Triaging borderline/mild dyskaryotic Pap cytology with p16/Ki-67 dual-stained cytology testing: cross-sectional and longitudinal outcome study

Background:

Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing.

Methods:

Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results.

Results:

p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6% P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1% P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women.

Conclusions:

Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.     

HPV immunisation and cervical screening—confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study

Background:

To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP).

Methods:

Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status.

Results:

Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained.

Conclusions:

The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.     

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial �C the HPV FOCAL Study

Background:

Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented.

Methods:

The three arms are: Control arm – liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm – hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm – hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years.

Results:

A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+.

Conclusion:

After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.     

Comparing the performance of six human papillomavirus tests in a screening population

Background:

Several new assays have been developed for high-risk HPV testing of cervical samples; we compare six HPV tests in a screening population.

Methods:

Residual material from liquid-based PreservCyt samples was assayed. Four tests (Hybrid Capture 2, Cobas, Abbott and Becton-Dickinson (BD)) measured HPV DNA while two used RNA (APTIMA and NorChip).

Results:

Positivity rates ranged from 13.4 to 16.3% for the DNA-based tests with a significantly lower positivity rate for the Abbott assay. The Gen-Probe APTIMA assay was positive in 10.3% of women, which was significantly lower than all the DNA tests; the NorChip PreTect HPV-Proofer test was much lower at 5.2%. 40 CIN2+ cases were identified, of which 19 were CIN3+. All CIN3+ cases were HPV positive by all tests except for one, which was negative by the Abbott assay and five which were negative by the NorChip test.

Conclusion:

All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.     

A comprehensive evaluation of the accuracy of cervical pre-cancer detection methods in a high-risk area in East Congo

Background:

Given the high burden of cervical cancer in low-income settings, there is a need for a convenient and affordable method for detecting and treating pre-cancerous lesions.

Methods:

Samples for comparing the accuracy of cytology, virology and histology were collected. Identification of HPV E6/E7 mRNA was performed using PreTect HPV-Proofer. HPV DNA detection was performed by GP5+/6+ PCR, followed by reverse line blot (RLB) for typing.

Results:

A total of 343 women, aged 25–60 years, attending gynaecological polyclinics in DR Congo were included for sample enrolment. The test positivity rate was conventional and liquid-based cytology (LBC) at cutoff ASCUS+ of 6.9 and 6.6%, respectively; PreTect HPV-Proofer of 7.3% and consensus DNA PCR for 14 HR types of 18.5%. Sixteen cases of CIN2+ lesions were identified. Of these, conventional cytology identified 66.7% with a specificity of 96.2%, LBC identified 73.3% with a specificity of 96.9%, all at cutoff ASCUS+. HR-HPV DNA detected all CIN2+ cases with a specificity of 85.9%, whereas PreTect HPV-Proofer gave a sensitivity of 81.3% and a specificity of 96.6%.

Conclusion:

Both HPV detection assays showed a higher sensitivity for CIN2+ than did cytological methods. Detecting E6/E7 mRNA from only a subset of HR HPVs, as is the case with PreTect HPV-Proofer, resulted in a similar specificity to cytology and a significantly higher specificity than consensus HR HPV DNA (P<0.0001).     

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy

Background:

The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+).

Methods:

The study enroled 1029 women with abnormal screening cytology (years 2006–2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006–2011).

Results:

During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1–3.1) and 41.8% (95% CI 31.8–53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5–755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation.

Conclusion:

Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.     

Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer

Background:

Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30–65 years, with the primary sample for HPV analysis taken by self-sampling.

Methods:

A total of 8000 women in Uppsala County, aged 30–65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.

Results:

In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18–30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31–51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30–39 years to 24% in women at age 50–65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).

Conclusion:

The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30–65 years.     

HPV self-sampling as an alternative strategy in non-attenders for cervical screening - a randomised controlled trial

Background:

A randomised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self-sample for human papillomavirus (HPV) testing, or to a further invitation to attend for cervical screening.

Methods:

The study was carried out in a Primary Care Trust (PCT) in London between June 2009 and December 2009. In total, 3000 women were randomly selected from persistent non-responders (i.e., who had not responded to at least two invitations to attend for screening). The women were randomised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology. The main outcome measures were (1) percentage of women attending for cervical cytology compared with those returning a self-sample HPV test or attending for cytology subsequent to receiving the kit and (2) percentage of those testing positive for HPV who attended further investigation.

Results:

The total response in the self-sampling group for screening was 10.2%. Of the 1500 women in the control group sent a further invitation for cervical screening, 4.5% attended for cytology screening. This difference is highly statistically significant (P<0.0001). Of the 8 women who tested positive for HPV, 7 attended for a cervical smear and had a concurrent colposcopy. Three of these (43%) had high-grade disease (defined as CIN 2+), with one found to have an invasive cancer (stage 1b) and one CIN 3.

Conclusions:

The value of this intervention relies on the detection of high-grade CIN and early stage cancer with a good prognosis. The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women. Our study suggests that self-sampling could increase participation among non-responders in England, but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country. Other studies are needed to investigate the response to self-sampling in different demographic and geographic settings.     

HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications

Background:

Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening.

Methods:

In all, 25 871 women (29–61) enrolled in our population-based cohort study were offered both cytology and hrHPV testing. High-risk HPV-positive women with normal cytology and an age-matched subcohort of hrHPV-negative women with normal cytology were invited for repeat testing after 1 and/or 2 years and were referred for colposcopy if they presented with abnormal cytology and/or a positive hrHPV test. The hrHPV-positive women with borderline or mild dyskaryosis (BMD) and all women with moderate dyskaryosis or worse (>BMD) were directly referred for colposcopy. Women with BMD and an hrHPV-negative test were advised to repeat cytology at 6 and 18 months and were referred for colposcopy if the repeat cytology test was abnormal. The main outcome measure was CIN grade 3 or worse (CIN3+). Results were adjusted for non-attendance at repeat testing.

Results:

The hrHPV-positive women with abnormal cytology had a CIN3+ risk of 42.2% (95% confidence interval (CI): 36.4–48.2), whereas the hrHPV-positive women with normal cytology had a much lower risk of 5.22% (95% CI: 3.72–7.91). In hrHPV-positive women with normal cytology, an additional cytology step after 1 year reduced the CIN3+ risk to only 1.6% (95% CI: 0.6–4.9) if the repeat test was normal. The CIN3+ risk in women with hrHPV-positive normal cytology was higher among women invited for the first time (29–33 years of age) (9.1% 95% CI: 5.6–14.3) than among older women (3.0% 95% CI: 1.5–5.5).

Conclusion:

Primary hrHPV screening with cytology triage in women aged ⩾30 years is an effective way to stratify women on CIN3+ risk and seems a feasible alternative to cytological screening. Repeat cytology after 1 year for hrHPV-positive women with normal cytology is however necessary before returning women to routine screening.     

Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya

Background:

We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women.

Methods:

Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy.

Results:

In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). CD4 count was negatively associated with prevalence of hrHPV (P<0.001) and CIN2/3 among non-users of cART (P=0.013). Combination antiretroviral therapies users (⩾2 year) had lower hrHPV prevalence (prevalence ratio (PR) vs non-users=0.77, 95% confidence interval (CI): 0.61–0.96) and multiple infections (PR=0.68, 95% CI: 0.53–0.88), but not fewer CIN2/3. The positive predictive value of hrHPV-positivity for CIN2/3 increased from 28.9% at age <35 years to 53.3% in ⩾45 years.

Conclusion:

The burden of hrHPV and CIN2/3 was high and it was related to immunosuppression level. Combination antiretroviral therapies ( ⩾2 year) use had a favourable effect on hrHPV prevalence but cART in our population may have been started too late to prevent CIN2/3.     

Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England

Background:

Knowledge of the prevalence of type-specific human papillomavirus (HPV) infections is necessary to predict the expected, and to monitor the actual, impact of HPV immunisation and to design effective screening strategies for vaccinated populations.

Methods:

Residual specimens of cervical cytology (N=4719), CIN3/CGIN and cervical cancer biopsies (N=1515) were obtained from sites throughout England, anonymised and tested for HPV DNA using the Linear Array typing system (Roche).

Results:

The prevalence of HPV 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous cell carcinomas, 82% in adeno/adenosquamous carcinomas and 63% and 91% in CIN3 and CGIN, respectively. Of all HR HPV-infected women undergoing cytology, non-vaccine HPV types only were found in over 60% of those with mild dyskaryosis or below, and in <20% of those with cancer. In women of all ages undergoing screening, HR HPV prevalence was 16% and HPV 16 and/or 18 prevalence was 5%.

Conclusion:

Pre-immunisation, high-grade cervical disease in England was predominantly associated with HPV 16 and/or 18, which promises a high impact from HPV immunisation in due course. Second-generation vaccines and screening strategies need to consider the best ways to detect and prevent disease due to the remaining HR HPV types.     

Comparison of Hybrid capture 2 testing at different thresholds with cytology as primary cervical screening test

Background:

We evaluated the performance of primary high-risk human papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different thresholds for positivity, in comparison with conventional cytology.

Methods:

We used data of 25 871 women (aged 30–60 years) from the intervention group of the VUSA-Screen study (VU University Medical Center and Saltro laboratory population-based cervical screening study), who were screened by cytology and hrHPV. Primary outcome measure was the number of cervical intraepithelial neoplasia grade 3 or higher (CIN3+), detected within 3 years. We compared baseline cytology testing with three possible hrHPV screening strategies at different relative light unit/cutoff (RLU/CO) thresholds.

Results:

Compared with baseline cytology testing, hrHPV DNA testing as a sole primary screening instrument did not yield a superior sensitivity, as well as lower colposcopy referral rate and lower false positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO threshold with cytology triage at baseline and at 12 months revealed the highest sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a lower colposcopy referral rate than cytology testing (relative colposcopy rate of 0.94). Higher thresholds (>1RLU/CO) yielded lower colposcopy rates, but resulted in substantial loss in sensitivity.

Conclusions:

The hrHPV testing at the commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12 months showed a much higher sensitivity with a lower colposcopy referral rate compared with cytology testing.     

HPV testing as a triage for borderline or mild dyskaryosis on cervical cytology: results from the Sentinel Sites study

Background:

Earlier pilot studies of human papillomavirus (HPV) triage concluded that HPV triage was feasible and cost-effective. The aim of the present study was to study the impact of wider rollout of HPV triage for women with low-grade cytology on colposcopy referral and outcomes.

Methods:

Human papillomavirus testing of liquid-based cytology (LBC) samples showing low-grade abnormalities was used to select women for colposcopy referral at six sites in England. Samples from 10 051 women aged 25–64 years with routine call or recall cytology reported as borderline or mild dyskaryosis were included.

Results:

Human papillomavirus-positive rates were 53.7% in women with borderline cytology and 83.9% in those with mild dyskaryosis. The range between sites was 34.8–73.3% for borderline cytology, and 73.4–91.6% for mild dyskaryosis. In the single site using both LBC technologies there was no difference in rates between the two technologies. The positive predictive value of an HPV test was 16.3% for CIN2 or worse and 6.1% for CIN3 or worse, although there was considerable variation between sites.

Conclusion:

Triaging women with borderline cytological abnormalities and mild dyskaryosis with HPV testing would allow approximately a third of these women to be returned immediately to routine recall, and for a substantial proportion to be referred for colposcopy without repeat cytology. Variation in HPV-positive rates results in differing colposcopy workload.     

Human papillomavirus DNA in men who have sex with men: type-specific prevalence,risk factors and implications for vaccination strategies

Background:

Human papillomavirus (HPV) vaccination of girls will have relatively little effect on HPV-related disease in men who have sex with men (MSM). We determined HPV prevalence and risk factors in MSM to inform the potential effectiveness of vaccinating MSM.

Methods:

Cross-sectional study of 522 MSM aged 18–40 attending a London sexual health clinic who completed a computer-assisted self-interview. Urine and two swabs (anal and penile/scrotal/perianal) were collected and tested using an in-house Luminex-based HPV genotyping system.

Results:

Prevalence of DNA of the vaccine-preventable HPV types in ano-genital specimens of men was 87/511 (17.0%), 166/511 (32.5%) and 232/511 (45.4%) for the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine types, respectively. A total of 25.1% had one of the quadrivalent types, and 7.4% had 2+ types. Median age at first anal sex was 19 (IQR 17–23) and at first clinic attendance was 24 (IQR 20–27). The increase in the odds of any HPV infection per year of age was 4.7% (95% CI 1.2–8.4).

Conclusions:

On the basis of the current infection status, most MSM, even among a high-risk population attending a sexual health clinic, are not currently infected with the vaccine-type HPV. A targeted vaccination strategy for MSM in the UK could have substantial benefits.     

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial

Background:

Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities.

Methods:

We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality.

Results:

Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4–1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4–2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6–1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9–1.4). Diindolylmethane supplementation was well tolerated.

Conclusion:

The results suggest that short-term DIM supplementation (150 mg day⁻¹) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.     

Self-sampling of the vaginal fluid at home combined with high-risk HPV testing

Background:

Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation.

Methods:

A total of 2829 women 30–58 years old, who had not attended the organised screening for ⩾6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method).

Results:

A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30–39 years old to 2.9% in women ⩾50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2–3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2–3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)–CIN 3)) were included.

Conclusion:

The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2–3) in comparison those with a single cytological smear.     

Human papillomavirus infection in women with and without cervical cancer in Karachi, Pakistan

Background:

No data exist on the population prevalence of, or risk factors for, human papillomavirus (HPV) infection in predominantly Muslim countries in Asia.

Methods:

Cervical specimens were obtained from 899 married women aged 15–59 years from the general population of Karachi, Pakistan and from 91 locally diagnosed invasive cervical cancers (ICCs). HPV was detected using a GP5+/6+ PCR-based assay.

Results:

The prevalence of HPV in the general population was 2.8%, with no evidence of higher HPV prevalence in young women. The positivity of HPV was associated with women''s lifetime number of sexual partners, but particularly with the age difference between spouses and other husbands'' characteristics, such as extramarital sexual relationships and regular absence from home. The HPV16/18 accounted for 24 and 88% of HPV-positive women in the general population and ICC, respectively.

Conclusion:

Cervical cancer prevention policies should take into account the low HPV prevalence and low acceptability of gynaecological examination in this population.     

End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age

Background:

Previous analyses from a randomised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years.

Methods:

We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations.

Results:

Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported.

Conclusions:

The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24–45 years, regardless of previous exposure to HPV vaccine type.     

Distribution of HPV types associated with cervical cancers in Scotland and implications for the impact of HPV vaccines

Background/metho:

This study evaluated human papillomavirus (HPV) type prevalence in 370 Scottish invasive cervical cancers (ICCs) using HPV genotyping and HPV mRNA detection.

Results:

HPV 16 and/or 18 was detected in 72% of cancers overall and in 82% of HPV-positive cancers. HPV 45 and 16 were the most frequently transcribed types.

Conclusion:

A significant reduction in ICC in Scotland should be achieved through the HPV immunisation programme.