Routine Cervical Screening Research Articles

What investigations are needed to optimally monitor for malignancies in SLE?

The overall cancer incidence risk in systemic lupus erythematosus (SLE) is approximately 15%-20% more than in the general population. Nevertheless, to date, the optimal malignancy screening measures in SLE remain undefined. Our objective is to determine what investigations are needed to optimally monitor for malignancies in SLE in order to inform upcoming Canadian Rheumatology Association recommendations. We conducted a systematic search looking at three scientific sources, Embase, Medline and Cochrane, in an attempt to identify cancer screening recommendations for patients with SLE. We used a filter for observational studies and included articles published in 2000 and onward. The initial search strategy led to 986 records. After removal of duplicates and articles unrelated to SLE, we were left with 497 titles. From those, 79 research articles on cancer incidence in SLE were isolated and reviewed. Of the 79 original research papers, 25 offered screening recommendations, 14 suggested additional cancer screening whereas 11 studies simply promoted adherence to general population screening measures. The suggestions for more rigorous screening included recommending human papilloma virus testing in addition to routine cervical screening, and/or that cervical screening should be performed annually and/or suggested urine cancer screening in SLE patients with a history of cyclophosphamide exposure. We found no original research studies directly comparing cancer screening strategies in SLE. Generally, authors recommend adherence to general population screening measures, particularly cervical screening. This, possibly with adding targeted screening in special cases (e.g. annual urine cytology in patients with prior cyclophosphamide exposure, and considering existing lung cancer screening guidelines for past heavy smokers), may be a reasonable approach for cancer screening in SLE.

An epidemiological study assessing the prevalence of human papillomavirus types in women in the Kingdom of Bahrain.

BackgroundPersistent infection with high-risk (HR) human papillomavirus (HPV) causes cervical cancer, the fourth most frequent cancer in the Kingdom of Bahrain, with an annual incidence of four per 100,000 women. The aim of this study was to assess the prevalence and type distribution of HPV in Bahraini and non-Bahraini women attending routine screening. HPV prevalence was assessed by risk factors and age distribution. Health-related behaviors and HPV awareness were also studied.MethodsThis observational study was conducted between October 2010 and November 2011 in the Kingdom of Bahrain (NCT01205412). Women aged either ≥20 years attending out-patient health services for routine cervical screening or ≥16 years attending post-natal check-ups were enrolled. Cervical samples were collected and tested for HPV-DNA by polymerase chain reaction and typed using the SPF10 DEIA/LiPA25 system. All women completed two questionnaires on health-related behavior (education level, age at first marriage, number of marital partners, parity and smoking status) and HPV infection awareness.ResultsHPV DNA was detected in 56 of the 571 women included in the final analysis (9.8%); 28 (4.9%), 15 (2.6%) and 13 (2.3%) women were infected with single, multiple and unidentifiable HPV types, respectively. The most prevalent HPV types among the HPV positive women were HR-HPV-52 in eight (1.4%), HR-HPV-16, -31 and -51 in six women each (1.1%); low-risk (LR)-HPV-6 in four (0.7%); and LR-HPV-70, -74 in three women each (0.5%). Co-infection with other HR-HPV types was observed in 50% HPV-16-positive women (with HPV-31, -45 and -56) and in both HPV-18-positive women (with HPV-52). None of the health-related risk factors studied were associated with any HR-HPV infection. More than half of women (68.7%) had never heard about HPV, but most women (91.3%) in our study were interested in HPV-vaccination.ConclusionHPV prevalence in Bahraini women was 9.8%. The most frequently observed HPV types were HR-HPV-52, -16, -31 and -51 and LR-HPV-6, -70 and -74. These are useful baseline data for health authorities to determine the potential impact of preventive measures including the use of prophylactic vaccines to reduce the burden of cervical cancer.

Association between second-trimester cervical length and cesarean delivery in multiparas.

The purpose of this study was to determine whether there is an association between second-trimester cervical length and cesarean delivery in women with a prior vaginal delivery. We conducted a retrospective cohort study of multiparous women with singleton gestations who underwent routine cervical length screening between 18 and 24 weeks' gestation and labored after 34 weeks. Cervical lengths were divided into quartiles, and the frequency of cesarean delivery was compared across the groups. Indications for cesarean delivery were also compared. A multivariable logistic regression was performed with cervical length as a categorical and a continuous variable to adjust for potential confounders. Of the 2260 multiparas who met inclusion criteria, 63 (2.8%) underwent a cesarean delivery. We observed no association between the second-trimester cervical length quartile and the frequency of cesarean delivery (2.1%, 3.5%, 2.3%, and 3.1%, respectively; P = .434). Further analysis using cervical length as a continuous variable and controlling for potential confounding variables did not change this result (adjusted odds ratio, 1.08; 95% confidence interval, 0.80-1.46). The second-trimester cervical length quartile in multiparas is not associated with an increased frequency of cesarean delivery. This finding differs from studies of nulliparas.

HPV genotype prevalence in Australian women undergoing routine cervical screening by cytology status prior to implementation of an HPV vaccination program

BackgroundData on the prevalence of cervical HPV genotypes in Australia by age and by grade of cytological abnormality are sparse. ObjectiveMeasure prevalence of HPV genotypes among 2620 Australian women by age and cytology status. Study designWomen presenting for routine Pap smear screening were recruited from diverse regions, including a significant sample of Indigenous women. DNA extracts prepared from Thinprep specimens were HPV genotyped by Roche LINEAR ARRAY HPV. ResultsHPV prevalence and genotype distribution were stratified by age (mean 32.6y) and Pap smear result (cytology normal in 86.7%). Overall HPV prevalence was 38.7% with high-risk HPV prevalence of 26.5%. Prevalence of HPV (66.3% in women<21y to 15.3% in women>40y), multiple HPV infection (45.5% in <21y to 5.8% in >40y) and vaccine-targeted genotypes (HPV 6/11/16/18) (34.1% in <21y to 2.4% in >40y) declined significantly with age. The six most common genotypes were: HPV 16 (8.3%), 51 (5.1%), 53 (4.7%), 62 (4.3%), 89 (3.9%) and 52 (3.8%). HR-HPV prevalence increased from 21.1% in women with normal cytology to 80.9% in those with cytologically predicted high-grade abnormalities (HGAs) (p<0.001). The most common genotypes in women with HGAs were HPV 16 (51.1%), 18 (14.9%), 52 (12.8%), 31 (10.6%), and 33 (10.6%): all HR-types. ConclusionPre-vaccination cross-sectional prevalence of HR-HPV infection was high in this sample of Australian women attending for screening. HPV 16 was the commonest high-risk type detected at all ages and cytological grades.

Risk of cervical cancer associated with HPV infection among the gynae outdoor patients

Human papilloma virus is an oncogenic DNA virus, which is identified in 99.7% case of invasive cancer. It is the most prevalent virus involved in sexually transmitted diseases worldwide and an important public health challenge for the prevention of cervical carcinoma. Cervical cancer is the second cause of malignant neoplasia and death in women. The present study was thus designed to detect the risk factors for HPV infection in normal and unhealthy cervix of women attending tertiary care hospital (BSMMU). HPV DNA was detected among the study population using the Hybrid Capture 2 assay, which determined HPV high risk types. A total of 68 women between 25-70 years of age were included in this cross sectional study. Among them 13 (19.1%) cases were tested positive for HPV DNA. The risk factors for HPV infection identified from this result are early sexual activity, lower level of education, early marriage, multi-parity, total duration of sexual activity in years and long term use of oral contraceptive pill and poor socioeconomic condition. Increased awareness and understanding regarding HPV infection would improve the risk of infection and control in sexually active women. HPV diagnosis at early stages of infection is of fundamental importance. The use of HPV test in routine cervical mass screening may not be possible in developing countries like Bangladesh due to its high cost. Nevertheless, it has been shown to be a useful tool when combined with cytology to diagnose high-risk infection in apparently normal tissues, and may help to reduce the risk of cervical cancers. The results obtained from this study ultimately contribute to cervical cancer prevention among Bangladeshi women. DOI: http://dx.doi.org/10.3329/bmjk.v46i1-2.18231 Bang Med J (Khulna) 2013; 46 : 3-6

Detection of Human Papillomavirus DNA in Routine Cervical Scraping Samples: Use for a National Cervical Cancer Screening Program in a Developing Nation

Human papillomavirus is a well-established cause of the development of a variety of epithelial lesions in the cervix. However, as yet, incorporation of HPV testing into cervical cancer screening either as an adjunct or stand alone test is limited due to its cost. We therefore here ascertained the presence and type specificity of human papilloma virus (HPV) DNA in routine cervical scrapings. Cervical scrapings were collected from women attending clinics for routine Pap smear screening. HPV-DNA was detected by PCR using MY09/11 and GP5+/GP6+ primer sets and genotyping was accomplished by cycle-sequencing. A total of 635 women were recruited into the study with mean ± SD age of 43 ± 10.5 years. Of these 92.6% (588/635) were reported as within normal limits (WNL) on cytology. The presence of HPV infection detected by nested MY/GP+-PCR was 4.4% (28/635). The overall prevalence of high-risk HPV (HR-HPV) in abnormal Pap smears was 53.8% (7/13). HPVs were also seen in 3.1% (18/588) of smears reported as WNL by cytology and 5.9% (2/34) in smears unsatisfactory for evaluation. The overall percentage of HPV positivity in routine cervical screening samples is comparable with abnormal findings in cytology. Conventional Pap smear 'missed' a few samples. Since HPV testing is expensive, our results may provide valuable information for strategising implementation of effective cervical cancer screening in a country with limited resources like Malaysia. If Pap smear coverage could be improved, HPV testing could be used as an adjunct method on cases with ambiguous diagnoses.

Disagreement between Human Papillomavirus Assays: An Unexpected Challenge for the Choice of an Assay in Primary Cervical Screening

We aimed to determine the disagreement in primary cervical screening between four human papillomavirus assays: Hybrid Capture 2, cobas, CLART, and APTIMA. Material from 5,064 SurePath samples of women participating in routine cervical screening in Copenhagen, Denmark, was tested with the four assays. Positive agreement between the assays was measured as the conditional probability that the results of all compared assays were positive given that at least one assay returned a positive result. Of all 5,064 samples, 1,679 (33.2%) tested positive on at least one of the assays. Among these, 41% tested positive on all four. Agreement was lower in women aged ≥30 years (30%, vs. 49% at <30 years), in primary screening samples (29%, vs. 38% in follow-up samples), and in women with concurrent normal cytology (22%, vs. 68% with abnormal cytology). Among primary screening samples from women aged 30–65 years (n = 2,881), 23% tested positive on at least one assay, and 42 to 58% of these showed positive agreement on any compared pair of the assays. While 4% of primary screening samples showed abnormal cytology, 6 to 10% were discordant on any pair of assays. A literature review corroborated our findings of considerable disagreement between human papillomavirus assays. This suggested that the extent of disagreement in primary screening is neither population- nor storage media-specific, leaving assay design differences as the most probable cause. The substantially different selection of women testing positive on the various human papillomavirus assays represents an unexpected challenge for the choice of an assay in primary cervical screening, and for follow up of in particular HPV positive/cytology normal women.

UK population based study to predict impact of HPV vaccination

BackgroundIn 2008 a human papillomavirus (HPV) vaccination programme for cervical cancer prevention was implemented in the UK. Surveillance of vaccine uptake, impact on prevalence of HPV infection and cervical cancer incidence were identified as key measures to evaluate the intervention. ObjectiveTo determine baseline HPV prevalence in unvaccinated women and predict impact of HPV vaccination on high-grade cervical disease (CIN2+). Study designA pseudo-anonymous prospective cohort was sampled on entry to the routine cervical screening programme between March 2009 and November 2010. In total, 13,306 eligible females were identified and high-risk (hrHPV) type specific status determined. Potential impact of prophylactic vaccination on CIN2+ was calculated by applying HPV vaccine clinical trial data to the baseline HPV type-specific data. ResultsOf 13,306 samples tested, 3545 (26.6%) were confirmed positive for at least one hrHPV type and 1325 (10%) were positive for low risk HPV. HPV16 was the predominant type detected in cases positive with either single or multiple hrHPV infection(s) (5.2% and 4.7%, respectively). Based on hrHPV type-specific data, Gardasil would have prevented 33.2% HPV16/18 unrelated CIN2+ compared to 47.1% for Cervarix. This difference was not statistically significant. ConclusionPrior to the introduction of the HPV vaccine, approximately one-quarter of young women were positive for hrHPV and one-tenth positive for HPV16. Post-vaccination, we anticipate a substantial absolute risk reduction in high-grade cervical disease associated with both targeted and non-targeted hrHPV types. There is no significant difference between the two commercially available vaccines in terms of clinical impact.

Association Between Second-Trimester Cervical Length and Primary Cesarean Delivery

To evaluate whether an increased ultrasonographic cervical length in the second trimester is associated with an increased frequency of cesarean delivery. This is a retrospective cohort study of nulliparous women with a singleton pregnancy who underwent routine cervical length screening between 16 and 24 weeks of gestation and labored after 34 weeks of gestation at a single tertiary care hospital. Women were grouped by cervical length quartile, and the association between cervical length quartile and cesarean delivery was determined in both univariable and multivariable analyses. For every additional centimeter of cervical length, the odds of cesarean delivery increased by 20.3%. Similarly, the frequency of cesarean delivery increased with increasing second-trimester cervical length quartiles (17.4%, 22.3%, 21.8%, 27.7%; P<.001). This association persisted in multivariable analyses that included gestational age at delivery and induction of labor. This increased risk of cesarean delivery was primarily the result of women with arrest disorders in the first stage of labor (P<.001). Increased second-trimester cervical length quartile is associated with an increased frequency of primary cesarean delivery in nulliparous women. : II.

Routine cervical length and fetal fibronectin screening in asymptomatic twin pregnancies: is there clinical benefit?

Objective: To determine whether routine cervical length (CL) and fetal fibronectin (fFN) screening is associated with improved clinical outcomes in asymptomatic patients with twin pregnancies.Study design: We compared outcomes between two large cohorts of twin pregnancies who delivered in New York City from 2003 to 2012. One cohort (n = 532) was managed by a single group practice, delivered at one large academic medical center, and underwent routine serial CL and fFN screening. The second cohort (n = 456) delivered at a second large academic center and only underwent CL and fFN testing as clinically indicated. Outcomes measured include cerclage placement, preterm birth (PTB), spontaneous PTB (sPTB), and antenatal corticosteroid (ACS) exposure.Results: Rates of cerclage placement, PTB, and SPTB were similar between the two groups. However, routine CL and fFN screening was associated with improved rates of ACS exposure in patients who delivered <34 weeks (91.3% versus 74.7%, p = 0.005) and 34–36 6/7 weeks (41.3% versus 13.9%, p < 0.001) without increased ACS exposure in women who delivered at term. In patients who delivered <34 weeks, routine CL and fFN screening was significantly associated with improved rates of ACS exposure within 1–14 days of delivery and within 1–7 days of delivery.Conclusion: In twin pregnancies, routine CL and fFN screening does not reduce the risk of PTB or SPTB. However, the routine use of these tests is associated with significantly improved ACS exposure and timing for women who deliver preterm without increasing ACS exposure to women who deliver at term.

Macroscopically detected female genital injury after consensual and non-consensual vaginal penetration: A prospective comparison study

ObjectiveThe aim of this study was to compare the prevalence, type and pattern of macroscopically detected female genital injury after consensual and non-consensual vaginal penetration to further an understanding of the forensic significance of genital injury in women reporting sexual assault. A secondary aim was to identify any effect of a range of possible variables upon the likelihood of genital injury resulting from vaginal penetrative sexual intercourse. Study designTwo groups of reproductive age women (aged 18–45 years) were prospectively recruited within 72 h of a single episode of vaginal penetrative sex, and macroscopically examined for the presence of bruises, abrasions and lacerations at twelve external and internal genital sites. Forty one women who presented for forensic examination after reporting a sexual assault to police were recruited to the non-consensual group and 81 women who presented for routine cervical screening or with sexual health concerns to a primary health care service to the consensual group. Each group was examined by a different group of doctors, all of whom were experienced in both forensic genital examination and gynaecological examination of healthy and diseased sexually active women. Data collection and examination protocols were the same for both groups. ResultsThe key finding was a statistically significant difference in genital injury prevalence between women who were vaginally penetrated non-consensually and consensually; 53.7% of the non-consensual group (22/41) and 9.9% of the consensual group (8/81) were found to have at least one genital injury [OR 10.57, CI (4.07, 27.42), p < 0.00001]. Penetration with finger/s and possible pre-existing genital ‘infection’ were found to be significantly associated with the presence of injury in the univariate analysis after adjusting for consent. Logistic regression demonstrated that women penetrated without consent were 19.5 times more likely to sustain at least one genital injury, than those penetrated consensually [OR 19.53, CI (6.03, 63.24)] and that a penetration scenario that included finger/s was 4.2 times more likely to result in at least one genital injury than penetration without finger involvement [OR 4.25, CI (1.42, 12.78)], when controlling for other variables in the model. Whilst a comparatively low injury prevalence in the consensual group limited interpretation, results revealed possible differences in genital injury typology and pattern resulting from non-consensual and consensual vaginal penetration. Lacerations were seen after both consensual and non-consensual vaginal penetration, while abrasions and bruises were seen exclusively in the non-consensual group. ConclusionThis study demonstrated a significant consent group difference in genital injury prevalence and the highest macroscopically detected genital injury prevalence rate resulting from non-consensual vaginal penetration identified to date. Results also indicate that vaginal penetration with finger/s increases the likelihood of sex-related injury. The difference in type of injury sustained as a result of non-consensual and consensual vaginal penetration was an unexpected finding, and warrants further investigation. These results highlight the importance of a standardised means of detecting genital injury based on consistent injury definitions, examination protocols, and examiner experience and suggest that macroscopic genital examination may be uniquely placed to detect consent group differences in injury typology and pattern if they exist.

HPV Direct Flow CHIP: A new human papillomavirus genotyping method based on direct PCR from crude-cell extracts

HPV Direct Flow CHIP is a newly developed test for identifying 18 high-risk and 18 low-risk human papillomavirus (HPV) genotypes. It is based on direct PCR from crude-cell extracts, automatic flow-through hybridization, and colorimetric detection. The aim of this study was to evaluate the performance of HPV Direct Flow CHIP in the analysis of 947 samples from routine cervical screening or the follow-up of abnormal Pap smears. The specimens were dry swab samples, liquid-based cytology samples, or formalin-fixed paraffin-embedded tissues. The genotype distribution was in agreement with known epidemiological data for the Spanish population. Three different subgroups of the samples were also tested by Linear Array (LA) HPV Genotyping Test (n=108), CLART HPV2 (n=82), or Digene Hybrid Capture 2 (HC2) HPV DNA Test (n=101). HPV positivity was 73.6% by HPV Direct Flow CHIP versus 67% by LA, 65.9% by HPV Direct Flow CHIP versus 59.8% by CLART, and 62.4% by HPV Direct Flow CHIP versus 42.6% by HC2. HPV Direct Flow CHIP showed a positive agreement of 88.6% with LA (k=0.798), 87.3% with CLART (k=0.818), and 68.2% with HC2 (k=0.618). In conclusion, HPV Direct Flow CHIP results were comparable with those of the other methods tested. Although further investigation is needed to compare the performance of this new test with a gold-standard reference method, these preliminary findings evidence the potential value of HPV Direct Flow CHIP in HPV vaccinology and epidemiology studies.

Viral Load of High-Risk Human Papillomaviruses as Reliable Clinical Predictor for the Presence of Cervical Lesions

Infections with high-risk human papillomaviruses (Hr-HPV) can cause malignant transformation of the human cervical epithelium. HPV DNA tests generally are very sensitive to detect cervical neoplastic lesions but also identify transient HPV infections. As a consequence, the specificity and positive predictive value are low. We analyzed viral load of Hr- and possibly Hr-HPV types more than seven orders of magnitude (on a log10 scale) in 999 consecutive BD-SurePath liquid-based cervical cytology samples from routine cervical screening enriched with atypical squamous cells of undetermined significance (n = 100), low-grade squamous intraepithelial lesions (LSIL; n = 100), and high-grade squamous intraepithelial lesions (HSIL; n = 97) using type-specific multiplex quantitative real-time PCR and the BSGP5+/6+-PCR/MPG assay. In the 36-month follow-up, 79 histologically verified CIN2+ and 797 double-negative cytology cases were identified. Viral loads in LSIL and HSIL were significantly increased compared with no intraepithelial lesion or malignancy in both the quantitative PCR (qPCR) and BSGP5+/6+-PCR/MPG assay (P < 0.0001). The mean viral loads in LSIL and HSIL were not significantly different. Using a newly determined high viral load cut off for 14 Hr-HPV types, the sensitivity for prevalent CIN3+ remained at 100% for both assays compared with the minimal detection threshold. The specificity (corresponding to double-negative cytology at subsequent screening episodes) increased substantially (qPCR, from 91.1% to 95.7%; BSGP5+/6+-PCR/MPG, from 79.8% to 96.2%). Compared with DNA positivity alone, high Hr-HPV viral loads could reduce the amount of false positive results detected by the BSGP5+/6+-PCR/MPG and qPCR by 81.4% and 52.1%, respectively. Quantitative type-specific HPV DNA assays show high flexibility in defining thresholds that allow optimizing clinical accuracy for cervical cancer precursors.

Cervical smear cytology on routine screening in a semi urban population in New Delhi: A review of 610 cases

Background: Cervical cancer is an important public health problem among adult women in many developing countries. Cervical cytology became the standard screening test for cervical cancer and premalignant cervical lesions with the introduction of the Papanicolau (Pap) smear. The most widely used system for describing PAP smear result is the Bethesda System 2001. Material and Methods: This study was aimed at evaluating the entire spectrum of types and frequencies of cervical cytological abnormalities i.e. infective, pre-cancerous and cancerous, in women who underwent routine cytological cervical screening at our hospital which caters largely to women of low socio-economic status. Results: A total of 610 cases of cervical pap smears were received in our cytology laboratory during this two year period, 348(57%) abnormal Pap smears, and 238(39%) cases which were normal. Out of the 348 cases, 306(50.2%) cases were reported to have inflammatory/reactive/reparative changes whereas epithelial cell abnormality was reported in 42 cases. Discussion: Cervical smear cytology also plays an important role in the diagnosis of cervical infections which are common in women of the reproductive age group. Conclusion: Hence, the need of the hour is an effective screening programme that is based on available resources and is readily available to the low socio-economic and disadvantaged sections of our society.

527: Routine cervical length and fetal fibronectin screening in asymptomatic twin pregnancies: is there clinical benefit?

Twin gestations are at an increased risk of preterm birth (PTB). A short cervical length (CL) and a positive fetal fibronectin (fFN) are both significantly associated with PTB in twin pregnancies. However, it is uncertain if the routine use of these screening tests in asymptomatic twin pregnancies leads to improved outcomes. Our objective was to assess whether routine CL and fFN screening in twin gestations is associated with improved outcomes.

Development of a pre-notification leaflet to encourage uptake of cervical screening at first invitation: a qualitative study

Cervical screening attendance among women aged 25-29 years in England is lower than at older ages. There is some evidence that pre-notification leaflets motivate women who have not yet considered their response to a health intervention. We aimed to identify key information to motivate young women at their first cervical screening invitation. Six focus groups were conducted, five with young women aged 17-25 registered with a General Practice in Manchester, UK, and one with Practice nurses. Some women took part in two further groups to discuss leaflet design. There was low awareness of the purpose or procedures of cervical screening, and most women were de-motivated by reports of bad experiences. Some intended to be screened, but not immediately after invitation. Screening was viewed as a test for a cancer that affected older women. Since none of the participants believed that they had cervical cancer, screening seemed unnecessary. We conclude that the perception that screening is unimportant when you are young needs to be challenged. Women also need to be better informed of screening procedures. A pre-notification leaflet incorporating key information was designed and will be tested in a randomized trial of complex interventions within the routine cervical screening programme.

Acceptance of and attitudes towards human papillomavirus vaccination in Japanese mothers of adolescent girls

To better understand how to achieve high uptake rates of human papillomavirus (HPV) vaccination in Japan, we investigated acceptance of and attitudes towards HPV vaccination in 2192 mothers of girls aged 11–14yrs. A school-based survey was conducted in five elementary and fourteen junior high schools in Sapporo, Japan. Responses from 862 participants were analyzed. Ninety-three percent of mothers would accept the vaccine for their daughter if free, but only 1.5% was willing to pay the minimum recommended price of ¥40,000. Vaccine acceptance was higher in mothers who had heard of HPV vaccine (adjusted odds ratio, aOR=2.58, confidence interval, CI=1.47–4.53), and who believed susceptibility to (aOR=2.30, CI=1.34–3.92) and severity of (aOR=3.73, CI=1.41–9.88) HPV to be high. Recommendations from a doctor (aOR=12.60, CI=7.06–21.48) and local health board (aOR=27.80, CI=13.88–55.86) were also positively associated with increased HPV vaccine acceptance. Concerns about side effects of both the HPV vaccine (aOR=0.03, CI=0.01–0.08) and routine childhood vaccines in general (aOR=0.11, CI=0.02–0.78) emerged as barriers to vaccination. Not participating in routine cervical screening also emerged as a deterrent (aOR=0.49, CI=0.27–0.91). While most mothers (66.8%) agreed that 10–14yr was an appropriate age for vaccination, a further 30.6% believed >15yr to be more appropriate.In conclusion, attitudes of Japanese mothers toward HPV vaccination are encouraging. While lower vaccine acceptance in mothers who do not undergo regular cervical screening needs further investigation, this study indicates that high uptake may be possible in a publically funded HPV vaccination program if physicians actively address safety concerns and justify why the vaccine is needed at a particular age.

Brush-based self-sampling in combination with GP5+/6+-PCR-based hrHPV testing: High concordance with physician-taken cervical scrapes for HPV genotyping and detection of high-grade CIN

BackgroundStudies have shown that self-sampling for hrHPV testing (HPV self-sampling) is highly acceptable to women, increases screening participation rate, and may therefore further reduce cervical cancer incidence. However, it is important to clinically validate HPV self-sampling procedures for screening purposes. ObjectivesClinical validation of combined brush-based self-sampling with GP5+/6+-PCR EIA for primary cervical screening. In addition, HPV type-specific agreement between sample types and acceptability of brush-based self-sampling were evaluated. Study design135 women referred for colposcopy took a self-sample at home prior to vaginal- and cervical sampling by a gynaecologist. All women were biopsied for histology. HPV testing was done by GP5+/6+-PCR EIA, with genotyping by reverse line blotting (RLB). Acceptability of sampling methods was measured with a questionnaire. ResultsIn this outpatient population, hrHPV test results showed good concordance between self-samples and physician-taken cervical scrapes (86%, k=0.70), with sensitivities and specificities for CIN2+ that did not differ significantly (93% and 51%, 91% and 51%, respectively (P=1.0)). The clinical sensitivity of brush-based self-sampling combined with GP5+/6+-PCR EIA hrHPV testing for detection of CIN2+ was non-inferior to that of hrHPV testing on physician-taken cervical samples (P=0.018). In addition, hrHPV genotyping results were highly concordant between sample types, with almost perfect agreement for HPV16 (k=0.81) and HPV18 (k=0.92). Finally, 91% of participants described brush-based self-sampling as easy-to-use. ConclusionsBrush-based self-sampling in combination with GP5+/6+-PCR EIA hrHPV testing is acceptable to women and valid for assessing the risk of CIN2+ in comparison to hrHPV testing on physician-taken scrapes. In addition, there was high concordance of HPV genotyping results. Therefore, this HPV self-sampling procedure may be considered for use in routine cervical screening.

Comparison of conventional and liquid-based cytology: do the diagnostic benefits outweigh the financial aspect?

We aimed to compare the efficiency of conventional cytology (CC) and new liquid-based cytology (LBC) techniques in the assessment and the accuracy of Pap smears reported as abnormal by histological examinations. Materials and methods: A total of 3488 women who were undergoing routine cervical screening (1308 CC and 2180 LBC) were included in the initial screening. The results were assessed as either satisfactory or unsatisfactory. Satisfactory results were subdivided as negative, atypical squamous cells of undetermined significance (ASCUS), atypical squamous cells for which high-grade lesions could not be excluded (ASC-H), low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous intraepithelial lesion (HGSIL), and cancer. Results: These data show that the rate of unsatisfactory results for the LBC technique (0.05%) was lower than for the CC group (0.5%). Except for ASCUS and cancer cytology, all other atypical cytology results were diagnosed more frequently with CC than with LBC. The rates of detected ASC-H and HGSIL were higher with CC than LBC, and the difference was statistically significant (P < 0.05). Conclusion: LBC has higher satisfaction rates than CC. LBC also detected more true-abnormal cases when compared with CC. The residual specimens from the LBC technique can be used to detect human papillomavirus DNA through immunocytochemistry, if needed. However, the benefits of LBC do not seem to justify the cost. It seems that CC should be the first choice for developing countries with lower incomes.

Evaluation of HPV-16 and HPV-18 Genotyping for the Triage of Women With High-Risk HPV+ Cytology-Negative Results

The ATHENA (Addressing THE Need for Advanced HPV Diagnostics) HPV study evaluated the clinical usefulness of the cobas HPV Test (Roche Molecular Systems, Pleasanton, CA) for high-risk human papillomavirus (HR-HPV) testing (14 HR types) and individual HPV-16/HPV-18 genotyping in women undergoing routine cervical cytology screening in the United States. For the study, 47,208 women were recruited, including 32,260 women 30 years or older with negative cytology. All women with positive results for HR-HPV (n = 4,219) plus a subset of HR-HPV- women (n = 886) were referred for colposcopy and biopsy. The overall prevalence of HR-HPV was 6.7% and of HPV-16/HPV-18 was 1.5%. Cervical intraepithelial neoplasia grade 2 (CIN 2) or worse was found in 1.2% of women examined. The estimated absolute risk of CIN 2 or worse in HPV-16+ and/or HPV-18+ women was 11.4% (95% confidence interval [CI], 8.4%-14.8%) compared with 6.1% (95% CI, 4.9%-7.2%) in HR-HPV+ and 0.8% (95% CI, 0.3%-1.5%) in HR-HPV- women. These analyses validate the 2006 American Society of Colposcopy and Cervical Pathology guidelines for HPV-16/HPV-18 genotyping, which recommend referral to colposcopy of HPV-16/HPV-18+ women with negative cytology.