Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: A randomized study.

Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study.

BACKGROUND: Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening. METHODS: A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36,390 women aged 30-49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17,997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18,393, Pap smear arm). RESULTS: Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 229,446 vs. € 782,772). CONCLUSIONS: This study resulted in that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening. TRIAL REGISTRATION: Not registered since this trial is a secondary analysis of an earlier published study (Gustavsson et al., British journal of cancer. 118:896-904, 2018).

Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2.

BACKGROUND: The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables. METHODS: In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software. RESULTS: K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036). CONCLUSIONS: The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.

Invasive cervical tumors with high and low HPV titer represent molecular subgroups with different disease etiology.

Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n = 49) were classified into high- and low-HPV-titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA sequencing, and the results were validated using the AmpliSeq Transcriptome assay. HPV DNA genotyping and RNA sequencing showed that 16.6% of ICC tumors contained very low levels of HPV DNA and HPV transcripts. Tumors with low HPV levels had more mutations with a high allele frequency and fewer mutations with low allele frequency relative to tumors with high HPV titer. A number of genes showed significant expression differences between HPV titer groups, including genes with somatic mutations. Gene ontology and pathway analyses implicated the enrichment of genes involved in DNA replication, cell cycle control and extracellular matrix in tumors with low HPV titer. The results indicate that in low titer tumors, HPVs act as trigger of cancer development whereas somatic mutations are clonally selected and become drivers of the tumor development process. In contrast, in tumors with high HPV titer the expression of HPV oncoproteins plays a major role in tumor development and the many low frequency somatic mutations represent passengers. This putative subdivision of invasive cervical tumors may explain the higher radiosensitivity of ICC tumors with high HPV titer and thereby have consequences for clinical management.

Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.

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 < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.

OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study. RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + . CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.

Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening.

BACKGROUND: The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, - 31, - 35, - 39, - 51, - 56, and - 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening. METHODS: We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples. RESULTS: The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10- 2 and p = 1.89 × 10- 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons. CONCLUSIONS: Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology.

This corrects the article DOI: 10.1038/bjc.2017.85.

Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women.

BACKGROUND: Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities. METHODS: Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-time polymerase chain reaction. RESULTS: HIV-positive women had a significantly higher viral load for combined alpha-9 HPV species compared to HIV-negative women (median 3.9 copies per cell compared to 0.63 copies per cell, P = 0.022). This was not observed for individual HPV types. HIV-positive women with CD4 counts >350/µl had significantly lower viral loads for alpha-7 HPV species (median 0.12 copies per cell) than HIV-positive women with CD4 ≤350/µl (median 1.52 copies per cell, P = 0.008), but low CD4 count was not significantly associated with increased viral load for other HPV species. High viral loads for alpha-6, alpha-7 and alpha-9 HPV species were significant predictors of abnormal cytology in women. CONCLUSION: HIV co-infection significantly increased the combined alpha-9 HPV viral load in women but not viral loads for individual HPV types. High HR-HPV viral load was associated with cervical abnormal cytology.

Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid.

Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence-based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91-1.00) at a specificity of 0.67 (0.40-0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.

Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program.

BACKGROUND: Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear. OBJECTIVE: From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples. DESIGN: A cost-effectiveness analysis. SETTING: The Swedish organized cervical cancer screening program. METHODS: We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. "conventional cytology strategy") and (ii) conventional cytology screening until age 35 years, followed by HR-HPV testing using self-collected vaginal samples in women aged ≥35 years (i.e. "combination strategy"). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies. MAIN OUTCOME MEASURES: Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years. RESULTS: Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from €43,000 to €180,000 per life-years gained without the cost of added life-years, and from €74,000 to €206,000 with costs of added life-years included. CONCLUSION: The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of €80,000 per life-years gained.

Primary high-risk HPV screening for cervical cancer in post-menopausal women.

OBJECTIVE: The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women. METHODS: A cohort of post-menopausal women (n=2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement. RESULTS: High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n=130) and 22% (95% CI 14-32%) (n=17) of these had CIN2+ lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n=12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% CI 38-86%) (n=8), as compared to 14% (95% CI 7-24%) (n=9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population. CONCLUSIONS: Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.

Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types.

BACKGROUND: Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. METHODS: This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. RESULTS: Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. CONCLUSIONS: The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

Voice Therapy Outcome: A Comparison Between Imitation Model Voice Therapy and Verbal Instructions Model Voice Therapy.

OBJECTIVES: The aim was to compare voice outcomes over time in patients treated with Imitation Model voice therapy and Verbal Instructions Model voice therapy. METHODS: A prospective clinical trial was performed with 56 consecutive patients diagnosed with a primary or secondary functional voice disorder. Thirty-one patients were included for voice therapy following the Imitation Model and 25 patients for the Verbal Instructions Model. Assessments included a self-rated Voice Handicap Index, self-perceived hoarseness and vocal fatigue, perceptual voice evaluation by a Speech Language Pathologist, and maximum Voice Range Profiles. All assessments were completed before therapy, at end of therapy, at six-months posttherapy follow-up and 12-months posttherapy follow-up. For maximum Voice Range Profiles group differences were also compared for effects from end-of-treatment to follow-up assessments. Linear mixed models were used for analysis. RESULTS: Comparison between treatment groups showed significantly larger long-term improvement from the baseline, for verbal instructions model as compared to imitation model for Voice Handicap Index total, and also the physical and emotional subscales, while there was no difference between groups for the functional subscale. Also, voice quality improved more after verbal instructions model, as compared to imitation model, at end of therapy. Results from self-rated hoarseness and vocal fatigue showed no difference between groups. There was no difference between treatment groups in the change of maximum Voice Range Profile from end-of-treatment to follow-up assessments. CONCLUSIONS: The study showed that both Imitation Model voice therapy and Verbal Instructions Model voice therapy improved voice function. Compared to Imitation Model, the Verbal Instructions model showed larger long-term effect on physical and emotional aspects of voice function in everyday life. The two approaches for voice therapy might have different impacts on patients' learning.

Incidence of oncogenic HPV and HPV-related dysplasia five years after a negative HPV test by self-sampling in elderly women.

PURPOSE: Cervical cancer prevention for older women can be challenging since there are no specific guidelines for this group. This study aimed to determine the incidence of oncogenic HPV and HPV-related dysplasia in elderly women 5 years after being HPV negative. METHODS: Invited women participated five years earlier in a study where self-sampling for HPV testing was applied, at this time, they were all HPV negative. The women were now, five years later invited to perform self-sampling for HPV testing. Women with a positive result performed a repeat HPV test. Those with a positive repeat HPV test were examined by colposcopy, biopsy and cytology. RESULTS: Of the 804 invited women, 634 (76.9%) agreed to participate in the study and a self-sampling kit was sent to them. Of these, 99.6% (632/634) sent a sample to the HPV laboratory. The participation rate in each age group was 93.3% at age 65, 74.0% at age 70, 80.7% at age 75 and 64.6% at age 80. Overall 18 women (2.8%, 95% CI 3.2 to 6.0) were HPV positive in the first test and 8 (1.3%, 95% CI 0.6 to 2.6) in the second test. Sampling for the second test was done on average 5.4 months after the first test. Fifty per cent (4/8) of the women with a positive repeat test had dysplasia in histology. CONCLUSION: The incidence of HPV in previously HPV-negative elderly women was low. Among women who were HPV positive in a repeat test, there was a high prevalence of low grade dysplasia.

Brush Samples of Oral Lesions to FTA Elute Card for High-risk Human Papilloma Virus Diagnosis.

AIM: To investigate the level of agreement between three non-invasive methods for hrHPV diagnosis in oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC) and in oral mucosal lesions. MATERIALS AND METHODS: For hrHPV DNA FTA Elute card™ and Anyplex II HPV28™ were used and for hrHPV mRNA PreTect SEE™ in tumour patients (n=60), non-tumour lesions (n=51), immunosuppression or previous hrHPV-infection (n=32). RESULTS: The level of agreement between the DNA-methods was 82.2% (k=0.54, p=0.001). Pair-wise comparison for the FTA Elute card were close to the reference (AUC=0.83, 95% CI=0.73-0.90). hrHPV mRNA was diagnosed in 50% of the tumours, with an agreement level of 58.3%, compared to Anyplex II (k=0.17, p=0.04). The hrHPV positivity in oral lesions was 3.9% for immunosuppression and for previous HPV infection 9.4%. CONCLUSION: The FTA card is reliable for hrHPV DNA diagnosis while mRNA gives an insight into viral activity and correlates with severity of the lesion.

Identification of Candidate Protein Biomarkers for CIN2+ Lesions from Self-Sampled, Dried Cervico-Vaginal Fluid Using LC-MS/MS.

Molecular screening programs for cervical cancer detect the presence of human papilloma virus (HPV) in cell material or vaginal fluids. Persistent infection with high-risk HPV is a necessary pre-requisite, but the majority of infections do not lead to pathological states. Additional biomarkers are needed to increase the specificity of the molecular tests. Here, we have investigated the possibility of detecting protein biomarkers using mass spectrometry from dried self-sampled cervico-vaginal fluid deposited on FTA cards. We found significant intra-individual correlations (p < 2.2 × 10-16), although heterogenous protein profiles were obtained between individuals. Out of 3699 proteins found in total, 169 were detected in at least 95% of the samples. Using a discovery/replication design, 18 proteins were found to be significant in the discovery cohort, with higher values in those cases compared to controls. All of these were found to also have higher levels among the cases in the replication cohort, with one protein (DEAD-Box Helicase) remaining statistically significant. Finally, a predictive 7-protein multivariate model was developed with a sensitivity and specificity of 0.90 and 0.55, respectively. Our results demonstrate that robust measurements of protein biomarkers can be obtained from self-sampled dried CVF and that these could be used to predict cervical cancer pre-stages.

Voice Therapy Outcome-A Randomized Clinical Trial Comparing Individual Voice Therapy, Therapy in Group, and Controls Without Therapy.

OBJECTIVE: A stumbling-block in voice therapy is how the patient will be able to apply the new voice technique in everyday life. Possibly this generalization process could be facilitated by giving voice therapy in group because of the natural forum for training voice-to-speech early in communication between the patients in a group setting. The aim of the study was to compare treatment results from individual voice therapy and voice therapy in group, at several time points and in comparison to patients with no voice therapy. METHODS: A randomized treatment study was performed with 77 consecutive patients diagnosed with a functional voice disorder. Thirty-one patients were randomized to individual and group therapy, respectively, and 15 patients to no therapy. The assessments included standardized voice recording and registration of voice range profile (VRP), answering Voice handicap index (VHI) and visual analogue scales for self-hoarseness and self-vocal fatigue, and perceptual voice evaluation by speech-language pathologist. The assessments were performed before, direct after therapy, and three months later in all groups. The 2 therapy groups were also assessed 12 months after therapy. RESULTS: All VHI scores as well as the self-ratings of hoarseness and vocal fatigue, and the perceptual evaluation of voice quality and maximum VRP improved significantly in both therapy groups 3 months after treatment and at 12 months follow-up. There were no significant changes in the control group, with the exception of decreased self-rated hoarseness and increased maximum VRP. Comparisons between treatment groups showed significant larger improvement after group therapy for VHI physical subscale at 12 months, as well as significant lower VHI total score at all measurement sessions and lower subscale scores at 12 months. There were no differences between treatment groups in self-hoarseness or self-vocal fatigue and no difference in perceptual voice quality or VRP. Comparison between controls and treatment groups showed significant larger change in treatment groups from baseline to three months in VHI total and to end of therapy in functional subscale. Treatment groups also showed significant lower scores than controls at each measurement session, for VHI total and physical subscale as well as lower degree of perceptual aberration of voice quality and vocal fatigue, at three months follow-up. CONCLUSIONS: This study shows long-term improvement from behavioral voice therapy, particularly in a group setting. The results indicate the importance of early transfer-to-speech and late posttherapy test to capture whether the goal of voice therapy was fulfilled or not for the patients.

Acceptability of self- collection for human papillomavirus detection in the Eastern Cape, South Africa.

Human papillomavirus (HPV) testing on vaginal self-collected and cervical clinician-collected specimens shows comparable performance. Self-sampling on FTA cards is suitable for women residing in rural settings or not attending regular screening and increases participation rate in the cervical cancer screening programme. We aimed to investigate and compare high-risk (HR)-HPV prevalence in clinician-collected and self-collected genital specimens as well as two different HPV tests on the clinician collected samples. A total of 737 women were recruited from two sites, a community health clinic (n = 413) and a referral clinic (n = 324) in the Eastern Cape Province. Cervical clinician-collected (FTA cards and Digene transport medium) and vaginal self-collected specimens were tested for HR-HPV using the hpVIR assay (FTA cards) and Hybrid Capture-2 (Digene transport medium). There was no significant difference in HR-HPV positivity between clinician-collected and self-collected specimens among women from the community-based clinic (26.4% vs 27.9%, p = 0.601) or the referral clinic (83.6% vs 79.9%, p = 0.222). HPV16, HPV35, and HPV33/52/58 group were the most frequently detected genotypes at both study sites. Self-sampling for HPV testing received a high positive response of acceptance (77.2% in the community-based clinic and 83.0% in referral clinic). The overall agreement between hpVIR assay and HC-2 was 87.7% (k = 0.754). The study found good agreement between clinician-collected and self-collected genital specimens. Self-collection can have a positive impact on a cervical screening program in South Africa by increasing coverage of women in rural areas, in particular those unable to visit the clinics and women attending clinics where cytology-based programs are not functioning effectively.

Temporal trends over 3 decades and intrafamilial clustering of HPV types in Swedish patients with cervical cancer in situ.

Information on HPV type distribution in cervical cancer in situ in different populations is needed for evaluation of prophylactic vaccination programs targeting HPV 16 and 18. In our study, the HPV type prevalence in 1,079 Swedish women from multicase families diagnosed with cervical cancer in situ 1965-1993 was investigated using real-time PCR and archival tissue material. HPV type information was obtained for 974 samples. Among these, HPV 16 (61%) was the dominant type followed by HPV 33/52/58 (24%), HPV 31 (13%) and HPV 18/45 (12%). The detected prevalence of HPV 16 among cancer in situ decreased by 13% over the study period while the group of low frequency high-risk types increased. Related women were not prone to infection by the same type. These data suggest that the prevalence of individual HPV types has changed over time in Swedish patients with cervical cancer in situ. Large-scale studies of pathology biobank materials will enable further insight into the temporal changes of individual HPV types, as baseline information to properly evaluate the effect of vaccine programs. The findings also indicate that genetic susceptibility to cervical cancer operates through general and not type specific susceptibility to HPV infection.