We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants.
The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing.
The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year.
The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.
We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10(5) person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.
In women aged = 30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30-65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more = CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more = CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without = CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was = 50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30-65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.
Cites: Int J Cancer. 1996 Dec 11;68(6):766-98980181
To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.
13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.
Organised cervical screening programme in Sweden.
12,527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).
Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.
The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).
Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.
Cites: Stat Med. 2012 May 20;31(11-12):1113-2822161769
To assess the performance of a 5-type human papillomavirus (HPV) messenger RNA (mRNA) test in primary screening within the framework of the Norwegian population-based screening programme.
Nationwide register-based cohort study.
In 2003-2004, general practitioners and gynaecologists recruited 18 852 women for participation in a primary screening study with a 5-type HPV mRNA test.
After excluding women with a history of abnormal smears and with cervical intraepithelial neoplasia grade 2 (CIN2+) before or until 3 months after screening, 11 220 women aged 25-69 years were eligible for study participation. The Norwegian Cancer Registry completed follow-up of CIN2+ through 31 December 2009.
Follow-up according to the algorithm for cytology outcomes in the population-based Norwegian Cervical Cancer Screening Programme.
We estimated cumulative incidence of CIN grade 3 or worse (CIN3+) 72 months after the 5-type HPV mRNA test.
3.6% of the women were HPV mRNA-positive at baseline. The overall cumulative rate of CIN3+ was 1.3% (95% CI 1.1% to 1.5%) through 72 months of follow-up, 2.3% for women aged 25-33 years (n=3277) and 0.9% for women aged 34-69 years (n=7943). Cumulative CIN3+ rates by baseline status for HPV mRNA-positive and mRNA-negative women aged 25-33 years were 22.2% (95% CI 14.5% to 29.8%) and 0.9% (95% CI 0.4% to 1.4%), respectively, and 16.6% (95% CI 10.7% to 22.5%) and 0.5% (95% CI 0.4% to 0.7%), respectively, in women aged 34-69 years.
The present cumulative incidence of CIN3+ is similar to rates reported in screening studies via HPV DNA tests. Owing to differences in biological rationale and test characteristics, there is a trade-off between sensitivity and specificity that must be balanced when decisions on HPV tests in primary screening are taken. HPV mRNA testing may be used as primary screening for women aged 25-33 years and 34-69 years.
Cites: Int J Cancer. 2015 Mar 1;136(5):E359-8625220842
Within 2021, Norway intends to complete implementation of HPV DNA-based primary screening for cervical cancer for women 34-69 years, while continue cytology-based screening for women 25-33 years. Over the recent years, the incidence of cervical cancer has increased by 30% among women younger than 40 years. In this subset of women, nearly 30% were diagnosed with a normal smear, as most recent smear, prior the cancer diagnosis. This observation demands quality control of normal smears. The aim of this study was to assess increase in program sensitivity of CIN2+ after follow-up of women with false negative Pap-smears testing positive for a 3-type (-16, -18, -45) HPV mRNA test in a cohort design over one screening interval. 521 women, aged 23-39 years, and no prior history of CIN1+ or HSIL, with an ASC-US or worse smear (ASC-US+) and 1444 women with normal screening cytology comprised the study cohorts. The positivity rate for the 3-type HPV mRNA was 1.9% (28/1444). Rescreening revealed 23 women with ASC-US, two women with LSIL, two women with ASC-H, and one woman with AGUS. If the HPV mRNA-positivity rate and histology findings from samples rescreened were applied to all women with normal cytology, an estimated increase in screening sensitivity of 16.4% (95% CI:15.3-17.5) for CIN2+ and 17.3% (95% CI:16.2-18.4) for CIN3+ were achieved. By rescreening less than 2% of women with normal cytology positive for a 3-type HPV mRNA test, we achieved a significant increase in screening program sensitivity.
We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p
We analysed patterns in the incidence of cervical intraepithelial neoplasia grades 2 and 3 (CIN2, CIN3) and adenocarcinoma in situ (AIS) by age and histology in 1992-2016 in Norway and described changes in screening tests. Incident cases of CIN2, CIN3, AIS and cervical cancer were identified in the Cancer Registry of Norway, as were all women with at least one screening test. The annual percentage change statistic was used to assess point estimates and changes in age-specific and age-standardised incidence rates (IR). Women aged 25-29?years had the highest incidence of cervical precancerous lesions (CIN2: 192.9/10, CIN3: 737.2/10, AIS: 32.5/105 in 2016). The IR of CIN2 increased for all screening ages (25-69?years) from 3.6% to 6.7% per year. CIN3 incidence increased by 1.6% (95% confidence interval [CI] 0.6-2.6) annually. A steep increase in AIS incidence was observed in all age groups (7.1% per year, 95% CI 5.3-8.8). Changes in screening tests and the histological verification of cervical precancerous lesions alone cannot explain the steady increase in incidence we observed over the 25-year study period, and increased exposure to human papillomavirus (HPV) likely plays a role. Age-appropriate treatment of screening-detected cervical precancerous lesions is needed for effective cervical cancer control while avoiding overtreatment and related health risks. In order to perform an appropriate harm-benefit evaluation of cervical cancer control efforts, detailed information on screening technology and background risks, including HPV vaccination status, is needed to create optimal public health policy.