Self-Collected Samples for Testing of Oncogenic Human Papillomavirus: A Systematic Review

BackgroundTo investigate the role of self-sampling for human papillomavirus (HPV) testing as an alternative to cervical cancer screening by clinicians (i.e., Papanicolaou [Pap] test).MethodsA systematic search of MEDLINE, EMBASE, Cochrane Library, and other sources for evidence related to the efficacy and feasibility of HPV DNA self-collection.ResultsA total of 25 studies were identified. In 22 comparisons across 19 studies, the concordance between samples collected by patients and those obtained by clinicians was reasonably high in the majority of cases. Women in many countries across wide age ranges were successful in collecting samples for HPV DNA testing. In four studies, the quality of the cytology from patient samples was as good as clinician samples, with more than 95% of samples yielding HPV DNA results. The studies that examined acceptability found that women were generally very positive about collecting their own samples, although some concerns were noted. No study evaluated the effect of HPV DNA self-sampling on screening participation rates, early detection, survival, or quality of life.ConclusionsSelf-sampling for HPV DNA testing is a viable screening option, but there is insufficient evidence to conclude that self-sampling for HPV DNA testing is an alternative to the Pap test. Although HPV DNA testing using self-collected samples holds promise for use in under-resourced areas or for women who are reluctant to participate in Pap testing programs, the evidence supporting it is limited. Further definitive research is needed to provide a solid evidence base to inform the use of self-sampling for HPV DNA testing for the purpose of increasing screening rates, especially in women who are never or seldom screened.     

The combined impact of implementing HPV immunisation and primary HPV screening in New Zealand: Transitional and long-term benefits,costs and resource utilisation implications

BackgroundIn response to emergent evidence, many countries are transitioning from cytology-based to HPV screening. We evaluated the impact of an upcoming transition on health outcomes and resource utilisation in New Zealand.MethodsAn extensively validated model of HPV transmission, vaccination, natural history and cervical screening (‘Policy1-Cervix’) was utilised to simulate a transition from three-yearly cytology for women 20–69 years to five-yearly HPV screening with 16/18 genotyping for women 25–69 years, accounting for population growth and the impact of HPV immunisation. Cervical cancer rates, resources use (test volumes), costs, and test positivity rates from 2015 to 2035 were estimated.FindingsBy 2035, the transition to HPV screening will result in declines in cervical cancer incidence and mortality rates by 32% and 25%, respectively, compared to 2018. A potentially detectable 5% increase in cervical cancer incidence due to earlier detection is predicted for the year of transition. Annual numbers of women screened will fluctuate with the five-year screening interval. Cytology volumes will reduce by over 80% but colposcopy volumes will be similar to pre-transition rates, and program costs will be reduced by 16%. A 9% HPV test positivity rate is expected in the first round of HPV screening (2019–2023), with 2.7% of women referred for colposcopy. Transitioning from cytology to primary HPV cervical screening could avert 149 cancer cases and 45 deaths by 2035.ConclusionPrimary HPV screening and vaccination will reduce cervical cancer and resources use. A small transient apparent increase of invasive cancer rates due to earlier detection may be detectable at the population level, reflecting the introduction of a more sensitive screening test. These findings can be used to inform health services planning and public communications surrounding program implementation.     

Age-specific detection of high risk HPV DNA in cytologically normal, computer-imaged ThinPrep Pap samples

OBJECTIVE: Recent cervical cancer screening guidelines for women over age 30 seek to improve the sensitivity of cytology by incorporating high-risk (HR) human papillomavirus (HPV) DNA testing into the screening algorithm, a recommendation based largely on data that utilized the conventional Pap smear and were not stratified by patient age. Data on the rate of HR HPV among women over age 30 undergoing liquid-based Pap test screening are limited. The objective of this study was to determine the rate of HR HPV DNA positivity in women ages 30 and over with a cytologically negative liquid-based Pap test result. METHODS: Consecutive residual ThinPrep Pap samples from women with a cytologically negative result following computer-assisted screening were tested for HR HPV using the Hybrid Capture 2 (HC2) method. All HC2-positive samples were additionally tested with the Linear Array (LA) HPV Genotyping Test. RESULTS: 1000 cytologically negative specimens from women aged 30 to 45 years (38.9+/-4.7 years) were evaluated. The overall HC2 HR HPV positivity rate in this age group was 3.9% (confidence interval 2.8-5.3%). When stratified by age group, the rate was inversely proportional to age (ages 30-35: 6.7%; 36-40: 3.0%; 41-45: 2.6%) and lower than most previous reports (1-17%). Some of the cases that were positive for HR HPV by HC2 were negative by LA, or showed only low-risk virus. CONCLUSIONS: The HR HPV rates in women ages 30-45 with a cytologically negative, computer-imaged ThinPrep test result are low. If these findings are confirmed in future studies, the added benefit of HPV testing to liquid-based cytology for women ages 30 and over should be critically evaluated.     

HPV-Selbstuntersuchung

In Germany, less then 50% of the female population attends cervical cancer screening. Self-assessment for HPV offers more women the chance to participate in screening. The published studies have employed various collection devices. The use of tampons and vaginal lavage yielded an acceptable sensitivity for the detection of CIN and cervical cancer, however, has limited practicability. Vaginal self-sampling using a dacron-swab shows a high acceptance rate but heterogeneous results in the detection rate of cervical neoplasia. Vaginal self-sampling with a smooth and thin brush achieved the best results in acceptance rate and sensitivity. The sensitivity of HPV self-assessment is equal or better when compared to cytology, however, the false-positive rate is higher. For follow up of HPV positive women, colposcopic assessment is mandatory. Cytological controls are not sufficient. HPV self-assessment in non-gynaecological offices or even at home has the potential to increase the participation rate in countries with opportunistic screening of cervical cancer. However, current study data are limited. Therefore, implementation of HPV self-assessment cannot be recommended at the moment.     

Cribado de cáncer cervical con citología y test del virus del papiloma humano cada 5 años: una realidad

Objective

To analyze screening for cervical cancer with a combination of cytology and HPV testing in women older than 35 years every 5 years and to determine whether the application of this protocol delays diagnosis of cervical cancer.

Material and methods

Cervical cancer screening strategies have been applied in our hospital since 2005. HPV testing was introduced in 2010 for women older than 35 years. We performed a retrospective study of 500 women attended in our hospital. We studied whether we had correctly applied the strategy and the recommended time interval of the next review. We analyzed cervical cancers diagnosed in our hospital since 2005.

Results

The strategy was correctly applied in 100% of the women. Screening was performed with both cytology and HPV testing in 45.6% and with cytology alone in 23.2%; no screening was performed in 31.2%. The recommended interval until the next review was 5 years in 26% of the patients. The implementation of the strategy did not delay the diagnosis of cancer. Cervical cancer was diagnosed in 27 women since 2005. Only one woman with adenocarcinoma had been correctly screened (before the introduction of HPV testing). In the last 2 years, four microinvasive carcinomas were diagnosed with this strategy.

Conclusions

A combination of cytology and HPV testing can be applied in women older than 35 years and screening intervals can be increased to 5 years in routine clinical practice. This protocol does not delay the diagnosis of cervical cancer and optimizes resources by lengthening the interval between screening tests in healthy women.     

Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions

Background

Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples.

Purpose

To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation.

Methods

Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay.

Results

The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV).

Conclusions

High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.     

Accuracy of HPV testing of vaginal smear obtained with a novel self-sampling device

BACKGROUND: Most of women diagnosed as having cervical cancer have not participated in organized cytological screening. Aim. A study was conducted to evaluate the accuracy of human papilloma virus testing by self-collected vaginal samples in comparison to regular cytological screening. The agreement of hybrid capture 2 assay and polymerase chain reaction assay for detection of human papilloma virus DNA in self-collected vaginal samples and clinician-obtained cervical smears was investigated. METHOD: Forty-three women aged 23-58 years admitted for further examination due to previous positive cytology in the organized screening participated in self-collecting of vaginal samples with a novel self-sampling device. During the visit a clinician also collected a cervical smear using a cytobrush. The vaginal samples collected with the self-sampling device were analyzed for high-risk human papilloma virus with the hybrid capture 2 assay technique and the cervical smears were Pap-stained, examined cytologically and after that reanalyzed for human papilloma virus DNA using a polymerase chain reaction assay. RESULT: The vaginal samples were positive for high-risk human papilloma virus in 37% of the cases using hybrid capture 2 assay. Twelve of the 43 Pap smears showed positive cytology (ASCUS-CIN 3), of which 4 showed CIN 2-3. When polymerase chain reaction assay was performed, human papilloma virus DNA was detected in 40% of the glass slides. The agreement between cytology and the two human papilloma virus testing techniques was 67-74% (kappa 0.27-0.45) and the agreement between the two human papilloma virus tests was 70% (kappa 0.36). CONCLUSION: Testing for high-risk human papilloma virus can identify more women at risk of developing cervical cancer than cytology irrespective of the sampling method. Furthermore, offering a self-sampling device for collection of vaginal smear seems to be a useful screening tool for cervical cancer among women not responding to an invitation for smear sampling.     

Self-sampling experiences among non-attendees to cervical screening

ObjectiveHigh coverage and attendance is essential to positive cervical cancer screening results. Offering self-sampling for HPV-testing to the non-attendees of the program may improve attendance rates. Information on women's perceptions and experiences with self-sampling (acceptability) is needed to further optimize attendance by this method.MethodsA questionnaire study focusing on women's experiences on the screening method was embedded in a trial investigating the effects and feasibility of self-sampling among non-attendees of cervical screening in 31 Finnish municipalities in 2011–2012 (n = 4688). Reasons for non-attendance in routine screening were also surveyed.ResultsResponse rate to the questionnaire was 98.8% (909/920) among women who performed self-sampling. Self-sampling participants reported mainly good experiences. Negative experiences (difficulties in sample taking, pain, fear, anxiety, insecurity) were reported rarely, but more commonly among women with a mother tongue other than Finnish or Swedish (immigrants). Most common reason for non-attendance in routine screening was a recent Pap-smear elsewhere (opportunistic screening). Practical reasons (pregnancy, scheduling difficulties) were reported by 42%, emotional or attitudinal reasons by 17%, and 16% forgot to take part. Response yield to questionnaire was unsatisfactory among those women who declined the self-sampling option.ConclusionsOptimizing the practical aspects of screening and offering a self-sampling option to non-attendees can help to overcome a large variety of both practical and emotional barriers to traditional screening. More research is needed among the non-attendees to routine screening who decline also the self-sampling option.     

HPV testing in primary cervical screening: a systematic review and meta-analysis

ObjectivePrevious findings from cross-sectional studies have shown human papillomavirus (HPV) testing to be more sensitive than cytology testing for primary cervical screening. This systematic review aims to assess whether the increase in baseline detection with HPV testing corresponds to lower rates in subsequent screening rounds.MethodsWe searched Medline, EMBASE, and the Cochrane Library for randomized controlled trials (published from 2005 to 2010) comparing HPV-based and cytology-based cervical screening. Primary outcomes of interest were relative rates of higher grade cervical intraepithelial neoplasia and invasive cervical cancer. Secondary outcomes included test performance characteristics and colposcopy referral rates. Results were pooled where possible using a random effects model.ResultsSeven randomized trials were identified. Across studies, HPV testing was more accurate than conventional cytology and detected significantly more CIN3+ in the first screening round (Mantel-Haenszel [M-H] risk ratio 1.67; 95% CI 1.27 to 2.19) and significantly less in the second screening round (M-H RR 0.49; 95% CI 0.37 to 0.66). There were no differences in pooled rates of CIN2+ (M-H RR 1.19; 95% CI 0.94 to 1.50) and CIN3+ (M-H RR 1.09; 95% CI 0.84 to 1.42), but there was a higher pooled rate of CIN2 (M-H RR 1.37; 95% CI 1.12 to 1.68) over two screening rounds. A trend towards lower rates of invasive cervical cancer was observed.ConclusionOrganized screening programs in higher resource settings should consider adopting HPV testing as the primary screening test for women 30 or 35 years of age and older. Further research is needed to determine optimal screening strategies for younger women.     

Integrating HPV testing for primary screening?

Cervical cancer, the second most common cancer in young women in France, is still today imperfectly screened even with the advent of primary prevention for this cancer in the form of prophylactic HPV vaccination. Indeed, the cervical Pap smear and its cytologic analysis, both operator and reader dependent, have limited sensitivities requiring repeated samplings and above all, producing a high rate of falsely negative tests. Although most cancers occur in women who are either not or insufficiently screened, the problem with cervical smears is the fact that cancers are also often diagnosed in young women having follow-ups in accordance with professional guidelines. The absence of an organized screening in France results in an inadequate female population coverage. Nowadays, it is unanimously recognized that high-risk papillomaviruses (HR HPV) represent the only independent risk factor for cervical cancer and that there cannot be any disease without this virus. It is therefore this strong association between a viral agent and the cervical cancer which opened the door firstly, to the notion of prophylactic vaccination and secondly, to the integration of HR HPV testing in the screening for precancerous lesions. Molecular biological techniques based on the HR HPV genome detection within the female genital tract have shown a very high sensitivity without any inter and intraobserver variability and an excellent negative predictive value. Their integration in the primary screening for cervical cancer would improve the relevance of the latter and would suit the need for a wider population coverage and even for an organized screening thanks to the possibility for self-sampling. The specificity of these tests is inferior to that of the cervical smear, but the management of the falsely positive HPV tests has proved to be efficient by sorting residual cells obtained from liquid-based cytology. What is urgent in France is the need for an organized screening programme in order to improve population coverage and, this does not go against neither a vaccination promotion nor the integration of new technologies. Moreover, the last three randomized trials published in October 2007 have shown that it was quite safely possible to extend the time interval between two consecutive viral testing and thus improving the cost-effectiveness of cervical cancer screening. The aim of this work was to analyze publications on the subject in order to conclude, according to proof levels obtained by different studies, on its usefulness in the secondary prevention of cervical cancer.     

Attitudes to self-sampling of vaginal smear for human papilloma virus analysis among women not attending organized cytological screening

BACKGROUND: The major problem with the cytological screening is the non-optimal participation rate among women invited for cervical smear collection. The aim of the present investigation was to examine the attitudes of the non-responding women to perform self-sampling of vaginal smear at home as a method to increase the coverage of the screening and to examine the prevalence of high-risk human papilloma virus (HPV) among the responding women. METHODS: From the database of the Department of Cytology, University Hospital of Uppsala 198 women, aged 35-55 years, who had not attended the organized gynaecological screening for over 6 years were identified. They were sent a letter of information about the study and one week later a self-sampling device aimed to collect vaginal smear. The vaginal smear of the women responding to the offer of self-sampling was analysed for high-risk HPV using Hybrid Capture 2 method or polymerase chain reaction amplification of HPV DNA. All women in the study also received a questionnaire in order to investigate their attitudes towards self-sampling as an alternative in the organized screening. RESULTS: Of the 198 women 15 women had to be excluded. Fifty-eight per cent of the women responded and collected vaginal smear at home and among them 7% were positive for high-risk HPV. The questionnaire revealed no significant difference of age, country of birth and occupation or marital status, on using self-sampling of vaginal smear at home. The attitudes among responding and non-responding women differed. The responding women who contributed by sampling vaginal smear were more positive to self-sampling of vaginal smear (p<0.01). CONCLUSIONS: Offering self-sampling of vaginal smear in women not attending the organized cytological screening increases the coverage and identifies an additional group of women with an increased risk to develop cervical cancer. The attitude towards self-sampling was mainly positive.     

Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

贵州省三都水族自取样HPV检测宫颈癌筛查及分流模式#br#

Objective?To explore a cervical cancer screening strategy suitable for remote minority areas in China. Methods?A total of 1 874 cases of shui minority women aged 21~65 years in Sandu were randomly sampled self-sampling HPV test, TCT test and P16 cytological immunohistochemical test. The patients with HPV positive, TCT abnormality (ASC-US) and P16+underwent colposcopy and biopsy, and squamous intraepithelial lesion (SIL) was detected. Results?The positive rate of HR-HPV was 15.69% in 1 874 women. HPV52 was the most common type, followed by HPV16, HPV39, HPV58 and HPV56. Among 249 patients with colposcopy biopsy, 23 cases (9.24%) were detected with HSIL or above lesions.The positive rates of p16 in HSIL and above cervical lesions, LSIL and cervicitis were 73.91%, 34.57% and 10.34% (P<0.001).The sensitivity of self-sampled HPV test to HSIL+ was 100%, and the area under ROC curve for HSIL+ detected by HPV-positive test and p16 test was 0.577 (P>0.05) and 0.774 (P<0.05), respectively. Conclusion?Self-sampled HPV was highly sensitive to HSIL. Using self-sampling HPV detection as primary screening, combined with p16 staining triage, can be used as a screening strategy in remote areas of Guizhou province to improve the coverage of screening.     

HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3

Objective

To evaluate if women with HPV16 positive CIN2 and CIN3 are diagnosed at a younger age.

Methods

We conducted a population-based cohort study including more than 40,000 women having a liquid based cervical cytology sample taken as part of routine screening. HPV analysis was performed using Hybrid Capture 2 and LiPAv2. The study population was linked to the Danish Pathology Data Bank to retrieve information on subsequent cervical histology. We included HR HPV positive CIN2/3 samples, comprising 173 CIN2 and 467 CIN3 lesions. Due to a high number of multiple concurrent HPV infections, the causative HPV type was assigned to a hierarchically group.

Results

In CIN3, the estimated proportion of lesions positive for HPV16 was 68.1% among women aged 20 years and decreased to 38.9% among women aged 50 years. A decrease in HPV16 positivity with increasing age was also observed in CIN2. In a multinomial logistic regression analysis, young age was strongly associated with HPV16 positivity in CIN3 lesions (OR = 0.46 per 10 year increase in age, 95% CI: 0.32-0.65). The proportion of HPV16 and/or 18 positive lesions among women diagnosed with CIN2 and CIN3 below 30 years of age was 44% and 75%, respectively.

Conclusions

HPV16 positivity was significantly associated with younger age at diagnosis of CIN3. In a population vaccinated against HPV16 and 18, we will experience a shift to older ages in cervical precancerous lesions. These findings may imply that cervical cancer screening programs could start at an older age in HPV vaccinated populations.     

Performance of the Roche AMPLICOR human papillomavirus (HPV) test in prediction of cervical intraepithelial neoplasia (CIN) in women with abnormal PAP smear

OBJECTIVES: To assess the performance of a novel PCR-based assay (Roche AMPLICOR HPV test) in detection of cervical pathology as a part of management for abnormal PAP smear (MAPS) and in women participating in cervical cancer screening. STUDY DESIGN: Altogether, 504 women comprising 270 patients referred for colposcopy due to an abnormal Pap smear and another 234 women participating in cervical cancer screening (tested for comparison) were analyzed for oncogenic (HR) Human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 using the Roche AMPLICOR HPV test in cervical samples collected in PreservCyt liquid media. Colposcopic biopsy and/or LEEP cone biopsy was used as the gold standard in the triage group, while liquid-based cytology (LBC) was the reference test in the screening group. RESULTS: The prevalence of HPV was significantly higher in the MAPS group (65.9%) than in the screening group (31.2%) (P = 0.0001). There was a poor concordance between the referral PAP and the current LBC, being only moderate in the screening series, ICC (weighted kappa) = 0.291 (95%CI 0.070-0.459) (P = 0.007), and almost poor in the MAPS Series, with ICC = 0.217 (95%CI 0.04-0.384) (P = 0.023). AMPLICOR HPV positivity increased linearly with the increasing grade of cervical lesions. In detecting high-grade (CIN2-3), colposcopy was the most sensitive test (96.5%), very similar to AMPLICOR (95.2%) (P = 0.731), while LBC with HSIL cutoff was by far the most specific test (99.5%) and showed the highest PPV (96.1%). NPV of colposcopy (97.2%) and AMPLICOR (96.7%) were similar (P = 0.839). Together with abnormal colposcopy and HSIL cytology, the AMPLICOR HPV test is a powerful independent predictor of high-grade CIN2-3, and as such suitable to replace cervical cytology in management of women with abnormal PAP test (MAPS). CONCLUSIONS: The Roche AMPLICOR HPV test is comparable to other HPV tests (HCII, PCR) in detecting CIN in MAPS. However, more data are clearly needed on the performance of AMPLICOR test in management of abnormal PAP and particularly as a screening tool.     

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

IntroductionIn 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.ObjectiveTo determine the prevalence of high-risk HPV 16/18 DNA in women with abnormal cervical cytology.Subjects and methods45 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.Results45 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.ConclusionThe 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.     

Epidemiology of cervical cancer and human papilloma virus infection among Iranian women — Analyses of national data and systematic review of the literature

BackgroundFew studies have evaluated the epidemiology of cervical cancer in low risk Muslim countries, where the prognosis of cervical cancer is poor and which lack an organized cervical screening program. We studied incidence and mortality rates of cervical cancer and the prevalence of high risk human papilloma virus (HPV) infection in the Islamic Republic (I.R.) of Iran.MethodsWe analyzed national cancer and mortality registration data and estimated age-standardized incidence (ASR) and mortality (ASMR) rates and age-specific patterns of cervical cancer. Furthermore, based on a systematic review we estimated prevalence of HPV infection in Iran.ResultsThe mean cervical cancer ASR was 2.5 per 100,000 in pathology-based cancer registries. However, ASRs were almost double in the population-based cancer registry and reached 6 per 100,000. The mean cervical cancer ASMR for Iran was 1.04 per 100,000. The mortality to incidence ratio was 42%. The cervical cancer incidence rate increased after age 30 and peaked between ages 55 and 65. The prevalence of HPV infection was 76% in cervical cancer patients and 7% among healthy Iranian women. Of the HPV types isolated, HPV 16 (54%), 18 (14%), and 31 (6%) were the most commonly detected in Iranian cervical cancer patients.ConclusionsAn organized prevention program is needed to fight against cervical cancer in Iran and other low incidence countries. We suggest a screening program starting after age 30 and with at least three screenings tests over each woman's lifetime. With a reservation on cost-effectiveness issue, available HPV vaccine will prevent HPV infection and cervical cancer in Iran.     

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer

OBJECTIVE: To evaluate new techniques in primary cervical cancer screening programmes. DESIGN: Cross sectional pilot study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital. POPULATION: Consecutive 2032 human papillomavirus (HPV) DNA and Pap smear samples were taken. Histological diagnoses were obtained from 460 patients. METHODS: We compared the validity of the high risk (HR) HPV DNA detection test to automation-assisted and conventional Pap smear screening. MAIN OUTCOME MEASURES: Specificity and sensitivity of screening methods. RESULTS: Twenty-three percent of women were HPV positive. Forty-five of 46 had high grade lesions and cancers were HR HPV DNA positive, whereas 72/93 of low grade and more severe lesions were HR HPV DNA positive. When histologically verified high grade lesions were observed, the relative sensitivity of HR Hybrid Capture 2 (HR HC2) test was 98% compared with conventional Pap smear and Papnet tests, which performed 54%versus 58%, 83%versus 86% and 93%versus 98% relative sensitivity respectively, using cytological diagnoses HSIL (high grade squamous intraepithelial lesion), LSIL (low grade squamous intraepithelial lesion) or ASCUS (atypical squamous cells of undetermined significance) as the cutoff. The specificity of HC2 test (77-79%) was comparable with the ASCUS+ (ASCUS and more severe) cytology (68-79%), but lower when compared with LSIL+ (91-95%) or especially HSIL+ (97-99%) Pap smear results. CONCLUSION: Pap smear, as a screening test, is very different from HPV DNA detecting test HR HC 2. If cutoff LSIL or more severe lesions is used, primary Pap smear is clearly more specific than HR HC2, but markedly less sensitive. Due to high relative sensitivity of the HPV, only very few histologically confirmed high grade lesions would be detected among HPV negatives using simultaneous cytology. On the other hand, using HPV DNA test alone would lead to multifold amounts of referrals for colposcopy. A posterior Pap smear assessment among HPV positives might be helpful in increasing sensitivity and specificity of screening and defining those who need an immediate referral or treatment. We plan to incorporate primary HR HPV DNA test with posterior Pap smear reading of HPV positives into our ongoing randomised prospective multiarm trial evaluating new techniques in organised screening for cervical cancer in Finland.     

Epidemiological study in Okinawa, Japan, of human papillomavirus infection of the uterine cervix

OBJECTIVE: To investigate the prevalence and type distribution of human papillomavirus (HPV) in women with normal cervical cytology and with cervical intraepithelial neoplasia I to III(CIN) or carcinoma of the cervix in Okinawa, Japan. METHODS: We investigated HPV DNA in 4,078 subjects with cytologically normal cervices, 279 subjects with CIN, and 383 subjects with cervical cancer in Okinawa Prefecture in Japan. The presence of HPV DNA was also compared among generations. HPV DNA was both detected and typed using polymerase chain reaction (PCR). RESULTS: The HPV positivity rate was 10.6% in the subjects who were normal on cervical cytodiagnosis. In each generation, the positivity rate was 20.4% in women aged 20-29 years and approximately 10% in the groups aged 30-89 years, with significant differences among generations. The HPV positivity rates in CIN and cervical cancer groups were 76.0% and 86.2%, respectively, with no significant difference between the groups. The positivity rate of HPV 16 decreased with age in both CIN and cervical cancer groups. CONCLUSION: Among non-cancer subjects, HPV infection rates were almost 20% in women aged 20-29 years and 10% in women aged 30-89 years. HPV16-positive CIN or carcinoma were more prevalent in the younger women, suggesting that HPV16-infected epithelial cells rapidly progress to cervical cancer.