BV is a common, treatable condition resulting from replace- ment ofthe normal hydrogen peroxide-producing Lactobacillus- predominant vaginal flora with anaerobic bacteria, e.g. Gard- nella vaginalis, Mobiluncus species and Mycoplasma hominis. 5 Factors that increase the risk of BV are cigarette smoking, the use of intrauterine devices, frequent douches, multiple sexual partners, and early age at first intercourse. BV is known to be associated with many obstetric and gynecologic complica- tions such as preterm labor and delivery, chorioamnionitis, post-cesarean endometritis, pelvic inflammatory disease (PID), postabortal PID, postoperative cuff infections after hyster- ectomy, and a possible connection with abnormal cervical cy- tology and CIN. 6-10
We also observed that high HPV viral loads were associated with LVSI and deep stromal invasion, which have been previ- ously reported to be correlated with poor prognosis [20-23].
However, this result seems to conflict with our finding that high HPV viralload was associated with improved DFS. Few previous studies have reported the correlations of pretreat- ment HPV viralload with clinicopathologic characteristics and prognosis in cervical cancer patients. Kim et al.  performed a prospective study that recruited 169 cervical cancer patients treated with radiation therapy. The researchers classified their patients into low- or high-HPV viralload groups based on a median value of 385.8 RLU/CO. The study found that HPV viralload was associated with age, histologic type, and lymph node metastasis. Additionally, low HPV viralload was associ- ated with poor radiotherapy outcome. Kim et al.  reviewed 34 early-stage cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy and placed the patients in arbitrary groups based on HPV viralload at 100 RLU/CO. The researchers reported that HPV viralload was not associated with any clinicopathologic characteristics or with prognosis. Consequently, the correlations of pretreatment HPV viralload with clinicopathologic characteristics and prog- nosis in cervical cancer patients reported in previous studies were inconsistent, theassociationof pretreatment HPV viralload with other prognostic factors is currently unclear.
Objective: To assess theassociation between condom use and oral contraceptive consumption andthe risk ofcervicalintraepithelialneoplasia (CIN).
Methods: A cross-sectional study was conducted in Perth clinics. A total of 348 women responded to the structured questionnaire. Information sought included demographic and lifestyle characteristics such as the use of condom for contraception, consumption of oral contraceptive, and duration of oral contraceptive usage. Crude and adjusted odds ratio (OR) and associated 95% confidence interval (CI) were calculated using unconditional logistic regression models and reported as estimates ofthe relative risk.
0.268). There was no association between the HR-HPV test result and resection margin status (p=0.821).
Univariate analysis showed that age, body mass index, men- opausal status, parity, marital status, alcohol consumption, smoking habits, medical disease, scholastic ability, method of conization, grade of dysplasia, and glandular extension were not risk factors for recurrent cytological or pathological ab- normalities.
analysis was performed to find out which parameter was associated with CIN persistence/
recurrence among 100 patients, but any parameter did not show a statistical significant association. As a result, age, parity, initial HPV load, colposcopy-directed biopsy, type of conization, conization pathology, conization depth, glandular involvement, and margin status were all well-balanced between the 2 groups. We analyzed PD-L1 and PD-L2 expression in the dysplastic squamous epithelium and PD-1 expression in the TILs by IHC in FFPE tumor specimens ofthe 100 patients (50 patients with persistence/recurrence, 50 patients without persistence/recurrence). The patient demographics and clinicopathological characteristics and their correlations with protein expression are summarized in Table 4. Representative IHC images are shown in Fig. 1. Of the 100 cases, 39 had glandular involvement, 20 cases from recurred patients, and 19 cases non-recurred. The mean depth of glandular involvement was 1.12 mm. The volume of CIN was estimated by the number ofcervical quadrants. In 18 cases, the involved number of quadrants could not be determined due to fragmentation of tissue. One quadrant was involved by dysplasia in 25 cases, 2 quadrants in 24, 3 quadrants in 21, and 4 quadrants in 12 cases. None ofthe cases expressed PD-L1. PD-1 was expressed on TILs with a membranous pattern. PD-1+ TILs were observed in 25 of 100 patients (25%; 95%
Objective: In cervicalintraepithelialneoplasia (CIN), p16 INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about theassociation between the p16 INK4a immunohistochemistry andthe outcomes of CIN. Here, we report p16 INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN.
Methods: p16 INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis ofthe medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16 INK4a expression andthe outcomes. We also performed HPV genotyping and analyzed the relation between the infecting humanpapillomavirus (HPV) genotype andthe outcomes.
cytology prior to biopsies. Sera from the normal group were collected after examining hysterectomy specimens.
Individuals with negative results in the examination of hema- toxylin and eosin‐stained sections of hysterectomy specimens were classified as a normal group. Sera from the CIN I group were collected immediately after punch biopsy, and those from the CIN II and CIN III groups were collected before large loop excision ofthe transformation zone. Sera from cer- vical cancer patients were collected before surgery. Women over age 20 who have resulted with an abnormality in the cervix from the cytology examination and are designed for biopsy or surgery under suspicion of CINs or cervical cancer were included. Immunocompressed individuals (infection with human immunodeficiency virus, transplant operation, or immunocompressive medications) or individual who has record of another type of cancer was excluded.
Why has VAIN been overlooked so far? Is it because ofthe difficulty of colposcopic assessment ofthe lesions? Perhaps because the so-called flat condyloma might have been ne- glected? The true reason may well be a cytological screening artifact since cytological smears are usually taken from the cervix but not from the vagina. To recognize VAIN with cer- tainty, it is useful to look for HPV DNA in vaginal smears. The natural history of VAIN 1-3 andthe risk of progression to in- vasive vaginal carcinoma remain poorly defined. The immedi- ate importance of VAIN might be its role as a viral reservoir for potential sexual transmission. Therefore, it is important to recognize and monitor VAIN to control lower genital tact neoplasia.
histological assessment of section margin, diagnostic accuracy of treatment failure, etc.).
In addition, the heterogeneity ofthe included studies may be greater than that of previous pooled analyses because ofthe relatively wide inclusion criteria of this present review.
Therefore, our pooled analysis was still insufficient to establish detailed follow-up algorithms for women treated for CIN 2/3. However, despite these limitations, we attempted a pooled analysis because ofthe lack of RCTs andthe relatively small size of previous meta-analyses evaluating the posttreatment performance of HPV testing. A recent meta-analysis of eight well-designed studies indicated that high-risk HPV testing has a higher sensitivity compared with cytology in detecting posttreatment CIN 2+, and a similar specificity . However, the number of women included in this meta-analysis was relatively small (n=1,512), and >50%
I. 서 론
자궁경부암은 지난 몇 십 년 동안 선별검사를 통해서 우리나라를 비롯한 서 구 선진국가에서 사망률이 많이 감소하였다. 이러한 선별검사의 목적은 자궁경 부의 전암 병변을 조기 발견하여 침윤암으로 발전되기 전에 치료를 하고 이미 치료된 병변의 재발을 조기 발견하여 적절히 치료하는 것이다. 과거에는 자궁경 부 세포검사를 선별검사로 주로 사용하였다. 그러나, 인유두종바이러스 (HPV)의 지속적인 감염이 자궁경부암의 발생과 연관이 있다는 것이 밝혀지고 (Human papillomavirus, 1995; Walboomers 등, 1999; Bosch 등, 1995), 자궁경부암 환자에서 인유두종바이러스의 이환율이 100%에 이르기 때문에 최근에는 인유두종바이러 스 검사가 자궁경부암 선별검사로써 중요한 부분을 차지하고 있다.
genes. In tumors with a lower rate of integration, therefore, theviral genome must remain extra chromosomally which would provide a mechanism for expression ofthe late viral genes. 37,38 Thus, a relationship between the presence of capsid antibodies andthe time elapsing before integration of HPV DNA in different subsets of tumors may explain theassociation between HPV serology and prognosis. Another similar study involving 150 cervical cancer patients by Skiba et al. reported that anti-HPV16 seropositivity correlated with prolonged, progression-free and overall survival in the FIGO stage 1 and 2 patients. They hypothesized that the seronegative patients had reduced HPV-specific immune competence, so that the virus might have been able to escape both the humoral andthe cellular defense mechanisms, resulting in an impaired ability ofthe immune system to control the HPV-induced tumor. 39,40 The results in this study also revealed a correlation with HPV 16 seropositivity and a better disease free survival supporting the above hypothesis.
In conclusion, the results ofthe present study suggest that low HPV load before conization ofthe cervix is indicative ofthe absence of dysplasia in LEEP specimens. Also, high viralload before conization and margin involvement in LEEP con- ization were significant independent predictors of recurrence after conization. The absence of dysplasia in the LEEP speci- mens was not a predictor of recurrence or a guarantee for no recurrence at follow-up. Close follow-up of cases with no dys- plasia in LEEP specimens is still needed, as it is in other pa- tients who have undergone LEEP.
The introduction ofhumanpapillomavirus (HPV) testing into cervical cancer screening programs has significantly improved the detection of premalignant lesions and continues to improve the detection and prevention of invasive cervical cancer. The results of 4 large trials successfully demonstrated higher detection rates ofcervicalintraepithelialneoplasia (CIN) 3 with HPV-based screening compared to cervical cytology [1-5], and a recent meta- analysis of long term follow up in those trials demonstrated 60% to 70% greater protection against invasive cancer compared to cytology screening . While the role of HPV screening is well established with well-conducted randomized controlled trials, there are fewer consensuses regarding the utility of HPV testing after treatment for premalignant cervical lesions. Typically, CIN 2/3 lesions are treated with excisional or ablative procedures, and post-treatment these women are then entered into more intensive surveillance protocols.
In a prospective follow-up study, while the cumulative inci- dence ofcervicalintraepithelialneoplasia 3 (CIN3) was 4.4%
among HR-HPV positive women followed-up for up to 45 mon- ths, it was only 0.24% among HR-HPV negative women. 3 HR- HPV DNA testing has potential clinical applications, especial- ly in women with atypical squamous cells of undetermined sig- nificance (ASC-US), 4 postmenopausal women with low-grade squamous intraepithelial lesion (LSIL), 5 follow-up of adolescents with LSIL, 6 post-colposcopy follow-up, 7 and post-treatment fol- low-up of high-grade CIN. 8 The American Cancer Society has recommended HPV DNA testing in conjunction with cytolo- gy as a screening option for women aged 30 years and older, 6 and has developed guidelines for use ofthe prophylactic HPV vaccine in the prevention of CIN andcervical cancer. 9 Consid- ering these findings and recommendations, HR-HPV testing could have important roles in the management of women with abnormal cytology, primary cervical cancer screening, andthe development of HPV vaccines.
Yong Mi Kim, Jin Young Park, Kyung Mi Lee, Tae-Wook Kong, Seung-Chul Yoo, Woo Young Kim, Jong-Hyuck Yoon, Suk-Joon Chang, Ki-Hong Chang, Hee-Sug Ryu
Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
Objective: Recent data suggest that pretreatment HPV (Human papillomavirus) viralload is useful to predict the severity ofintraepithelial lesions ofthe uterine cervix and formulate a treatment plan. However, the relationship between initial HPV viralloadand prognosis ofcervical cancer patients has not yet been clearly defined. The objective of this study was to determine whether HPV viralload has prognostic significance in patients with early stage cervical carcinoma treated by surgery.
578 (56.3%) with ASCUS and 449 (43.7%) with LSIL. The follow-ups, with results of cytology and HPV DNA testing, were included in the final analysis. We analyzed the cytological and histological data obtained from each follow-up, which took place at 6-month intervals.
Demographic and behavioral information was obtained via self-administered questionnaires and interview surveys every year. Enrolled participants who were diagnosed with a lesion classified as more severe than cervicalintraepithelialneoplasia 2 (CIN 2+) by colposcopically directed biopsy were not followed up further in the course of this study. Based on
MATERIALS AND METHODS
1. Study population
A total of 18,170 women aged 17 to 83 years who visited a large private healthcare company consisting of 7 centers nationwide from January 2014 to December 2016 were included in this study. All patients underwent a gynecologic examination that included collection of a cervical sample for HPV DNA genotyping andcervical cytology via a Papanicolaou- stained conventional smear. Abnormal cytology was reported by pathologists according to the 2001 Bethesda system . The samples were classified as: atypical squamous cells of undetermined significance (ASCUS); atypical squamous cells-cannot exclude high-grade squamous intraepithelialneoplasia (ASC-H); low-grade squamous intraepithelialneoplasia (LSIL); high-grade squamous intraepithelialneoplasia (HSIL); atypical glandular cells (AGC);
Objective : To evaluate the utility ofhumanpapillomavirus (HPV) DNA detection, we conducted a study to determine accuracy of Hybrid capture test kit for detection ofcervicalintraepithelialneoplasiaand cancer by biopsy results.
Methods : We enrolled women referred to a colposcopy clinic. All 2010 women had a sample for HPV DNA test and underwent colposcopically directed biopsies or loop electrode excision procedure. We used the Hybrid capture I test kit for HPV testing.
In conclusion, the HR-HPV genotype is a reliable prognostic marker of residual disease following a LEEP for CIN 3, and is more accurate than the HPV viralload, endocervical cytology, or cone margin status at the time ofthe LEEP. Although this finding requires substantiation in a further large-scale prospective investigation using standardized PCR- techniques for HPV detection, HPV-16 and HPV-18 should be considered as a risk factor for residual disease after a LEEP for CIN 3 and such patients warrant special attention with compulsive follow-up.
In our study, we found that the incidence rate and medical costs related to CIN differ by age.
To effectively implement secondary prevention strategies against cervical cancer within a limited budget, age-specific strategies should be more closely studied in the future.
This study has a few limitations. First, because we carried out this research relying on somewhat unclear disease codes andthe number of claims provided by the HIRA service, it is highly likely that there are duplicated or false claims, and that the actual residence address may be different from the registered address. For example, since the incidence rate was calculated by excluding the previous year's claimants only, patients with cervical cancer who were assigned accurate disease codes may have been included twice in our data if they were diagnosed 2 years previously and, in addition, obtained healthcare for their condition within those 2 years. There is also a high potential that cervical cancer will recur, but this would not have a large influence on the comparison of incidence rates over the course of 5 years.