Normal Cervical Smears Research Articles

Human papillomavirus-DNA test in patients with abnormal cervical smears: A tool to improve the detection of invasive cervical cancer in early stages

ABSTRACT Introduction: Cervical cancer is the second most frequent cancer among women in developing countries. Human papillomavirus (HPV) can be detected in 99.7% of cervical cancers. Its detection can be used as a tool to detect women, at risk for consequent development of cervical cancer. The objective of the study was to determine the prevalence of high-risk HPV in women with or without cervicitis and to evaluate the associated risk factors. Materials and Methods: A total of 66 patients who met with the inclusion criteria were included as case group. Thirty cytologically normal cervical smears were also included as a control and were collected from asymptomatic patients. Two cervical specimens were collected for Pap smear and HPV 16/18 reverse transcription polymerase chain reaction (PCR). Results: In the case group, 45.5% of patients had abnormal cervical cytological findings and majority of them had one or more menstrual abnormalities and vaginal infection, as compared to control group (P < 0.5). 13.6% of patients were HPV-PCR positive in the case group compared with none in the control group. In the HPV-positive group, the mean age was of 50.26 ± 13.293 years, while in the HPV-negative group, it was 35.29 ± 8.768 years (P < 0.0001). The rate of positivity of HPV-DNA test increased as the severity of dysplastic changes increased in cervical cytology. Conclusion: HPV-DNA testing should be used as an adjunct to Pap smears for the detection of cervical precancerous lesions and cervical cancer at its early stages.

Prevalence of anal dysplasia and HPV genotypes in gynecology patients: The ANGY cross-sectional prospective clinical study protocol.

BackgroundHuman Papillomaviruses (HPV) are highly prevalent in the sexually active populations, with a significant burden in terms of health and psychological cost in all class ages. High-risk (HR) HPV genotypes are associated with anogenital dysplasia and cancers, and anal HPV-induced cancer is increasingly observed in women. The interactions of HPV genotype’s between the anus and the cervix, and the subsequent occurrence of dysplasia remains unclear. This clinical study set out to test the hypothesis that risk factors for anal HR-HPV and dysplasia may differ in women with or without cervical dysplasia or in HIV-positive women.MethodsCervical and anal HPV genotypes and cytology testing will be performed prospectively in a cohort of women recruited in a tertiary university hospital in Switzerland. Women will be allocated to three groups: 1) normal previous cervical smear; 2) high-grade cervical dysplasia (H-SIL) at previous cervical smear; 3) HIV+, independently of previous cervical smear result. General inclusion criteria comprised the followings: Female—Age > = 18 years; Satisfactory understanding of French; No objection to HIV testing. Specific inclusion criteria are: Group 1, no past or current gynecological dysplasia and HIV negative; Group 2, Gynecological dysplasia (H-SIL) or carcinoma in situ demonstrated by histology (vulvar, vaginal or cervical) and HIV negative; Group 3: HIV-positive (regardless of viremia or CD4 count) with or without gynecological dysplasia. General exclusion criteria are: Pregnancy; History of anal dysplasia/cancer; Status after pelvic radiotherapy; Absence of anus and anal canal. Estimated prevalences of anal dysplasia are: in group 1, 1% (0–2%); in group 2, 15% (5–27%), and in group 3, 30% (19–45%). With a 10% margin error, a sample size of 120 women per group is required to reach 90% power for detecting statistical significance (unilateral α error of 5%).DiscussionThe primary endpoint is the prevalence of anal and cervical dysplasia, and description of the respective HPV genotypes in each group. The results of this study could improve the standard of screening of cervical and anal dysplasia in women through evidence of concomitant presence of HPV’s and/or dysplasia in anus or cervix to support vaccination for instance. Beginning of recruitment started in September 2016. Results should be presented in end of 2022. Preliminary analysis for first 100 patients reveals that the mean age of the population is 39.6 (± 10.9) years with mean age of first sexual intercourse of 18.5 (± 3.9) years. In this cohort, 12% are vaccinated and 38% having had anal intercourse. Overall, 43% of the studied population had cervical HR-HPV in the studied population, and 53% had normal cytology. Anal LR HPV and HR HP were found in 27.6% and 38.4% of all patients respectively. Eighty percent had normal anal cytology. Groups 1,2 and 3 had a significant difference in terms of age, gestity, parity, age of first sexual intercourse, systematic use of condom, number of cervical LR HPV and HR HPV and abnormal cervical cytologies.Trial registrationThe study was approved by the institutional review board—CER-VD#2015–00200—on the 29th of June 2016 and is registered on the Swiss National Clinical Trials Portal (SNCTP), SNCTP000002567, Registered 29 June 2016, https://www.kofam.ch/en/snctp-portal/study/40742/

Digital cervical cancer screening: a reliable One-Stop method ?

BackgroundWorldwide, cervical cancer (CC) is considered the fourth most common cancer in women. Globocandata stated 311,365 CC related mortalities in the world in 2018, 90% of them occurred in low-income countries. In Jordan, CC ranks as the 12th most common cancer among women. The primary aim of this report is to be able to decide if digital screening (DS) is reliable and worth using in our one stop gynecology clinics. Materials and MethodsThis study was done for all women who attended one stop out-patient gynecology services for routine CC screening between 1/1/2019 and 31/12/2019. Inclusion criteria requested women to be 18 years of age or more, healthy, and had previously normal cervical smear (conventional Pap smear (CPS) or Liquid based cytology (LBC)) i.e., all previous screening tests results were normal. ResultsA total number of 94 patients agreed to have the DS method done, mean age was 43 years. 25.5% were found to have abnormal screening results on DS. When compared to the national data of 12.5% abnormal smears in Liquid‐based cytology (LBC), there was a statistically significant difference in the numbers of abnormal screening results between both methods (p value of 0.000). LBC is used in most centers for CCS in Jordan ConclusionThe digital cervical screening method saves time and offers a one stop clinic management, therefore minimizing lost to follow up rate, and where colposcopy is indicated. Additionally, DS should be considered in low resource countries.

Human Papillomavirüs (HPV), Servikal Smear ve Kolposkopik Biyopsi Sonuçlarının Karşılaştırılması: Serviks Kanseri Taramasında Bir Üniversite Hastanesinin 4 Yıllık Deneyimi

Aim: Cervical cancer screening guidelines gradually recommend human papillomavirus (HPV) DNA testing since sensitivity of cytology is relatively low. This study aimed to evaluate correlation between HPV, cervical smear cytology and colposcopy directed biopsy results.
 Material and Methods: Patients who underwent colposcopy directed biopsy in Ordu University Training and Teaching Hospital between January 2018 and December 2021 were retrospectively reviewed. Patients with any high-risk HPV positivity who had cervical smear cytology and colposcopy directed biopsy results were included to this study. Results of HPV subtypes, cervical smear and histologic biopsy were recorded.
 Results: A total of 734 patients were included to this study. The mean age of the patients was 41.9 ± 7.36 years. Hundred and sixty-five (22.5%) patients had HPV 16 alone, 35 (4.8%) had HPV 18 alone, 354 (48.2%) had other high-risk HPV subtypes alone and 180 (24.5%) had more than one high-risk HPV subtypes. Two hundred and ninety-eight (40.6%) had HPV 16 or HPV 18 either alone or in combination with other subtypes. Majority of the patients (55.3%) had normal cervical smear results followed by ASC-US (27%). Colposcopy directed biopsy results were as follows: 452 (61.6%) normal, 199 (27.1%) CIN 1, 36 (4.9%) CIN 2, 42 (5.7%) CIN 3 and 5 (0.7%) squamous cell cancer. 66.1% of the patients with HPV 16 and/or HPV 18 had normal cervical cytology results, but they had significantly more ≥CIN 2 lesions compared to other high-risk HPV subtypes (19.8% vs 5.5%, p

Reporting reactive cellular changes on smears among women who undergo cervical cancer screening: results of a cohort study after seven years of follow-up

ObjectiveTo identify whether women presenting with reactive cellular changes (RCC) on their cervical smear face an increased risk for developing high grade cervical intraepithelial neoplasia (CIN2-3) or cancer as compared with women with an entirely normal smear. Study designFrench data from the association in charge of organized cervical cancer screening in Bas-Rhin administrative region were used to establish a cohort of 96,215 women presenting with a smear classified as entirely normal or with RCC during the year 2001. The Kaplan-Meyer method was used to calculate the probabilities of CIN2-3 and cancer at seven years of follow-up. Univariate and multivariate survival analyses were performed using Cox proportional hazard models. ResultsAmong the 95,559 women included in the final analysis, 32.2% presented a smear with RCC. After seven years of follow-up, 441 women developed a CIN2-3 and 35 a cancer. Probability of CIN2-3 was increased in the RCC group as compared with the group of women with a normal smear (0.7% versus 0.5%, p=0.002). Multivariate analyses showed that, compared with a normal cervical smear, RCC were associated with a significant 37% increased risk of CIN2-3 (HR=1.37 CI95 [1.13–1.66]). However, the risk of cancer was not significantly increased (HR=1.11 CI95 [0.55–2.23]). ConclusionThis study showed that, at seven years, women with RCC on their cervical smear face an increased risk of CIN2-3 but no significant increased risk of cancer. The distinction between entirely normal and RCC cervical smears should therefore not lead to specific clinical management.

Profile of POT1 as telomerase shelterin component discriminatesbetween cervical cancer and normal cervical cells.

Telomerase activity is influenced by hTERT transcriptional regulation, shelterin, and posttranscriptional alternative splicing. Telomerase shelterin such as POT1 is highly correlated with various cancers. However, the profile of POT1 in cervical cancer has not been clearly identified. Therefore, it is important to identify its profile in cervical cancer biopsy tissue and normal cervical smears. Biopsy tissue of cervical cancer patients and normal cervical smears were characterized using SDS-PAGE and western blot. Sixteen biopsy tissues of cervical cancer patients and 15 normal cervical smears were measured for POT1 level using ELISA. The inline band at 70 kDa indicated that all samples had protein that was identified as POT1. Western blot showed that telomerase antibody only recognized POT1 in biopsy tissue of cervical cancer patients. There was a significant difference (P = 0.01) in POT1 level between biopsy tissue of cervical cancer patients and normal cervical smears. POT1 was identified at 70 kDa in biopsy tissue of cervical cancer patients and its level was higher than that in normal cervical smears. The high level of POT1 in the biopsy tissue of cervical cancer patients showed the influence of this shelterin component in cervical carcinogenesis and also cell immortalization.

Prevalence of abnormal oral cytology and impact of sexual behavior in women with abnormal cervical cytology

Purpose of investigation: To assess the frequency of oral cytological abnormalities in women who have cervical intraepithelial lesions, and transmission of infection depending on their sexual behavior. The authors also aimed to investigate the oral cytological changes in male partners. Material and Methods: Thirty patients with abnormal cervical cytological results via punch biopsy formed the case group, and 68 patients constituted the control group with normal cervical smear results. The Bethesda system was used for classification of the cytological alterations. Results: Oral dysplasia was significantly higher in the squamous intraepithelial lesion (SIL) group. Oral sex percentage was 43.3% in SIL group, whereas it was 19.1% in the control group. History of genital warts in women with SIL was also significantly higher in the case group. Three patients were diagnosed with abnormal oral cytology in the SIL group (10%), however abnormal oral cytology was not detected in the control group. No oral dysplastic changes was identified in the male partners of women with oral lesions. Conclusion: The authors detected oral dysplastic changes in the SIL group, especially in the (low grade squamous intraepithelial lesion (LGSIL) patients. Interestingly they could not find any oral dysplastic changes in the male partners of the study population.

Human papillomavirus genotypes among women with or without HIV infection: an epidemiological study of Moroccan women from the Souss area.

BackgroundData on Human PapillomaVirus (HPV) infection are scarce in Morocco. The objective of the study was to determine the prevalence of HPV and cervical cytology abnormalities in women from the Souss area, Morocco.MethodsTwo hundred and thirty two women who attended the Hassan II hospital (Agadir, Morocco) were recruited in this study. Socio-economic data, sexual activity, reproductive life, history of Pap smear, smoking and HIV status were recorded. Cervical samples were taken using an Ayre spatula. Cytology was reported using the Bethesda system. HPVs were first detected by MY09/11 consensus PCR and then genotyped with INNO-LiPA® assay. Data were analyzed using the logistic regression model.ResultsThe median age of women was 42 years (18–76 years). HIV prevalence was 36.2 %. Any HPV type prevalence was 23.7 % in the study population, lower in HIV-negative women (13.3 %) than in HIV-positive women (39.3 %). HPV16 was the most prevalent type (6.5 %), followed by HPV53 and HPV74 (3.4 % each). Most women had normal cervical smears (82 %), the remaining were diagnosed with LGSIL (13 %) and HGSIL (5 %). HPV was detected in 17.4 % of normal smears, 43.4 % of LGSIL and 75 % of HGSIL. HIV status was the most powerful predictor of high risk (hr) and probable hr (phr) HPV infection (odds ratio 4.16, 95 % confidence interval 1.87–9.24, p = 0.0005) followed by abnormal cytology (OR 3.98, 95 % CI 1.39–11.40, p = 0.01), independently of socio-demographic and behavioral risk factors.ConclusionsIn a Moroccan hospital based-population of the Souss area, HPV infections are frequently detected. In addition, high prevalence of hr and phrHPVs and precancerous lesions among HIV-positive women is likely associated with an increased risk of cervical cancer. This highlights the need for HPV and cervical cancer prevention campaigns in Morocco.

Exploration of treatment strategies for normal cytology smears with reactive cellular changes

ObjectiveTo evaluate the use of high-risk humanpapillomavirus (HR-HPV) DNA testing in women who have normal cytology result with reactive cellular changes to identify high risk patients of developing precancerous cervical lesions and cervical cancer. Study designOutpatient patients with normal liquid-based cytology (LCT) results showing reactive cellular changes (case group, n=1085) and normal LCT without reactive cellular changes (control group, n=1085) were recruited from cervical clinics at the International Peace Maternity & Child Health Hospital from January 2012 to December 2013. The HPV status and cervical biopsy pathology results were analyzed. ResultsThe HR-HPV positive rate of the case group (598/1085) was higher than that of the control group (163/1085) (P<0.001). HR-HPV prevalence among CIN1, CIN2, CIN3 and cervical cancer was 73%, 87%, 100%, and 100% respectively (P<0.05). In patients with positive HR-HPV results, more CIN2+ were found significantly in case group (37/598) than those in control group (3/163), P=0.027. The sensitivity of diagnosis of CIN2+ lesions by HR-HPV testing was 92.5%, the specificity was 36%, the positive predicted value was 8.6%, and the negative predictive value was 98.6%. The incidence of CIN2+ lesions was not different among different age groups (P>0.05). ConclusionReactive cellular changes in normal cervical smears should be further investigated. HR-HPV testing could be used as an effective triage in cases of reactive cellular changes. Colposcopy is recommended for those cases showing reactive cellular changes combined with HR-HPV positivity to reduce the risk of failure to diagnose cervical cancer and precancerous lesions.

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

BackgroundAustralia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12–26 years. ObjectiveTo identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase. Methods1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008–2009 (age 20–29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors. ResultsOverall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p<0.01), being single (p=0.02), being nulliparous (p<0.01), living in a higher socioeconomic status area (p-trend=0.03), living in more remote areas (p=0.03), drinking alcohol (p<0.01) and using hormonal contraceptives (p<0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend=0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p=0.03). Similar factors were associated with receiving ≥2 doses. ConclusionsIn this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups.

Vaginal hysterectomy for uterovaginal prolapse: what is the incidence of concurrent gynecological malignancy?

Vaginal hysterectomy (VH) is a commonly performed procedure for the operative treatment of uterovaginal prolapse (UVP). The reported incidence of unexpected gynecological cancer in cases of VH for UVP ranges between 0.3 and 0.8 %. Aim of the study is to assess the incidence of malignant and premalignant gynecological histopathological findings among women who underwent a VH for UVP and had a normal preoperative workup. The histopathology reports of women who underwent VH for the treatment of UVP were retrospectively assessed. All women had a history of normal cervical smear tests and a normal preoperative transvaginal scan. Patients with a history of a premalignant or malignant gynecological pathological condition and women with abnormal uterine bleeding were excluded. Overall, 14 out of 333 women who underwent VH (4.2 %) were found to have abnormal histopathological findings of the uterus. Among them, there were 9 cases of endometrial hyperplasia of any type (2.7 %), 1 case of cervical cancer (0.3 %), 1 case of cervical intraepithelial neoplasia (CIN) III (0.3 %), and 3 cases of CINI (0.9 %). No cases of endometrial cancer were detected. Among women who underwent salpingo-oophorectomy (n = 86) three simple serous cysts (3.5 %) were found, with no cases of ovarian cancer. The incidence of unexpected premalignant or malignant gynecological pathological conditions among asymptomatic women who underwent VH, with a history of normal cervical smear tests and normal preoperative TVS, was low but not negligible. This information should be included in the preoperative counseling of women planning to undergo surgery for UVP.

Human papillomavirus genotype distribution and E6/E7 oncogene expression in Turkish women with cervical cytological findings.

Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor related with cervical cancer. The objective of the present study was to investigate the prevalence of HPV infection, the distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish women with different cervical cytological findings in Mersin province, Southern Turkey. A total of 476 cytological samples belonging to women with normal and abnormal cervical Pap smears were enrolled in the study. For the detection and genotyping assay, a PCR/direct cycle sequencing approach was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQ(®)HPV v1.1). Of the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology (72/380, 18.9%). The most prevalent genotypes were, in descending order of frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%), and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than DNA positivity (38/476, 7.9%). Our data present a wide distribution of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and 83 were the predominant types and most of them were potential carcinogenic types. Because of the differences between HPV E6/E7 mRNA and DNA positivity, further studies are required to test the role of mRNA testing in the triage of women with abnormal cervical cytology or follow up of HPV DNA positive and cytology negative. These epidemiological data will be important to determine the future impact of vaccination on HPV infected women in our region.

Association between human papillomavirus (HPV) DNA and micronuclei in normal cervical cytology.

The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population's exposure to HPV.

MMP‐9 expression increases according to the grade of squamous intraepithelial lesion in cervical smears

Studies about cervical carcinogenesis have demonstrated the increased expression of matrix-metalloproteinase (MMP) according to the grade of cervical intraepithelial lesions. Considering the importance of innovative techniques to introduce noninvasive and rapid diagnoses for patients, this study aimed to perform MMP-9 immunocytochemistry in cervical smears according to the cytopathological diagnoses, in order to monitor MMP activity in cervical smears. This cross-sectional study investigated the expression of MMP-9 in normal cervical smears, inflammatory cervical smears, squamous intraepithelial lesions, and cervical carcinoma. Cervical smears from 630 women were collected for cytopathological diagnoses and immunocytochemistry. Women with squamous intraepithelial lesions showed an increase in MMP-9 expression, with moderate to intense staining occurring with increasing cervical lesion grade. The prevalence of moderate to intense MMP-9 staining was 9% in normal cervical smears, 12% in cervical inflammation, 24% in low-grade squamous intraepithelial lesion (LSIL), 92% in high-grade squamous intraepithelial lesions (HSIL) and 100% in cervical carcinoma cases. In the specific case of LSIL, we found that association with MMP-9 is more evident when there is the simultaneous presence of an infectious agent. Thus, the expression of MMP-9 in cervical smears increases according to the grade of cervical lesion and LSIL in the presence of infectious agents showed higher MMP-9 expression than women with LSIL without infectious agents.

The Pattern of Cervical Cytology in Women Attending Various Clinics at a Tertiary Hospital in Anambra Southeast, Nigeria

Background: Cervical cancer is one of the most common female reproductive tract malignancies with high morbidity and mortality most especially in the developing countries. Our purpose of this study is to determine the pattern of cervical smear and also to determine the effect of socio-demographic factors on the pattern of cervical cytology among women attending gynaecological clinic in Nnewi, Southeast Nigeria. Materials and Methods: This cross-sectional prospective study was conducted at Nnamdi Azikwe University Teaching Hospital, (NAUTH), Nnewi, Anambra state, in South East Nigeria from December 2007–July 2008. Result: Ninety six (68.6%) of the women had normal cervical smear while forty one (29.3%) had abnormal cervical smear. The proportion of unsatisfactory smear was 2.1%. The number and rates of abnormal cervical smear was further sub-classified as LSIL (25 cases, 17.9%), HSIL (12 cases, 8.6%), ASC-US (3 cases, 2.1%) and glandular Original Research Article British Journal of Medicine & Medical Research, 4(33): 5218-5228, 2014 5219 intraepithelial lesion (1 case, 0.7%). No case of squamous cell carcinoma was detected. Conclusion: The study shows that various patterns of abnormal cytology were found among our women and the prevalence of this abnormal smear is high. these findings underscore the need for massive and sustained reproductive health education and establishment of cervical cancer screening centres.

A frailty model for interaction between multiple events

Most models for categorical data rely on linear models in which higher order interactions are limited, usually to second order terms. Here we explore a dataset where second order interactions lead unavoidably to high order interactions. However in certain cases these interactions have a simple form which can be explained by population heterogeneity or ‘frailty’ and the Rasch model which uses a logistic structure is one such model. However its parameters are difficult to interpret. When event probabilities are low, we develop a simple model based on a multiplicative structure and a one-parameter gamma frailty model is developed to accommodate this sort of data. Moment estimators estimates are also provided for more general cases and goodness of fit statistics are given. An example involving 35 different human papillomavirus types in 33614 women with normal cervical cytology smears (stratified by age) is explored.

Prevalence of high risk human papillomavirus types 16/18 in cytologically abnormal cervical smears in Alexandria, Egypt. A cytological and molecular study

In Egypt, cervical cancer ranks as the second most frequent cancer after breast cancer, among women between 15 and 44 years of age. High-risk human papillomavirus (HPV) 16 and 18 detection holds the potential to be used as a tool to detect women, at risk for consequent development of cervical cancer because of their predominance and potentially greater oncogenic nature than other high risk HPV subtypes. To determine the prevalence of high-risk HPV 16/18 DNA in women with abnormal cervical cytology. 45 cases were collected from Egyptian women seeking routine gynecologic care. Ten cytologically normal cervical smear cell samples were included in the study as a control to be tested for the presence of HPV 16/18 DNA and were collected from asymptomatic patients having cystorectocele or coming for loop insertion or removal. The 45 specimens were subjected to real-time polymerase chain reaction, using multiplex HPV 16 and 18 PCR kit. 45 cervical smears were collected in the present study. Cytopathological examination revealed that 5 (11.1%) were ASCUS, 8 (17.8) were LSIL, 5 (11.1%) were HSIL, 1 (2.2%) was squamous cell carcinoma (SCC), 1 (2.2%) was adenocarcinoma and 25 (55.6%) were benign (inflammatory). 20 patients with abnormal cervical cytology and 10 controls were included in the present study. In patients with abnormal cervical cytology, 5 (25%) were ASCUS, 8 (40%) were LSIL, 5 (25%) were HSIL, and 1 (5%) was SCC and 1 (5%) was adenocarcinoma. Statistical analysis revealed a significant difference between patient and control groups as regards regularity of menstruation where irregular menstruation and higher prevalence of menopausal women, abnormal vaginal bleeding, menorrhagia, vaginal infection, and abnormal cervical appearance were encountered in patients. A statistically significant higher prevalence of married women was found in the control group. There was no significant difference in the distribution of patients and control as regards HPV 16 or HPV 18 in which 20% of patients were HPV 16 positive and 10% of patients were HPV 18 positive compared with none in the control group. 6 were positive either for HPV 16 or 18, while 39 were negative. The HPV 16/18 positive patients had significantly higher age and marital duration when compared with HPV 16/18 negative group. Significantly, most of the HPV 16/18 positive patients were menopause. A significantly higher prevalence of women with cervicitis, contraceptive users and married women was in the HPV 16/18 negative group. The study generates epidemiological data of prevalence of HPV 16/18 in cytologically abnormal cervical smears in women seeking routine gynecologic care at the outpatient clinics of the Obstetrics and Gynecology Department at El Shatby University. High-risk HPV DNA testing by PCR of cervical samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with abnormal cervical smears, especially among women aged 46 years and older, in menopausal women and in women complaining of PMB. Therefore, HPV DNA testing should be made use of as an adjunct to cervical smears.

Incidence of cytological abnormalities within 24 months of a normal cervical smear in Soweto, South Africa

A screening programme for cervical cancer has been implemented in South Africa (SA) with intervals of 10 years after a normal cytological result. There are no studies that evaluate repeat screening at a shorter interval in SA. (i) To find the incidence of cytological abnormalities on a repeat test after a report of normal cytology or an inadequate Pap smear; and (ii) to explore the factors associated with an abnormal cytology on repeat testing. This was a secondary data analysis of a randomised controlled trial of diaphragm, lubricant gel and condoms v. condoms in the prevention of HIV infection. HIV-negative women were recruited between November 2003 and December 2005, with a normal Pap smear at entry. Observation time was from the first Pap smear to the date of the repeat Pap smear. Explanatory variables used were baseline, excepting any new HIV infection. The incidence of cytological abnormalities was 6.48% yearly in women with a previously normal Pap smear and 11.71% yearly in women with an inadequate smear result (p=0.03). The incidence of high-grade squamous intra-epithelial lesions (HSILs) was <0.5%. Factors associated with abnormal cytology were a history of ectopic pregnancy (odds ratio (OR) 9.25; confidence interval (CI) 1.78 - 48.02; p=0.01), number of male partners (OR 1.12; CI 1.03 - 1.22; p=0.01), history of vaginal discharge (OR 13.95; CI 1.18 - 164.47; p=0.04), and incident HIV infection (OR 6.56; CI 1.14 - 38.16; p=0.04). The incidence of HSILs is low in the first 2 years after a normal or inadequate Pap smear, even in a setting with a high prevalence of cytological abnormalities.

A Clinical Study of Cervical Dysplasia in Long-Term Survivors of Allogeneic Stem Cell Transplantation

This retrospective study examined the prevalence of and risk factors for cervical dysplasia and genital human papillomavirus (HPV) infection in 89 female recipients of allogeneic stem cell transplantation (allo-SCT) between 1985 and 2005 who survived for more than 5 years after transplantation. All patients underwent regular gynecologic examination and cervical cytological testing. The incidence rates of cervical cytological abnormalities and HPV infection were calculated. Various clinical parameters were evaluated for association with cytological high-grade squamous intraepithelial lesion (HSIL) posttransplantation to identify risk factors for cervical dysplasia. Multivariate analysis with logistic regression was used to identify independent risk factors for cervical dysplasia after adjusting for confounding factors. Sixty-one of the 89 patients (68.5%) had cervical cytological abnormalities of varying grades, including atypical squamous cells of undetermined significance (ASC-US; 31.5%; 28 of 89), low-grade squamous intraepithelial lesion (LSIL; 10.1%; 9 of 89), and HSIL (27%; 24 of 89). HPV status was available for 43 patients, 12 of whom (27.9%) were HPV-positive. Among the 69 patients with normal cytological cervical smear findings pretransplantation, the incidence of cytological HSIL was 23.2% (16 of 69) posttransplantation. After adjusting for confounding factors, only unrelated HLA-matched donor and the presence of vulvovaginal chronic graft-versus-host disease (cGVHD) were independent risk factors for cervical cytology HSIL after transplantation, with the highest risk among patients with vulvovaginal cGVHD (adjusted odds ratio, 31.97). We conclude that long-term survivors of allogeneic stem cell transplantation are at high risk for cervical cytological abnormalities. Vulvovaginal cGVHD and unrelated HLA-matched donor were the only independent risk factors for cervical cytological HSIL in patients with normal cervical cytology before transplantation. Regular surveillance by gynecologic examination, including cervical cytological testing, in these patients allows for early diagnosis and effective management of cervical abnormality and decreases the burden of this potentially fatal, but treatable, condition.

Patients with cervical cancer: why did screening not prevent these cases?

The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis. Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed. Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear. Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.