Genotyping of human papillomavirus in triaging of low-grade cervical cytology.

OBJECTIVE: The objective of the study was to evaluate whether typing of human papillomavirus (HPV) among women with low-grade cervical cytology can improve the ability to identify women with cervical cancer or cervical intraepithelial neoplasia grade III (CIN III or worse). STUDY DESIGN: A total of 1595 women with low-grade cervical cytology participating in a randomized implementation trial of HPV triaging using Hybrid Capture II were also HPV genotyped and CIN III or worse predictive values evaluated. RESULTS: HPV 16 was detected in 57% of cases with CIN III or worse but only among 24% of all tested women. Testing for the 3 HPV types with highest risk (HPV16/31/33) detected 77% of CIN III or worse, with 36% of women testing positive. Positivity for the other high-risk HPV types had a decreased risk for CIN III or worse. CONCLUSION: Different high-risk HPV types confer different risks for the presence of CIN III or worse, implying that HPV genotyping could be useful for the optimization of triaging strategies

Vaccination With Moderate Coverage Eradicates Oncogenic Human Papillomaviruses If a Gender-Neutral Strategy Is Applied

jiaa099Human papillomavirus (HPV) vaccination of girls with very high (\gt;90\ coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy.We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms. In 2007–2010, 11 662 of 20 513 of 40 852 of 39 420 resident boys/girls from 1992 to 1995 birth cohorts consented. In 2010–2014, cervicovaginal samples from vaccinated and unvaccinated girls at age 18.5 years were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Vaccine efficacy for vaccinated girls, HE for unvaccinated girls, and the protective effectiveness (PE) for all girls were estimated. We extended the community-randomized trial results about vaccination strategy with mathematical modeling to assess HPV eradication.The HE and PE estimates in the 1995 birth cohort for HPV18/31/33 were significant in the gender-neutral arm and 150\% and 40\% stronger than in the girls-only arm. Concordantly, HPV18/31/33 eradication was already predicted in adolescents/young adults in 20 years with 75\% coverage of gender-neutral vaccination. With the 75\% coverage, eventual HPV16 eradication was also predicted, but only with the gender-neutral strategy.Gender-neutral vaccination is superior for eradication of oncogenic HPVs.Peer reviewe

Population-level effects of human papillomavirus vaccination programs on infections with nonvaccine genotypes

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important

High-Throughput Monitoring of Human Papillomavirus Type Distribution

Background: There is a need for a rapid and cost-effective evaluation of the effects of different human papillomavirus (HPV) vaccination strategies. Sexually active adolescents are a preferred target group for monitoring, as effects on HPV prevalence would be measurable shortly after implementation of vaccination programs. Methods: The Swedish Chlamydia trachomatis testing program offers free Chlamydia trachomatis testing and reaches a majority of all adolescents in the population. We anonymized the 44,146 samples submitted for Chlamydia trachomatis testing in Southern Sweden during March to November 2008 and conducted HPV genotyping using PCR followed by mass spectrometry. Results: The HPV positivity peaked at 54.4% [95% confidence interval (CI), 52.2-56.6] among 21-year-old women and at 15.0% (95% CI, 12.4-17.6) among 23-year-old men. The HPV positivity was 37.8% (95% CI, 37.3-38.3) for women and 11.2% (95% CI, 10.6-11.8) for men. The most prevalent types among women were HPV 16 (10.0%; 95% CI, 9.7-10.3) and HPV 51 (6.0%; 95% CI, 5.7-6.3) and, among men, HPV 16 (2.1%; 95% CI, 1.8-2.4) and HPV 6 and HPV 51 (1.7%; 95% CI, 1.5-1.9). Conclusion: The high HPV prevalences seen in the Chlamydia trachomatis screening population enables monitoring of the HPV type distribution among sexually active adolescents at high precision. Impact: Effectiveness of HPV vaccination programs in terms of reducing HPV infections has been difficult to measure because of logistic constraints. We describe a system for high-throughput monitoring of HPV type-specific prevalences using samples from the Chlamydia trachomatis screening program. Cancer Epidemiol Biomarkers Prev; 22(2); 242-50. (c) 2012 AACR

Evaluation of human papillomavirus DNA detection in samples obtained for routine Chlamydia trachomatis screening.

The costs and logistics involved in obtaining samples is a bottleneck in large-scale studies of the circulation of human papillomavirus (HPV), which are useful for monitoring and optimisation of HPV-vaccination programs. Residual samples obtained after screening for Chlamydia trachomatis could constitute a convenient, low-cost solution

Modified General Primer PCR System for Sensitive Detection of Multiple Types of Oncogenic Human Papillomavirus▿

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer and cervical dysplasia. Accurate and sensitive genotyping of multiple oncogenic HPVs is essential for a multitude of both clinical and research uses. We developed a modified general primer (MGP) PCR system with five forward and five reverse consensus primers. The MGP system was compared to the classical HPV general primer system GP5+/6+ using a proficiency panel with HPV plasmid dilutions as well as cervical samples from 592 women with low-grade cytological abnormalities. The reference method (GP5+/6+) had the desirable high sensitivity (five copies/PCR) for five oncogenic HPV types (HPV type 16 [HPV-16], HPV-18, HPV-56, HPV-59, and HPV-66). The MGP system was able to detect all 14 oncogenic HPV types at five copies/PCR. In the clinical samples, the MGP system detected a significantly higher proportion of women with more than two concomitant HPV infections than did the GP5+/6+ system (102/592 women compared to 42/592 women). MGP detected a significantly greater number of infections with HPV-16, -18, -31, -33, -35, -39, -42, -43, -45, -51, -52, -56, -58, and -70 than did GP5+/6+. In summary, the MGP system primers allow a more sensitive amplification of most of the HPV types that are established as oncogenic and had an improved ability to detect multiple concomitant HPV infections

Human papillomavirus type-specific persistence and recurrence after treatment for cervical dysplasia.

Human papillomavirus (HPV) infection is a necessary factor in the cervical cancer development. Also after treatment for cervical dysplasia, HPV can be present and promote the recurrence of cervical disease. In the present study, the aim was to perform a long-term follow-up on the ability of HPV testing with genotyping, as compared with cytology, to predict recurrence of high-grade cervical intraepithelial neoplasia and to evaluate the effectiveness of treatment with loop electrosurgical excision procedure (LEEP) conization. Cervical samples for HPV DNA testing and cytological analysis were obtained from 178 women with abnormal smears referred for treatment with LEEP conization. These women were scheduled for HPV DNA testing and Pap smears before and 3, 6, 12, 24, and 36 months after treatment. Three years after treatment 3.1% (N = 4) of women were still persistently HPV-positive with the same type as had been detected at treatment. Recurrent or residual cervical intraepithelial neoplasia II+ in histopathology was found among 9 (5.1%) women during follow-up. All of these women had type-specific HPV-persistence (sensitivity 100% [95% CI 63-100%] and specificity 94.7% [89.8-97.4%]), but only 7/9 had abnormal cytology (sensitivity 77.8% [40.2-96.1%] and specificity 94.7% [89.8-97.4%]). No recurrent or residual disease was found among women with any other patterns of HPV positivity (e.g., type change or fluctuating positivity) (sensitivity 0% [95% CI 0-37.1%] and specificity 80.5% [73.5-86.0%]). In conclusion, only type-specific HPV persistence predicted recurrent or residual disease, and HPV genotyping appears useful to improve the specificity when using HPV testing in post-treatment follow-up. J. Med. Virol. © 2013 Wiley Periodicals, Inc

HPV73 in cervical cancer and distribution of HPV73 variants in cervical dysplasia

HPV73 is classified as possibly oncogenic and is not recognized by most commercial primary HPV screening platforms. The aim was to determine the prevalence of HPV73 among invasive cervical cancers, formalin-fixed paraffin embedded (FFPE) samples (N = 69), from southern Sweden during 2009 to 2010. Another aim was to determine proportions of HPV73 among Aptima HPV assay negative cervical cancers (N = 9, out of 206 cancers) and of high-grade cytological cervical diagnosis (N = 75, out of 5807 high grade lesions) in liquid-based cytology (LBC) samples collected between 2016 and 2019. We also investigated the distribution of HPV73 variants A1, A2 and B among HPV73-positive cases. HPV73 was detected by multiplex MGP-PCR and Luminex, and HPV73 variants were identified by sequencing PCR amplicons. HPV73 was detected in 2.9% (2/69, 95% CI: 0.18-9.9) of the FFPE cervical cancer series. Among the Aptima HPV-negative LBC samples, HPV73 was present in 55.5% (5/9) of the cancers and 29.3% (22/75) of the different grades of cervical diagnosis. The A1, A2 and B variants were present in 6.9% (2/29), 82.7% (24/29) and 10.3% (3/29) of the HPV73-positive women, respectively. Among the seven HPV73 cancer cases (two FFPE samples and five LBC samples), six A2 and one A1 isolate were detected. In summary, the A2 variant of HPV73 was most common in our region. In addition, the observed prevalence of HPV73 (2.9%) in cervical cancers and its relative high occurrence (55.5%) among Aptima HPV-negative cancers urge that detection of HPV73 should be included in future primary HPV screening programs

HPV73

HPV73 is classified as possibly oncogenic and is not recognized by most commercial primary HPV screening platforms. The aim was to determine the prevalence of HPV73 among invasive cervical cancers, formalin-fixed paraffin embedded (FFPE) samples (N = 69), from southern Sweden during 2009 to 2010. Another aim was to determine proportions of HPV73 among Aptima HPV assay negative cervical cancers (N = 9, out of 206 cancers) and of high-grade cytological cervical diagnosis (N = 75, out of 5807 high grade lesions) in liquid-based cytology (LBC) samples collected between 2016 and 2019. We also investigated the distribution of HPV73 variants A1, A2 and B among HPV73-positive cases. HPV73 was detected by multiplex MGP-PCR and Luminex, and HPV73 variants were identified by sequencing PCR amplicons. HPV73 was detected in 2.9% (2/69, 95% CI: 0.18-9.9) of the FFPE cervical cancer series. Among the Aptima HPV-negative LBC samples, HPV73 was present in 55.5% (5/9) of the cancers and 29.3% (22/75) of the different grades of cervical diagnosis. The A1, A2 and B variants were present in 6.9% (2/29), 82.7% (24/29) and 10.3% (3/29) of the HPV73-positive women, respectively. Among the seven HPV73 cancer cases (two FFPE samples and five LBC samples), six A2 and one A1 isolate were detected. In summary, the A2 variant of HPV73 was most common in our region. In addition, the observed prevalence of HPV73 (2.9%) in cervical cancers and its relative high occurrence (55.5%) among Aptima HPV-negative cancers urge that detection of HPV73 should be included in future primary HPV screening programs