Burden of anal squamous cell carcinoma, squamous intraepithelial lesions and HPV16 infection in solid organ transplant recipients: A systematic review and meta-analysis

The number of solid organ transplant recipients (SOTR), and their life expectancy, is increasing, with higher risk for long-term complications from immunosuppression. We carried out a systematic review describing the burden of anal squamous cell carcinoma (SCC), and its surrogates, in SOTR. We conducted mixed effect model-based meta-analyses evaluating incidence of anal SCC [standardised incidence ratio (SIR) versus general population, and absolute incidence rate (IR)], prevalence of anal squamous abnormalities and human papillomavirus (HPV) 16. Generalised I2 statistics were calculated, quantifying heterogeneity. Anal SCC incidence in SOTR was elevated versus the general population (pooled SIR = 6.8, 95% CI 4.3-10.9; six studies including 241,106 SOTR; I2 =82.3%), with an absolute IR of 12.3 (95% CI 10.4-14.7) per 100,000 person-years (five studies including 1,079,489 person-years; I2 =0%). Prevalence of abnormal anal cytology was 12.9% (95% CI 9.2-17.7%; six studies including 328 SOTR; I2 =17.4%). For histology, the pooled prevalence estimate of anal squamous intraepithelial lesions was 22.4% (95% CI 17.3-28.5%; three studies including 214 SOTR; I2 =0%), with 4.7% (95% CI 2.5-8.5%; I2 =0%) high-grade squamous intraepithelial lesions. Pooled anal HPV16 prevalence was 3.6% (95% CI 1.6-7.8%; four studies including 254 SOTR; I2 =17.6%). There was substantial and consistent evidence of elevated anal SCC incidence in SOTR

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites

Clinical performance of methylation as a biomarker for cervical carcinoma in situ and cancer diagnosis: A worldwide study.

The shift towards primary human papillomavirus (HPV)-based screening has necessitated the search for a secondary triage test that provides sufficient sensitivity to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals. We evaluated the performance of the previously described DNA-methylation test (S5) in detecting CIN3 and cancers from diverse geographic settings in high-, medium- and low-income countries, using the cut-off of 0.80 and exploratory cut-offs of 2.62 and 3.70. Assays were performed using exfoliated cervical specimens (n = 808) and formalin-fixed biopsies (n = 166) from women diagnosed with cytology-negative results (n = 220), CIN3 (n = 204) and cancer stages I (n = 245), II (n = 249), III (n = 28) and IV (n = 22). Methylation increased proportionally with disease severity (Cuzick test for trend, P < .0001). S5 accurately separated women with negative-histology from CIN3 or cancer (P < .0001). At the 0.80 cut-off, 543/544 cancers were correctly identified as S5 positive (99.81%). At cut-off 3.70, S5 showed a sensitivity of 95.77% with improved specificity. The S5 odds ratios of women negative for cervical disease vs CIN3+ were significantly higher than for HPV16/18 genotyping at all cut-offs (all P < .0001). At S5 cut-off 0.80, 96.15% of consistently high-risk human papillomavirus (hrHPV)-negative cancers (tested with multiple hrHPV-genotyping assay) were positive by S5. These cancers may have been missed in current primary hrHPV-screening programmes. The S5 test can accurately detect CIN3 and malignancy irrespective of geographic context and setting. The test can be used as a screening and triage tool. Adjustment of the S5 cut-off can be performed considering the relative importance given to sensitivity vs specificity

The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting

We assessed the cost-effectiveness of including boys vs girls alone in a pre-adolescent vaccination programme against human papillomavirus (HPV) types 16 and 18 in Brazil. Using demographic, epidemiological, and cancer data from Brazil, we developed a dynamic transmission model of HPV infection between males and females. Model-projected reductions in HPV incidence under different vaccination scenarios were applied to a stochastic model of cervical carcinogenesis to project lifetime costs and benefits. We assumed vaccination prevented HPV-16 and -18 infections in individuals not previously infected, and protection was lifelong. Coverage was varied from 0-90% in both genders, and cost per-vaccinated individual was varied from I$25 to 400. At 90$50, vaccinating girls alone was <$200 per year of life saved (YLS), while including boys ranged from$810–18 650 per YLS depending on coverage. For all coverage levels, increasing coverage in girls was more effective and less costly than including boys in the vaccination programme. In a resource-constrained setting such as Brazil, our results support that the first priority in reducing cervical cancer mortality should be to vaccinate pre-adolescent girls

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

To investigate the prevalence of, and risk factors for, cervical infection with human papillomavirus (HPV) in Shenyang City, People's Republic of China, we interviewed and obtained cervical cell samples from 685 women aged 15–59 years enumerated from local population lists. Human papillomavirus DNA was detected in cervical cell samples using a GP5+/6+-based PCR assay for 44 HPV types. Human papillomavirus prevalence was 16.8% overall and 13.6% among women without cervical abnormalities (16.6% and 12.4%, respectively, age-standardised to the world standard population), with no significant trends in HPV prevalence by age group. Of the 32 types identified, high-risk HPV types predominated in all age groups, HPV16 being the most common (3.4% of all women), followed by HPV52 (2.5%) and 58 (1.9%). Multiple-type infections accounted for 31.3% of all infected women. Not being married, reporting multiple sexual partners and husband's extramarital sexual relationships were all significantly associated with being HPV-positive. The disclosure of a relatively high HPV prevalence in Shenyang, in comparison with other worldwide populations, raises important questions concerning the prevention of cervical cancer in China, especially given the promising efficacy of prophylactic HPV vaccines

Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands

We present the type-distribution of high-risk human papillomavirus (HPV) types in women with normal cytology (n=1467), adenocarcinoma in situ (ACIS) (n=61), adenocarcinoma (n=70), and squamous cell carcinoma (SCC) (n=83). Cervical adenocarcinoma and ACIS were significantly more frequently associated with HPV18 (ORMH 15.0; 95% CI 8.6–26.1 and 21.8; 95% CI 11.9–39.8, respectively) than normal cytology. Human papillomavirus16 was only associated with adenocarcinoma and ACIS after exclusion of HPV18-positive cases (ORMH 6.6; 95% CI 2.8–16.0 and 9.4; 95% CI 2.8–31.2, respectively). For SCC, HPV16 prevalence was elevated (ORMH 7.0; 95% CI 3.9–12.4) compared to cases with normal cytology, and HPV18 prevalence was only increased after exclusion of HPV16-positive cases (ORMH 4.3; 95% CI 1.6–11.6). These results suggest that HPV18 is mainly a risk factor for the development of adenocarcinoma whereas HPV16 is associated with both SCC and adenocarcinoma

Prevalence of human papillomavirus infection in women in Benin, West Africa

<p>Abstract</p> <p>Background</p> <p>Cervical cancer ranks as the first most frequent cancer among women in Benin. The major cause of cervical cancer now recognized is persistent infection of Human Papillomavirus (HPV). In Benin there is a lack of screening programs for prevention of cervical cancer and little information exists regarding HPV genotype distribution.</p> <p>Methods</p> <p>Cervical cells from 725 women were examined for the presence of viral DNA by means of a polymerase chain reaction (PCR) multiplex-based assay with the amplification of a fragment of L1 region and of E6/E7 region of the HPV genome, and of abnormal cytology by Papanicolaou method. The association between HPV status and Pap test reports was evaluated. Socio-demographic and reproductive characteristics were also related.</p> <p>Results</p> <p>A total of 18 different HPV types were identified, with a prevalence of 33.2% overall, and 52% and 26.7% among women with and without cervical lesions, respectively. Multiple HPV infections were observed in 40.2% of HPV-infected women. In the HPV-testing group, the odds ratio for the detection of abnormal cytology was 2.98 (95% CI, 1.83-4.84) for HPV positive in comparison to HPV negative women. High risk types were involved in 88% of infections, most notably HPV-59, HPV-35, HPV-16, HPV-18, HPV-58 and HPV-45. In multiple infections of women with cytological abnormalities HPV-45 predominated.</p> <p>Conclusions</p> <p>This study provides the first estimates of the prevalence of HPV and type-specific distribution among women from Benin and demonstrates that the epidemiology of HPV infection in Benin is different from that of other world regions. Specific area vaccinations may be needed to prevent cervical cancer and the other HPV-related diseases.</p