Papillomavirus Research最新文献

The prognostic impact of human papillomavirus (HPV) type on invasive cervical cancer (ICC) was analyzed for 137 women treated for ICC at a single institution between 1999 and 2007. The study subjects were divided into three groups according to HPV genotype: HPV16-positive (n = 59), HPV18-positive (n = 33), and HPV16/18-negative ICC (non-HPV16/18, n = 45). The median follow-up time was 102.5 months (range, 5–179). The 10-year overall survival (10y-OS) rates in women with FIGO stage I/II disease were similar among HPV genotypes: 94.7% for HPV16 (n = 39), 95.2% for HPV18 (n = 26), and 96.4% for non-HPV16/18 (n = 29). However, the 10y-OS rates in women with FIGO stage III/IV tumors were 73.7% for HPV16 (n = 20), 45.7% for HPV18 (n = 7), and 35.7% for other types (n = 16), with significantly higher survival in HPV16-positive compared with HPV16-negative ICC (10y-OS; 73.7% vs. 39.5%, P = 0.04). This difference in FIGO stage III/IV tumors remained significant after adjusting for age and histology (hazard ratio 0.30, 95% confidence interval 0.09–0.86, P = 0.02). These results suggest that detection of HPV16 DNA may be associated with a favorable prognosis in patients with FIGO stage III/IV ICC. Given that most women with FIGO stage III/IV tumors received concurrent chemoradiotherapy, this finding may imply that HPV16-positive tumors are more chemoradiosensitive.

High risk HPV infection is the necessary cause for the development of precancerous and cancerous lesions of the cervix. Among HPV, HPV16 represents the most carcinogenic type. Since the determination of HPV16 DNA load could be clinically useful, we assessed quantitative real-time PCR targeting E6HPV16 and albumin genes on two different platforms. Series of SiHa cells diluted in PreservCyt were used to assess repeatability and reproducibility of two in-house real-time PCR techniques run in two different laboratories to determine HPV16 load. Furthermore, 97 HPV16 positive cervical samples were evaluated to estimate inter-center variability using Bland-Alman plots. As a whole, both techniques presented coefficients of variation for HPV16 load measurement similar to those established for other virus quantification with commercial kits. Moreover, the two real-time PCR techniques showed a very good agreement for HPV16 load calculation. Finally, we emphasize that robust HPV16 DNA quantification requires normalization of viral load by the cell number.

Objectives

People living with HIV have increased Human Papillomavirus (HPV) related lesions and malignancies. We describe HPV DNA recovered from the cervix and anal canal, explore the effect of vaccination on HPV detection, and examine the durability of vaccine titers in women living with HIV-1 who were vaccinated with the quadrivalent HPV vaccine.

Methods

AIDS Clinical Trials Group A5240 was a prospective study of the quadrivalent HPV (qHPV) vaccine in 315 HIV-1 infected women in three CD4 strata (A: >350, B; 201–350, C: ≤200 cells/mm³). Vaccine was administered at entry, week 8 and week 24. Cervical and anal HPV DNA specimens were collected at baseline, weeks 28 and 52; serum for antibody testing was obtained at baseline, weeks 28 and 72.

Results

Vaccine antibody titers decreased across all four HPV types at week 72 compared to week 28. Lower proportions of sustained seropositivity were observed in women with lower CD4 counts for all four vaccine types, with the lowest titers for HPV 18. Despite the decrease, the geometric mean titer levels were above the seroconversion cut-off levels for all types except HPV 18 in the lowest CD4 stratum. Of the 174 participants who had a negative baseline HPV 16 antibody and developed antibody response at week 28, 95%, 88%, and 86% retained seropositivity at week 72 in strata A, B, and C respectively. Lower antibody retention was observed in women with CD4 < 200 compared to CD4 > 350 (p = 0.016). Anal HPV detection was more prevalent compared to cervical detection at all visits. Among high risk types, type 52, 31, 16, 18 and 51 were the most common in the cervical compartment, while types 16, 35, 18, and 51 were the most prevalent in the anal canal at baseline (listed in the order of prevalence). Later detection of HPV not present at baseline was uncommon in either compartment. Serial recovery of HPV over time was more commonly observed in the anal canal.

Conclusion

The qHPV vaccine elicits durable titer response above the seroconversion cut-off levels in HIV-infected women. However, the titer levels were substantially lower by Week 72, most noticeably in type 18. HPV DNA was detected more frequently in the anal canal. Detection of non-vaccine high risk HPV suggests a role for the nonavalent vaccine.

Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype.

The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation.

In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors.

The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma

Commercial assays measuring HPV E6 viral oncoproteins, E6/E7 mRNA or DNA were used to test neck lymph node fine needle aspirates (FNA) and oropharyngeal samples (saliva and oral swabs) from 59 Canadian patients with oropharyngeal squamous cell carcinomas (OPSCC). Overall agreements of p16 antigen staining of tumors to FNA tested for OncoE6™, Aptima HPV E6/E7 mRNA and cobas HPV DNA were 81.4% (k 0.53), 94.9% (k 0.83) and 91.1% (k 0.73) respectively. Using HPV presence in a subset of 25 tumors as the comparator, overall agreement was 64.0% (k 0.08) with OncoE6™, 88.0% (k 0.65) with Aptima HPV E6/E7 mRNA and 91.7% (k 0.70) with cobas HPV DNA. HPV testing of oropharyngeal samples yielded lower agreements with tumor markers; 23.7–24.0% (k 0.02), 55.9–68.0% (k 0.24–0.37) and 78.9–86.9% (k 0.49–0.58) in the 3 respective tests. HPV 16 was present in 93.7–100% of the samples tested and showed 100% genotype agreement between FNA and tumors. The high rates for HPV E6 oncoproteins and E6/E7 mRNA suggests most patients were experiencing transcriptionally active HPV-related OPSCC. Results from these commercial assays performed on FNA but not oropharyngeal samples showed moderate to very good agreements with p16 and HPV testing of tumors.

Objective

This study was conducted to determine the prevalence and distribution of high-risk human papillomavirus (HR-HPV) genotypes among sexually active women in Tenkodogo, Burkina Faso.

Methods

Among 131 sexually active women attending the Tenkodogo Urban Medical Center, endocervical samples were collected prior to screening for precancerous lesions. After viral DNA extraction, fourteen HR-HPV genotypes were characterized by real-time multiplex PCR in these cervical samples.

Results

The mean age was 35.5 ± 9.5 years. Of the 131 women, 45 were infected with at least one HR-HPV genotype. The prevalence of HR-HPV infection among these women was 34.4%. Among the 45 oncogenic HPV-infected women, single HR-HPV genotype was found in 55.6% while 44.4% were infected with more than one HR-HPV genotype. The most frequent genotypes were HPV56 (36.5%), HPV66 (36.5%).

Conclusion

Tenkodogo women included in this study had a higher prevalence of HPV 56, HPV 66. A larger study with a more representative sample would therefore be needed to determine predominant oncogenic genotypes in the subregion and especially in cancer cases.

Frequent Pap testing is recommended among women living with HIV (WLWH) due to their elevated risk for cervical cancer. However, there are few recent longitudinal evaluations of utilization and determinants of Pap testing among WLWH. Medical and pathology records of WLWH seen at Johns Hopkins Hospital between 2005 and 2014 were assessed using Prentice, Williams, Peterson models.

Of 554 WLWH in care for ≥ 18 months, 79% received Pap testing, however only 11% consistently received Pap testing at the recommended interval. Some women (5%) were consistently under-screened (tested at longer intervals) and 21% did not receive any Pap testing at during follow-up.

WLWH with decreased likelihood of screening included older women, injection drug users, whites and those who had lived for longer with HIV. In contrast, only women with a prior abnormal Pap result were more likely to receive Pap testing. CD4 cell count and health insurance were not significant determinants.

Although many WLWH in care received Pap testing, some WLWH were unscreened or underscreened. Determinants of Pap testing for WLWH include socio-demographic factors and a prior abnormal result; these present potential targets in an urban HIV care setting for closer monitoring and directed interventions to improve utilization among WLWH.

In 2008, a quadrivalent human papillomavirus (HPV) vaccine (genotypes 6, 11, 16, 18) became available in New Zealand. This study investigated whether the proportion of cervical intraepithelial neoplasia grade 2 (CIN2) lesions associated with HPV genotypes 16 and 18 changed over time in young women recruited to a prospective CIN2 observational management trial (PRINCess) between 2013 and 2016. Partial HPV genotyping (16, 18, or other high risk HPV) was undertaken on n = 392 women under 25 years (mean age 21.8, range 17–24) with biopsy-diagnosed CIN2. High risk HPV genotypes were detected in 96% of women with CIN2 lesions. Between 2013 and 2016, the proportion of women whose liquid-based cytology samples were HPV 16 or 18 positive decreased from 43% to 13%. HPV vaccination status was known for 78% of women. Between 2013 and 2016, the proportion of HPV 16/18 positivity did not significantly change in HPV-vaccinated women, but decreased from 66% to 17% in unvaccinated women. The reducing proportion of HPV 16/18-related CIN2 in our cohort of young New Zealand women may be attributable to the introduction of a national HPV vaccination program. The substantial decrease in HPV 16/18 positivity observed in unvaccinated women is likely to be due to a herd effect.

The performance of different clinical screening algorithms comprising point-of-care HPV-DNA testing using self-collected vaginal (‘V’) specimens, and visual inspection of the cervix with acetic acid (VIA) was evaluated in Papua New Guinea.

Women aged 30–59 years provided V specimens that were tested at point-of-care using the Xpert HPV Test (Cepheid, Sunnyvale, CA). A clinician-collected cervical (‘C’) specimen was then collected for point-of-care Xpert testing, and liquid-based cytology (LBC). Following this, VIA examination was conducted, blind to HPV test results, and ablative cervical cryotherapy provided if indicated. Detection of high-grade squamous intraepithelial lesion (HSIL) by LBC was the reference standard used to evaluate clinical screening algorithms.

Of 1005 women, 36 had HSIL+. Xpert HPV Test performance using V specimens (sensitivity 91.7%, specificity 87.0%, PPV 34.0%, NPV 99.3%) was superior to VIA examination alone (51.5%, 81.4%, 17.5%, 95.6% respectively) in predicting underlying HSIL+. A screening algorithm comprising V specimen HPV testing followed by VIA examination had low sensitivity (45.5%) but comparable specificity, PPV and NPV to HPV testing alone (96.3%, 45.5%, 96.3% respectively).

A ‘test-and-treat’ screening algorithm based on point-of-care HPV testing of V specimens had superior performance compared with either VIA examination alone, or a combined screening algorithm comprising HPV testing plus VIA.

Japan has no national vaccine registry and approximately 1700 municipalities manage the immunization records independently. In June 2013, proactive recommendations for the human papillomavirus (HPV) vaccine were suspended after unconfirmed reports of adverse events following immunization in the media, despite no vaccine safety signal having been raised. Furthermore, studies assessing HPV vaccine safety and effectiveness published post suspension are predominantly based on self-reported information. Our aim was to examine the accuracy of self-reported vaccination status compared with official municipal records. Participants were women aged 20–22 yrs, who were attending for cervical screening in Niigata city. Among the 1230 eligible registrants, vaccine uptake, defined as any dose, was 75.0% and 77.2% according to a self-reported questionnaire and municipal records, respectively. The accuracy rate of self-reported information was as follows: positive predictive value (PPV) was 87.7%; negative predictive value (NPV) was 54.5%; sensitivity was 85.2%; and specificity was 59.8%. The validity of self-reported information was only moderate (Kappa statistic = 0.44, 95% confidence interval 0.37–0.50). This combined with the low NPV may lead to reduced estimation of effectiveness and safety. A more reliable method, such as a national HPV vaccine registry, needs to be established for assessing HPV immunization status in Japan.