small pilot study suggests a high prevalence of premalignant or malignant lesions in females whose partners have penile lesions. In this cohort, HIV infection was not associated with a higher risk of neoplastic cervical lesions.
PMCID: PMC3591472  PMID: 23476097
11.  Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project 
Background
Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted.
Methods
The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV).
Results
EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed positivity for pan HPV in 65.9% of the studied biopsies (n = 217), with incorporation of the viral genome HPV 6/11, 16/18 and 31/33 in 11.1%, 33.3% and 17.1% respectively. Multiple HPVs infections were identified in 0.02%.
Conclusion
Pre-invasive high grade lesions and invasive cervical carcinoma represent 0.5% and 0.04% respectively in Egyptian women. HPV mostly 16/18 as a risk factor (p < 0.001), was frequently associated with mixed infections (p < 0.001) and bilharzial infestation (p < 0.001).
doi:10.1186/1750-9378-2-12
PMCID: PMC1945019  PMID: 17610742
12.  EVALUATION OF A CERVICAL CANCER LAY HEALTH WORKER INTERVENTION FOR VIETNAMESE AMERICAN WOMEN 
American journal of public health  2010;100(10):1924-1929.
Objectives
We conducted a trial to evaluate the effectiveness of a cervical cancer control intervention for Vietnamese women.
Methods
The study group included 234 women who had not received a Pap test in the last three years. Experimental group participants received a lay health worker home visit. Our trial end-point was Pap smear receipt within six months of randomization. Pap testing completion was ascertained through women's self-reports and medical record reviews. We examined intervention effects among women who had ever received a Pap smear (prior to randomization) and women who had never received a Pap smear.
Results
Three-quarters of the experimental group women completed a home visit. Ever screened experimental group women were significantly more likely to report Pap testing (p<0.02) and have records verified Pap testing (p<0.04) than ever screened control group women. There were no significant differences between the trial arms for women who had never been screened.
Conclusions
Our findings indicate that lay health worker interventions for Vietnamese women are feasible to implement and can positively impact levels of Pap testing use among ever screened women (but not never screened women).
doi:10.2105/AJPH.2009.190348
PMCID: PMC2936992  PMID: 20724673
Asian Americans; Cancer; Screening
13.  Mating success of resident versus non-resident males in a territorial butterfly 
Male–male competition over territorial ownership suggests that winning is associated with considerable benefits. In the speckled wood butterfly, Pararge aegeria, males fight over sunspot territories on the forest floor; winners gain sole residency of a sunspot, whereas losers patrol the forest in search of females. It is currently not known whether residents experience greater mating success than non-residents, or whether mating success is contingent on environmental conditions. Here we performed an experiment in which virgin females of P. aegeria were allowed to choose between a resident and a non-resident male in a large enclosure containing one territorial sunspot. Resident males achieved approximately twice as many matings as non-residents, primarily because matings were most often preceded by a female being discovered when flying through a sunspot. There was no evidence that territorial residents were more attractive per se, with females seen to reject them as often as non-residents. Furthermore, in the cases where females were discovered outside of the sunspot, they were just as likely to mate with non-residents as residents. We hypothesize that the proximate advantage of territory ownership is that light conditions in a large sunspot greatly increase the male's ability to detect and intercept passing receptive females.
doi:10.1098/rspb.2007.0311
PMCID: PMC1914333  PMID: 17472909
Lepidoptera; contest success; mate locating behaviour; female choice; mate choice; butterfly vision
14.  Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population. 
The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.
PMCID: PMC2607629  PMID: 7794301
15.  Frequency of Cervical Cancer and Breast Cancer Screening in HIV–Infected Women in a County-Based HIV Clinic in the Western United States 
Journal of Women's Health  2010;19(4):709-712.
Abstract
Background
Women's primary-care services are frequently dispensed to HIV-infected women through HIV specialty clinics. Our objective was to evaluate cervical cancer and breast cancer screening practices in a county-based HIV clinic in San Mateo, California.
Methods
This was a retrospective cohort study of medical records of HIV-infected women obtaining HIV care at this site.
Results
Between January 1, 2002 and December 31, 2006, 69 women were documented to have at least 12 months of medical care at the clinic. Median followup time was 51 months. Over 253 person-years of followup, there were 656 pap smears performed per 1,000 person-years; 77.9% of women had at least one Pap smear during the study time period. A total of 59.5% (47/79) of normal pap smears had a followup pap smear within 18 months; 62.0% of abnormal pap smears had a followup pap smear within 12 months. A CD4 count of less than 200 cells/mm3 was associated with not receiving a pap smear in multivariable analysis. Mammogram screening was performed on 64.7% of women aged 40 or older.
Conclusions
Based on the results of this study, the majority of HIV-infected women at this clinic received cervical and breast cancer screening at some point during their care. Only two-thirds of abnormal pap smear results had followup pap smear screening within a year. With the increased risk of cervical cancer in HIV-infected women, efforts should be made to promote cervical cancer screening, particularly in high-risk women.
doi:10.1089/jwh.2009.1412
PMCID: PMC2867552  PMID: 20201703
16.  Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study 
Background
Almost one-third of Norwegian women aged 25–69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme.
Methods
Among 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996–7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively.
Results
69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant.
Conclusion
Pap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening.
doi:10.1186/1472-6963-7-10
PMCID: PMC1790705  PMID: 17244348
17.  Collection of Cervical Secretions Does Not Adversely Affect Pap Smears Taken Immediately Afterward 
Collection of cervical secretions for local immunological assessment requires that the secretions be collected prior to the Pap smear to avoid contamination with blood. The objective of the present study was to determine whether gentle collection of cervical secretions prior to a Pap smear collection influences the quality of the Pap smear. A total of 266 women were recruited. Half of the participants were assigned to collection of cervical secretions prior to Pap smear collection with Weck-cel sponges. The remaining half had only the Pap smear collection performed. Pap smear slides were reviewed and evaluated for quality by the Bethesda System adequacy criteria without knowledge of randomization. The proportions of limited or inadequate slides in the two study groups were compared by using the Pearson chi-square test. No significant differences were observed between the two study groups when overall Pap smear quality was evaluated (P = 0.29). Comparison of the two study groups with respect to individual adequacy criteria, including presence of air drying artifact, presence of obscuring blood, absence of metaplastic or endocervical cells from the transformation zone, scant cellularity, and presence of obscuring inflammatory cells, also revealed no significant differences between the two study groups. Results from the present study suggest that the collection of cervical secretions with Weck-cel sponges does not adversely impact the quality of subsequently obtained Pap smears.
PMCID: PMC95605  PMID: 9665954
18.  Prevalence of human papilloma virus in cytological abnormalities: Association of risk factors and cytomorphological findings 
CytoJournal  2012;9:19.
Background:
Previous studies demonstrated the etiological role of human papilloma virus (HPV) in cervical carcinogenesis. Assessing the distribution of HPV may elucidate these observations.
Materials and Methods:
In total, we examined 3839 specimens, of which 187 abnormally classified cervical smears were immunostained using the p16INK4A assay. DNA was extracted from 182 specimens, and polymerase chain reaction (PCR) was performed. Participants’ socio-demographics, sexual and reproductive history, HIV status, contraceptive use, and Pap smear history were recorded.
Results:
Subject ages, number of sexual partners, and age at first sexual encounter ranged from 15 to 49 years, from 1 to 37 partners, and from 13 to 34 years, respectively. P16 immunoreactivity was detected in 60.4% of cases. The distribution of epithelial lesions and P16 overexpression (bracketed) was: 28 (5) atypical squamous cells of undetermined significance (ASC-US), 96 (50) lower grade squamous intraepithelial lesion (LSIL), 9 (7) atypical squamous cells-cannot exclude HSIL (ASC-H), and 54 (51) higher grade squamous intraepithelial lesion (HSIL). Ninety-four percent of HSIL expressed P16. Fifty-two percent of LSIL expressed P16. P16 expression declined from 61% (25–34 year age group) to 5% (45–49 year age group) for different age groups. HPV-DNA by PCR was detected in 94.5% of P16-positive samples. Type-specific PCR (HPV 16 and 18) was found in 12.2% and 14.5% of abnormal lesions, respectively. Younger age at first sexual encounter and HIV infection predominated in HPV type(s) 16 and/or 18 positive subjects.
Conclusion:
This study reinforced the value of the p16INK4A surrogate marker in identifying women with progressive cervical disease.
doi:10.4103/1742-6413.100123
PMCID: PMC3440928  PMID: 22993533
Cervical cancer; human papilloma virus; Namibia; p16INK44A stain
19.  Cost-effectiveness analysis of human papillomavirus DNA testing and Pap smear for cervical cancer screening in a publicly financed health-care system 
British Journal of Cancer  2010;103(12):1773-1782.
Objective:
To evaluate the long-term cost-effectiveness of different strategies for human papillomavirus (HPV) DNA testing combined with Pap smear for cervical cancer screening in Taiwan.
Methods:
This study adopts a perspective of Department of Health in cost-effectiveness analysis to compare a no-screening strategy with nine different screening strategies. These strategies comprise three screening tools (Pap smear alone, HPV DNA testing followed by Pap smear triage, and HPV DNA testing combined with Pap smear), and three screening intervals (annually, every 3 years, and every 5 years). Outcomes are life expectancy, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analyses (PSAs) were conducted to assess parameter uncertainty.
Results:
When three times gross domestic product per capita is used as the decision threshold, all nine screening strategies were cost-effective compared with the no-screening strategy. Compared with the current screening strategy (an annual Pap smear), HPV DNA testing followed by Pap smear triage every 5 years and every 3 years were cost-effective. Results of PSA also indicated that a HPV DNA testing followed by Pap smear triage every 5 or every 3 years achieved the highest expected net benefits.
Conclusions:
Possible economic advantages are associated with extending the cervical cancer screening interval from one Pap smear annually to HPV DNA testing followed by Pap smear triage every 5 years with an ICER $1 247 000 per QALY gained, especially in a country with a publicly financed health-care system.
doi:10.1038/sj.bjc.6605974
PMCID: PMC3008604  PMID: 21102588
HPV DNA testing; Pap smear; cost-effectiveness analysis; cervical cancer; screening
20.  Knowledge and Acceptability of Pap Smears, Self-Sampling and HPV Vaccination among Adult Women in Kenya 
PLoS ONE  2012;7(7):e40766.
Objectives
Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.
Methods
Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit.
Results
Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost.
Conclusions
These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.
doi:10.1371/journal.pone.0040766
PMCID: PMC3393696  PMID: 22808257
21.  Awareness of cervical cancer screening among nursing staff in a tertiary institution of rural India 
Journal of Gynecologic Oncology  2012;23(3):141-146.
Objective
To determine the baseline information about the knowledge of cervical cancer and explore attitude and practice of Pap smear screening among staff nurses.
Methods
A pretested structured self administered questionnaire based survey was done on 205 staff nurses working in Rural Institute of Medical Sciences & Research, Saifai, Etawah, containing mostly recognition and some recall type questions about demographics, knowledge about cervical cancer, its risk factors, screening techniques, attitudes towards cervical cancer screening and its practices.
Results
In this study, 74% knew that Pap smear is used for detection of cervical cancer, but only 59% knew that it can detect both cancerous as well as precancerous lesions of the cervix. Only 18% of the respondents knew about human papillomavirus vaccine. A 47% of respondents had never taken a Pap smear; 63% never referred patients for the screening. Most nurses (79%) thought that a speculum examination and Pap smear are procedures to be performed by the doctors. Among all the respondents, only 11% had ever undergone a Pap smear on themselves.
Conclusion
Despite knowledge of the gravity of cervical cancer and prevention by screening, attitudes and practices towards screening were negative.
doi:10.3802/jgo.2012.23.3.141
PMCID: PMC3395008  PMID: 22808355
Cervical cancer; Pap smear; Screening attitude
22.  New insights into cervical cancer screening 
Journal of Gynecologic Oncology  2012;23(4):282-287.
Worldwide, cervical cancer is a leading cause of cancer related morbidity and mortality. For over 50 years, cervical cytology has been the gold standard for cervical cancer screening. Because of its profound effect on cervical cancer mortality in nations that have adopted screening programs, the Pap smear is widely accepted as the model screening test. Since its introduction, many studies have analyzed the Pap smear and found that it is not without its shortcomings including low sensitivity for detection of cervical intraepithelial neoplasia 2/3. Additionally, the discovery of infection with the human papillomavirus (HPV) as a necessary step in the development of cervical cancer has led to the development of HPV testing as an adjunct to cytology screening. More recently, researchers have compared HPV testing and cytology in the primary screening of cervical cancer. In this review, we will discuss cytologic testing limitations, the role of HPV DNA testing as an alternative screening tool, the impact of the HPV vaccine on screening, and future directions in cervical cancer screening.
doi:10.3802/jgo.2012.23.4.282
PMCID: PMC3469864  PMID: 23094132
Co-testing; Cytology; HPV vaccine; Pap smear limitations; Screening
23.  Cytological pattern of cervical Papanicolaou smear in eastern region of Saudi Arabia 
Background:
Cancer of the cervix has been considered as one of the preventable cancers. This study is the first published research addressing the screening of cancer of the cervix in the eastern region of Saudi Arabia.
Aim:
This study aims to detect the prevalence of abnormal epithelial changes and its types in the eastern region of Saudi Arabia.
Settings and Study Design:
A retrospective study was designed to evaluate all previously conducted cervical smears examined at a secondary care maternity hospital in Saudi Arabia, during the period from 2003 to 2010. During this period, a total of 1171 smears were reported.
Materials and Methods:
We analyzed the records of all patients who had undergone Papanicolaou (Pap) smear during this period. After data collection, all cases were recorded as per Bethesda nomenclature.
Results:
A total of 624 (53.3%) abnormal Pap smears were found, with only 58 cases reported to have epithelial pathological diagnosis (SIL). They represented 4.95% of total taken smears. A majority of the SIL diagnoses in our population were ASCUS, representing 60% of SIL cases. The prevalence of squamous cervical carcinoma was 0.34%.
Conclusion:
The study has shown a relatively high prevalence of epithelial abnormalities in cervical smears in the studied population. The squamous cell carcinoma represented a higher than the overall prevalence compared to World Health Organization (WHO) factsheets about Saudi Arabia. The mean age of epithelial abnormalities and squamous cell carcinoma was in the reproductive years.
doi:10.4103/0970-9371.86343
PMCID: PMC3214461  PMID: 22090690
Cervical cytology; pap smear; Saudi Arabia
24.  Cytomorphology of cervicovaginal melanoma: ThinPrep versus conventional Papanicolaou tests 
CytoJournal  2010;7:25.
Background:
Primary cervicovaginal melanoma is a rare malignancy associated with a high risk of recurrence. Prior studies discussing the cytomorphology of cervicovaginal melanoma have been based primarily on review of conventional Papanicolaou (Pap) smears. The aim of this study was to evaluate cervicovaginal melanomas identified in liquid-based Pap tests, in comparison with features seen on conventional Pap smear preparation.
Materials and Methods:
Cases of cervicovaginal melanoma identified on Pap tests with concurrent or subsequent histopathologic confirmation were collected from the Baystate Medical Center cytopathology files and personal archives of the authors over a total period of 34 years. All cytopathology (n = 6) and the available histology slides (n = 5) were reviewed. Cases were analyzed regarding clinical, histopathologic and cytomorphological findings.
Results:
A total of six cases with invasive cervicovaginal melanoma diagnosed on Pap tests were identified. Most patients were postmenopausal with contact bleeding, correlating with surface ulceration (identified in biopsy/excision material in 5/5 cases). Most cases had deeply invasive tumors (5/5: modified Breslow's thickness > 5 mm and Chung's level of invasion IV/V). Pap tests included four ThinPrep and two conventional smears. Overall, ThinPrep Pap tests exhibited a higher ratio of tumor cells to background squamous cells. While all Pap tests were bloodstained, tumor diathesis was prominent only within conventional smears. Melanoma cells were present both as clusters and scattered single cells in each Pap test type. Both the preparations contained epithelioid tumor cells, whereas spindled tumor cells were seen in only two ThinPrep cases. Prominent nucleoli and binucleation of tumor cells were seen in both the preparations. Melanin pigment was identified in only ThinPrep (3/4) cases and nuclear pseudo-inclusions in one conventional Pap smear. Cell blocks were made in three ThinPrep cases and immunocytochemistry (S-100, HMB45, Melan-A) performed on additional vial material (one ThinPrep slide and one cell block) was immunoreactive in melanoma cells.
Conclusion:
Primary cervicovaginal melanoma, a rare malignancy seen predominantly in postmenopausal women, may be successfully diagnosed in either ThinPrep Pap tests or conventional Pap smears. While ThinPrep Pap tests did not demonstrate morphological advantage over conventional smears, liquid-based cytology specimens did provide additional material for cellblock preparation and immunocytochemical evaluation in a subset of cases.
doi:10.4103/1742-6413.75666
PMCID: PMC3030001  PMID: 21298024
Cervix; conventional smear; cytology; melanoma; Pap test; ThinPrep; vagina
25.  The accuracy of Pap smear utilization self-report: a methodological consideration in cervical screening research. 
Health Services Research  1991;26(1):97-107.
One method used to determine utilization rates of cervical screening is women's self-report. Few studies have assessed the accuracy of this measure--none has been conducted in Australia--although there are a number of reasons for suspecting its validity. This study examined and quantified the accuracy of self-report of Pap smear use among a randomly selected sample of women from an Australian community. Accuracy of Pap smear utilization self-report within a three-year period was assessed by comparison with pathology records. Results indicated that almost half of the women who have not had Pap smears within three years will be missed by a self-report measure of utilization. Some implications for the measurement and use of self-report data are discussed.
PMCID: PMC1069812  PMID: 2016170

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