Vaginal self-sampling is a cost-effective way to increase participation in a cervical cancer screening programme: a randomised trial

Background:

Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus (HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening.

Methods:

In March 2012, 6000 unscreened women aged 30–65 years, living in a French region covered by a screening programme, who had not responded to an initial invitation to have a Pap smear were equally randomised to three groups: ‘no intervention'' ‘recall'', women received a letter to have a Pap smear; and ‘self-sampling'', women received a self-sampling kit to return to a centralised virology laboratory for PCR-based HPV testing.

Results:

Participation was higher in the ‘self-sampling'' than in the ‘no intervention'' group (22.5% vs 9.9%, P<0.0001; OR 2.64) and ‘recall'' group (11.7%, P<0.0001; OR 2.20). In the ‘self-sampling'' group, 320 used the self-sampling kit; for 44 of these women with positive HR-HPV test results, 40 had the recommended triage Pap smear. The ICER per extra screened woman was 77.8€ and 63.2€ for the ‘recall'' and ‘self-sampling'' groups, respectively, relative to the ‘no intervention'' group.

Conclusions:

Offering an in-home, return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening.     

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.     

Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: a randomised study

Background:

Most women with cervical cancer have not participated in Pap-smear screening. Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate.

Methods:

A total of 4060 women, 39–60 years old, who had not attended the organised Pap-smear screening for 6 years or more were randomised into two equal groups. A study group was offered to self-sample vaginal fluid (Qvintip) at home and/or recommended to attend the Pap-smear screening. The collected fluid after self-sampling was examined for the presence of high-risk HPV (Hybrid Capture 2 method). Controls were only recommended to attend the Pap-smear screening. The end point was a histological identification of CIN2–3.

Results:

The participation rate was 39% (771 out of 2000) in the self-sampling group and 9% (188 out of 2060) in the conventional cytology (P<0.001). The number of histological CIN2–3 alterations detected was 0.4% (8 out of 2000) among women offered self-sampling of vaginal fluid and 0.07% (3 out of 4060) in women offered Pap-smears. The odds ratio (OR) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2–3 was OR=5.42 (95% CI: 1.30–31.8).

Conclusion:

Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2–3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening.     

The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600)

Background:

In Italy, cervical cancer screening programmes actively invite women aged 25–64 years. Programmes are hindered by low participation.

Methods:

A sample of non-responder women aged 35–64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home.

Results:

Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82–1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45–0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10–1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24–2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61–1.50), a prevalently rural area.

Conclusions:

Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.     

Sexual healthcare professionals' views on HPV vaccination for men in the UK

Background:

Human Papillomavirus (HPV) vaccination for men could prevent anal cancers amongst men who have sex with men (MSM).

Methods:

An e-survey of attitudes towards vaccination for men in the UK was conducted in July–August 2014.

Results:

Among 325 sexual health professionals, 14% were already vaccinating men against HPV, 83% recommended gender-neutral HPV vaccination and 65% recommended targeting MSM. Over 50% reported having poor knowledge about the use of HPV vaccine for MSM and the skills to identify MSM likely to benefit from HPV vaccination.

Conclusions:

Clear advice and guidelines on HPV vaccine use for men at sexual health clinics are required to ensure equitable opportunities for vaccination.     

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.     

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.     

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.     

Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in prevalence of HPV 16/18 and closely related HPV types

Background:

In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12–13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12–13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%.

Methods:

To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV.

Results:

From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated.

Conclusions:

This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake.     

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

Background:

Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening.

Methods:

33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated.

Results:

Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them.

Conclusion:

The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.     

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.     

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye

Background:

Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period.

Methods:

Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC).

Results:

Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997–2004) to 30% (2005–2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10–0.47). Only one OSCC was HPV+.

Conclusions:

In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.     

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.     

Associations between human papillomavirus and history of cancer among U.S. adults in the National Health and Nutrition Examination Survey (2003–2010)

Background:

Human papillomavirus (HPV) is an infectious agent that has been associated with human cancer. We have updated the U.S. population sero-prevalence using a large National Health and Nutrition Examination Survey (NHANES) sample of adults from 2003 to 2010, and have analysed the associations between HPV seropositivity and self-reported history of cancer.

Methods:

Four cross-sectional cycles (2003–2004, 2005–2006, 2007–2008, and 2009–2010) were used, for a total of 12 759 participants who had both cancer history and HPV serum information.

Results:

The sero-prevalences of HPV types 6, 11, 16, and 18 were 15.0%, 4.8%, 11.5%, and 4.1%, respectively. Females had significantly higher HPV prevalence than males (P<0.05) for all subtypes. Positive associations between HPV 16/18 seropositivity and lifetime history of any cancer (adjusted odds ratio-OR_adj=1.68; 95% CI: 1.35, 2.01), history of any of eight selected cancers (OR_adj=2.63; 95% CI: 1.78, 3.90), lung cancer (OR_adj=5.14; 95% CI: 1.29, 20.44), and cervical cancer (OR_adj=2.55; 95% CI: 1.63, 3.98) were observed.

Conclusions:

The finding of significant associations between HPV 16/18 seropositivity and lifetime history of cancer adds epidemiological evidence to the carcinogenicity potential of HPV 16 and 18 in other tissues. With increasing coverage of the HPV vaccine in the U.S., future NHANES data and sample collection may allow further detailed evaluation of the population impact of the HPV vaccination on cancer prevention.     

Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer

Background:

Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.

Methods:

We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.

Results:

Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL_high=96%, HPV-positive/TIL_low=59%). Survival of HPV-positive/TIL_low patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a ‘training'' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67% false-positive rate 5.6% AUROC=0·82).

Interpretation:

Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.     

Human papillomavirus infection in Beijing, People's Republic of China: a population-based study

Background:

No recent data exist on human papillomavirus (HPV) infection in Beijing, People''s Republic of China.

Materials and method

We interviewed and examined a representative, randomly selected sample of 5552 sexually active women aged 25–54 years. Cervical cell samples were analysed for HPV DNA by a MY09/11-based PCR assay.

Results:

Human papillomavirus prevalence was 6.7% overall and 4.8% among women without cervical abnormalities. Of the 21 subtypes identified, HPV16 was the commonest type (2.6% overall; 39.1% of HPV-positive women), followed by HPV 58 (1.0%), 33 (0.8%), 43 (0.7%) and 56 (0.7%). High-risk HPV types predominated in all age groups. Human papillomavirus prevalence was highest in young to middle-aged women. Marital status, number of husband''s sexual partners, age at sexual debut and nulligravidity were all associated with being HPV positive.

Conclusions:

In our survey, HPV 16, HPV 58 and HPV 33 were the most prevalent HPV types in Beijing, indicating the potential for the prophylactic HPV 16/18 vaccine in China.     

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.     

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

Background:

In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.

Methods:

We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012.

Results:

By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women.

Conclusions:

To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.     

Cost and logistics of alternative roll-out options for implementing human papillomavirus testing as a triage in cervical screening: results of the sentinel sites study

Background:

Previous studies have indicated that human papillomavirus (HPV) testing as a triage for managing equivocal cytology is cost-effective. The aim of this study was to assess the costs of alternative roll-out options.

Methods:

Detailed cost estimates were collected from six laboratories where HPV triage had been implemented. Costs were assessed for the two different service delivery models that were implemented; a ‘hub and spoke model'' of central HPV testing in a microbiology laboratory with separate cytology laboratories, and an ‘integrated model'' where HPV testing was conducted within the cytology laboratory.

Results:

Comparison of alternative delivery models indicated that setting up HPV processing within existing cytology laboratory, i.e., an ‘integrated cytology/HPV laboratory'' generated savings in staff time amounting to between £2.54 and 4.86 per sample processed. Running full HPV testing batches was also an important consideration. For full batches to be run on a twice weekly basis requires having no more than two laboratories per Strategic Health Authority.

Conclusions:

To be cost-efficient, and to meet turn-around times, HPV testing needs to be conducted at integrated cytology/HPV testing centres with sufficient throughput to run full batches of HPV tests.