| BackgroundCervical cancer is one of the most health-threatening diseases in female. It takes about more than 5 ～10 years to develop from cervical intraepithelial neoplasia (CIN) to invasive cancer, which provides an opportunity for early detecting, diagnosing cervical precursors and early invasive lesion, timely treating and blocking the progress of disease. Since the 1960s, with multiple methods for cervical cancer screening and diagnostic techniques have been unceasing enhancement, its morbidity and mortality worldwide, including the economic developed and developing countries, are significantly reduced. The incidence of cervical cancer in China has decreased from 14.6/100000 to 4.3/100000 in recent twenty years. National Health Service(NHS) reported that during 1989 to 2009/2010, incidence rates of cervical cancer decreased from 15.0 to 9.8 per 100000 female population, over a third. Meanwhile the mortality reduced by sixty percentage,from 5.8/100000 to 2.2/100000 female population over the past 20 years.Generally, the Pap smear or other cytological method is used as the primary test for cervical cancer screening programs. A positive cytological result will refer to colposcopic examination and directed biopsies of obvious lesions when necessary, then the biopsies diagnosed as CIN2 or worse (>CIN2) or CIN1 sometimes lead patients to treatment. Therefore evaluating cervical cytology results adequately has a guiding significance for cervical cancer screening and management. In which, the cytology result of high grade squamous intraepithelial lesion (HSIL) should be paid great attention to. According to the 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors, HSIL on cytology demonstrates women at great risk. CIN2+ is found at colposcopy in about sixty-percentage of women with HSIL and cervical cancer is in around 2%. While women with HPV-positive HSIL co-test results, the 5-year risk of CIN3+is 50% and 5-year cancer risk reaches to 7%. Considering such worries, most women with HSIL on cytology will choose to deal with cervical lesions, except for pregnant women or young teenagers, in order to heal or rule out occult cancer lesions in further. There are two categories of the treatment for cervical lesions, one is ablation and the other is excision. The former destructs the cervical lesion by various physical means of laser, electrocautery, frozen and microwave to therapeutic purposes. Although easily operation and less impact on the shape and structure of the cervix, ablation is at risk of misdiagnosis and mistreatment because it cannot provide a living tissue specimens for definitive pathology assessment. So the ablation therapy has been gradually reducing in the treatment of cervical intraepithelial neoplasia, instead cervical excision is a more widely used method. Loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC) are common techniques for cervical excision, both of which can not only provide tissues for pathological diagnosis, but also completely removal of diseased cervical tissue for treatment.Previous researches found that the rates of no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2-3 or above were 4.0～7.2%,4.0～16.0% and 79.0～88.7% respectively in the histopathological diagnosis of excision specimens for women with HSIL cytology result. That means only about eighty percentage women with HSIL on cytology really need to be intervened. Because of different over treat standards, the ratio of over-treatment on cytological HSIL varied from 2.8～39% in ever reports. Excessive handling HSIL on cytology result may lead to several problems as following. Firstly, the secondary surgical procedure will become more difficult. It has been reported that the rate of positive margin, residual disease and recurrence after cervical conization was high. It is possible for some patients to have a second operation of repeating cervical excision or fascia hysterectomy and even radical hysterectomy. Some studies reported that the risk of recurrence is about 8 ～ 14% with LEEP technique and is not modified whether the margins are involved or not. As the residual cervical tissues reduction, it’s hard to expose cervical lesions during the second surgery, which increase the incidence of damage to cervical surrounding structures, even excessive treatment again. Would repair, peripheral vascular proliferation and tissue adhesion after initial conization will also account for the high risk of hemorrhage during perioperative period. Secondly, the short-term or long-term complications of cervical conization are not determined. Some studies found that bleeding and infection occurred after cervical excisions respectively 5.2～7.9%, 3.1～3.5%. Also other potential complications including cervical stenosis, scar formation and amenorrhea or cervical endometriosis were reported before. Thirdly, the impacts of cervical conization on pregnancy and delivery were still unclear. It is assumed that excision results in cervical tissues shorten and mucus secretion reduced, which may interfere with the sperm capacitation that causes of some infertility. During pregnancy, reduction in cervical mucus will affect the local defensive immune system, increasing the reproductive tract infections and causing inflammation, which will lead to the rupture of membrane, early miscarriages and preterm deliveries. Meanwhile, the supporting role for progress pregnancy will decrease compared with pre-operation of cervical conization with varying degree of the cervix shortening, as well as scar formation. Consequently, it’s likely to increase adverse obstetrical complications of late abortion, premature labors, urgent production and neonatal low-birth weight. According to a system review on large sample size that the preterm birth rate was 12.6% and low-birth weight rate was 10.9% after LEEP surgery. Finally, psychological pressures and the cost burden of treatment deserve concerns. For a portion of women with HSIL on cytology, especially patients whose lesions will be fading during the follow-up, cervical excision was undoubted over treated. Their anxiety and worries caused by various examination results also should not be ignoring. And unnecessary interventions will produce heavy economic pressure. Reported in Fung’study, the cost of inappropriate surgery by loop electrosurgical excision procedure is estimated to be more than 550$ dollars each person over-treated. Therefore, it’s necessary to find out potential risk factors of over-treating for women with HSIL on cytology and guide clinical rational effective corresponding management.ObjectiveTo explore the possible influencing predictors for overtreatment on women as newly diagnosed HSIL cytological result and provide specific individual clinical decisions with theoretical basis. Diagnosing and healing of high-risk populations timely and appropriately, thus effective in preventing cervical cancer.Methods(1)study objects:Collected medical data in 227 cases of non-pregnant women with newly diagnosed HSIL on cytology, followed by cervical conization at the department of gynecology in our hospital between January 2009 and December 2013. All of the patients were ruled out cervical carcinoma grossly under colposcopy and signed the informed consent before treatment.(2)study parameters:Patients’information were abstracted including the age, menstrual status (menopause or not), the viral load of high risk HPV-DNA, colposcopic examination, cervical conization methods and the results of histopathology on living specimens, as well as whether to biopsy before conization or not. Set the final histological diagnosis less than low grade squamous intraepithelial lesion (LSIL) as overtreatment, which included CIN1 and no CIN. Analyzed the relationships between above factors and the overtreatment rate, then found out risk predictors.(3)examination standards:All results of cervical cytology were obtained using Thinprep Cytlogic Test (TCT, Hologic 1996) and interpreted by pathological cytology specialist physicians according to 2001 the Bethesda System. With Hybrid Capture 2 technique, the viral load of high risk HPV-DNA was determined. And the positive standard was defined RLU/CO as more than lpg/ml. Colposcopic examination was conducted by skilled doctors, using the electronic colposcope imaging system of SLC 2000 (Shenzhen Jinkewei Company). Diagnosis were made on the basis of 2011 Colposcopic Terminology of the International Federation for Cervical Pathology and Colposcopy. Histopathology results, referred to the Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations From the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology, were divided into 2-tiered system that applied terms CIN1 to low-grade squamous intraepithelial lesion and CIN2,3 to high-grade squamous intraepithelial precursors.(4)statistical methods:Frequency distribution were calculated for each variable. Data processing and statistical analysis with computer software SPSS 17.0, univariate analysis using Fisher Exact test or Nonparametric test. Incorporating the meaningful factors, whose P values were less than 0.1, into the Binary logistic regression to find out indicative factors. Defined this P-value was less than 0.05 (two-tailed) as significant statistically. Recorded odd ratio (OR) value and 95% confident interval(CI) as well.ResultsThe final tissue pathological diagnosis confirmed no CIN, LSIL and HSIL were detected in 9(4.0%),13(5.7%) and 199 (87.7%) cases, thus the overtreatment of HSIL on cytology was 9.7% (22/227). Four of the histological HSIL women were diagnosed as cervical squamous carcinoma in situ (CIS) and one was adenocarcinoma in situ (AIS). In a total of five women were detected as squamous carcinoma of cervix (SCC). Univariate analysis showed that patient’ age, menstrual status, treatment protocol and cervical conization methods were no obvious relation to the overtreatment of cytological HSIL. But colposcopic examination and the viral load of hr-HPV-DNA might be the predictive factors (both P-values were less than 0.1). By further binary logistic regression analyzed, colposcopic examination was a protective factor for overtreatment of HSIL on cytology (P=0.038). When divided colposcopic examination images into normal impression group, low grade lesion group and high grade lesion group, then reference to the normal impression, the OR values were respectively 0.165 (95% CI0.029～0.946)、0.113 (95% CI0.021～0.601).And the viral load of high risk HPV-DNA also acted as a protective factor for avoiding excessive intervention on cytological HSIL (P=0.020). Making the viral load of high risk HPV-DNA into<100pg/ml、100～1000pg/ml、≥1000pg/ml three groups and < 100pg/ml as reference, then the OR values were 0.150 (95% CI0.039～0.570) 0.735 (95% CI0.216～2.504)ConclusionsThe viral load of high risk HPV-DNA and colposcopic examination were both the significant predictors for overtreatment ratio of HSIL on cytology. When the colposcopic examination suggesting the severity of disease progress, the overtreatment rate of cytological HSIL will decrease. And the viral load of high risk HPV-DNA ranging from 100 to 1000 pg/ml can contribute to avoid overtreatment of HSIL on cytology. But we did not find the trend that the overtreatment rate of cytological HSIL gradually declined with the rise of the viral load of high risk HPV-DNA. Considering possible risks resulted from cervical conization procedure for pregnancy in future, we still recommended young women desiring fertility with conservative "three steps" protocol. |
PDF Full Text Request