Can we increase the cervical cancer screening interval with an HPV test for women living with HIV? Results of a cohort study from Maharashtra,India

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.     

HPV-mRNA and HPV-DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri

Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at −80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5–7 years later were comparable [76.3% (95% CI: 65.8%–84.3%) and 82.5% (95% CI: 72.6%–89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95–99.98) and 99.98% (95% CI: 99.96–99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.     

CyclinA1 Promoter Methylation in Self-Sampling Test

Background: Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test.  Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods: A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled.  Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure  was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results: Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its  specificity and accuracy were 99.5% and 82.14%, respectively.  The sensitivity of SS-HPV was 70.5%, and its  specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion:  Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.     

HPV vaccination and cancer prevention

Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.     

The possible association between the presence of an MPO −463 G > A (rs2333227) polymorphism and cervical cancer risk

Purpose

The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer.

Host control of human papillomavirus infection and disease

Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state.     

派特灵治疗宫颈高危型人乳头瘤病毒感染的临床观察

目的探讨派特灵在高危型人乳头瘤病毒（HPV）感染的宫颈病变患者中的临床价值。方法2009年6月至2011年6月在南通市妇幼保健院宫颈门诊行宫颈高频电刀电圈切除术治疗，病理学诊断为宫颈上皮内瘤变Ⅱ-Ⅲ级，术后6个月细胞学、阴道镜检查正常而高危型HPV检测阳性未自然转阴患者40例，随机分为治疗组及对照组；治疗组给予派特灵局部上药，对照组不再进行任何干预治疗。停药3、6个月后再次进行细胞学及高危型HPV—DNA检测。结果治疗组停药3、6个月后抗HPV感染的总有效率为90．0％、90．0％，对照组总有效率分别为30．0％、35．0％，治疗组的疗效明显高于对照组（∥分别为3．779、3．751，均P〈0．01），3个月及6个月后治疗组HPV—DNA负荷量均较治疗前明显下降（‰分别为3．606、4．365，均P〈0．01），对照组无明显疗效（U0分别为0．947、1．407，均P0〉0．05），治疗HPV负荷的改善率明显高于对照组（U。=3．653，U2=3．147，均P〈0．01）。结论派特灵可用以治疗高危型HPV感染。     

被动吸烟和宫颈疾病的相关研究

目的:探讨被动吸烟与宫颈癌、宫颈上皮内瘤变(CIN Ⅰ~Ⅱ)发病的相关性。方法:回顾性研究被确诊并收治的原发性浸润性宫颈癌新发病例192例(宫颈癌组),CIN Ⅰ~Ⅱ 142例(CIN组),正常对照组254例(对照组),进行一对一的问卷调查,运用χ2检验和Logistic回归分析对被动吸烟与宫颈疾病发病的相关性进行分析。结果:无论是距诊断或就诊前近10年内还是10年以前,患病组和对照组是否被动吸烟、被动吸烟的持续时间、接触强度都有显著差别(P<0.01)。Logistic回归分析结果显示10年内被动吸烟时间是宫颈癌和CIN Ⅰ~Ⅱ发病危险因素,分娩次数和肿瘤家族史是CIN Ⅰ~Ⅱ的危险因素,高教育程度和年龄低是保护因素。结论:被动吸烟及接触时间、强度是宫颈疾病发病的相关危险因素。