The accuracy of cervical cancer and cervical intraepithelial neoplasia diagnosis with loop electrosurgical excisional procedure under colposcopic vision

Objective

The colposcopic vision guided loop electrosurgical excisional procedure (LEEP) was studied for the effective diagnosis of cervical cancer and cervical intraepithelial neoplasia (CIN).

Methods

A total of 199 patients participated in this study. Individual cases were from gynecologic outpatients at Thammasat University Hospital, Thailand. These had diagnoses for CIN and were selected for treatment with colposcopic guided LEEP. The average age of patients in this study was 45. Menopausal women represented 31%, (61/199) of the patients. The most frequently found Pap smear result among these women (44%, 88/199), was that of high-grade squamous intraepithelial lesion. The next most frequent Pap smear result (32%, 64/199) was low-grade squamous intraepithelial lesion. Patients'' medical records and outcomes were evaluated for consistency of pathological examination between colposcopic directed biopsy and LEEP. Discrepancies between initial diagnosis and the final diagnosis were also analyzed.

Results

The colposcopic guided LEEP accurately determined 100% of the cervical cancer cases and 84.8 % of the high-grade squamous intraepithelial lesion cases. Involvement of the ectocervical or endocervical margin regions was found to be 5% and 10% respectively, in this study. Excessive bleeding complication, either during the excision and/or postoperative recovery was found in 3% and 6% of cases, respectively.

Conclusion

LEEP under colposcopic vision is a recommended technique for ambulatory management of precancerous lesion and early diagnosis of cervical cancer. This technique significantly reduces rate of positive ectocervical cone margin involvement.     

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High‐Grade Squamous Intraepithelial Lesion

Background.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results.

Materials and Methods.

A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013.

Results.

ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status.

Conclusion.

If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.

Implications for Practice:

Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.     

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear

Objective

To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology.

Methods

Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold.

Results

Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively.

Conclusion

VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.     

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities

Background:

Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC.

Methods:

All vulvar SCCs (201) were classified to be dVIN- (n=164) or uVIN related (n=37). Data with regard to the smear history and cervical histology were retrieved from PALGA, the nationwide Netherlands database of histo- and cytopathology. For HSIL cervical smears of which histology was taken, HPV DNA analysis on both the vulvar and cervical specimens was performed.

Results:

At least one smear was available in 145 (72%) of the 201 patients. Patients with a uVIN-related vulvar SCC more often had an HSIL compared with patients with a dVIN-related SCC (35 vs 2%, P<0.001). A total of 10 of the 13 HSILs were histologically assessed and identical HPV types were found in the vulva and cervix.

Conclusion:

These data emphasise the necessity to differentiate between dVIN- and uVIN-related vulvar tumours and to examine the entire lower female ano-genital tract once an uVIN-related lesion is found.     

The utility of the human papillomavirus DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia

Objective

We evaluated the human papillomavirus (HPV) DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia (VAIN).

Methods

A retrospective review of the medical records of patients with a pathological diagnosis of VAIN was performed. Eligible women (N=48) were followed for cytology and HPV DNA test, and colposcopic biopsies were taken at 3- to 6-month intervals. Thirty-seven patients were followed for more than 6 months; their HPV DNA test results were compared to the cytology results for the prediction of disease prognosis.

Results

The degree of VAIN was more severe in patients with a high initial HPV DNA load (p=0.009). Patients with VAIN 2 and VAIN 3 were older than those with VAIN 1 (p=0.005 and 0.008, respectively). In 26 out of 37 patients (70.3%), the VAIN resolved. The other patients had persistent lesions with no progression to invasive vaginal carcinoma. The last follow-up HPV DNA load was significantly higher in the group with persistent VAIN compared to the group with resolved VAIN (p<0.0001). Negative cytology was observed in 25 out of 26 patients in the VAIN resolved group and in nine out of 11 patients in the VAIN persistent group (p=0.205).

Conclusion

These results suggest that the HPV DNA test, especially for viral load, was more effective for the diagnosis and prediction of persistent VAIN than cytology.     

Application of HPV DNA Testing in Follow-up after Loop Electrosurgical Excision Procedures in Northern Thailand

Background: HPV DNA testing has been recently introduced as an adjunct test to cytology in the follow-up ofpatients after treatment for cervical lesions using the loop electrosurgical excision procedure (LEEP). The aim ofthis study was to evaluate the role of HPV testing in the detection of persistent or recurrent disease after LEEP inpatients with cervical epithelial lesions in northern Thailand. Materials and Methods: Patients who underwentLEEP as a treatment for histological low-grade (LSIL) or high-grade squamous intraepithelial lesion (HSIL)or worse at Chiang Mai University Hospital between June 2010 and May 2012 were included. Follow-ups werescheduled at 6-month intervals and continued for 2 years using co-testing (liquid-based cytology and HybridCapture 2 [HC2]) at 6 months and 24 months and liquid-based cytology alone at 12 and 18 months. Results: Of98 patients included, the histological diagnoses for LEEP included LSIL in 16 patients, and HSIL or worse in82 patients. The LEEP margin status was negative in 84 patients (85.7%). At follow-up, 10 patients (10.2%) hadpersistent/recurrent lesions; 4 among LSIL patients (25.0%) and 6 in the group with HSIL or worse (7.3%). Only2 of 82 patients (2.4%) with HSIL or worse diagnoses had histological HSIL in the persistent/recurrent lesions.Using histologically confirmed LSIL as the threshold for the detection of persistent/recurrent disease, cytology hada higher sensitivity than HC2 (90.0% versus 70.0%). At the 6-month follow-up appointment, combined cytologyand HC2 (co-testing) had a higher sensitivity in predicting persistent/recurrent disease (80.0%) compared withthat of cytology alone (70.0%) and HC2 (50.0%). Conclusions: After LEEP with a negative surgical margin, therate of persistent/recurrent lesions is low. The addition of HPV testing at the 6-month visit to the usual cytologyschedule may be an effective approach in the follow-up after LEEP.     

HPV infection in women with and without cervical cancer in Conakry, Guinea

Background:

Cervical cancer incidence in western Africa is among the highest in the world.

Methods:

To investigate human papillomavirus (HPV) infection in Guinea, we obtained cervical specimens from 831 women aged 18–64 years from the general population of the capital Conakry and from 77 locally diagnosed invasive cervical cancers (ICC). Human papillomavirus was detected using a GP5+/6+ PCR-based assay.

Results:

Among the general population, the prevalence of cervical abnormalities was 2.6% by visual inspection and 9.5% by liquid-based cytology. Fourteen of 15 high-grade squamous intraepithelial lesions were visual inspection-negative. Human papillomavirus prevalence was 50.8% (32.1% for high-risk types) and relatively constant across all age groups. Being single or reporting ⩾3 sexual partners was significantly associated with HPV positivity. HPV16 was the most common type, both among the general population (7.3%) and, notably in ICC (48.6%). HPV45 (18.6%) and HPV18 (14.3%), the next most common types in ICC, were also more common in ICC than in HPV-positive women with normal cytology from the general population.

Conclusion:

The heavy burden of HPV infection and severe cervical lesions in Guinean women calls for new effective interventions. Sixty-three per cent of cervical cancers are theoretically preventable by HPV16/18 vaccines in Guinea; perhaps more if some cross-protection exists with HPV45.     

The relationship between positive peritoneal cytology and the prognosis of patients with FIGO stage I/II uterine cervical cancer

Objective

The purpose of this study was to assess whether peritoneal cytology has prognostic significance in uterine cervical cancer.

Methods

Peritoneal cytology was obtained in 228 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics [FIGO] stages IB1-IIB) between October 2002 and August 2010. All patients were negative for intraperitoneal disease at the time of their radical hysterectomy. The pathological features and clinical prognosis of cases of positive peritoneal cytology were examined retrospectively.

Results

Peritoneal cytology was positive in 9 patients (3.9%). Of these patients, 3/139 (2.2%) had squamous cell carcinoma and 6/89 (6.7%) had adenocarcinoma or adenosquamous carcinoma. One of the 3 patients with squamous cell carcinoma who had positive cytology had a recurrence at the vaginal stump 21 months after radical hysterectomy. All of the 6 patients with adenocarcinoma or adenosquamous carcinoma had disease recurrence during the follow-up period: 3 with peritoneal dissemination and 2 with lymph node metastases. There were significant differences in recurrence-free survival and overall survival between the peritoneal cytology-negative and cytology-positive groups (log-rank p<0.001). Multivariate analysis of prognosis in cervical cancer revealed that peritoneal cytology (p=0.029) and histological type (p=0.004) were independent prognostic factors.

Conclusion

Positive peritoneal cytology may be associated with a poor prognosis in adenocarcinoma or adenosquamous carcinoma of the uterine cervix. Therefore, the results of peritoneal cytology must be considered in postoperative treatment planning.     

Absence of dysplasia in the excised cervix by a loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia

Objective

Absence of dysplasia in the excised specimen following loop electrosurgical excision procedure (LEEP) for treatment of cervical intraepithelial neoplasia (CIN) 2/3 is an occasional finding of uncertain clinical significance. We evaluated several factors including age, liquid-based Pap (LBP) test, human papillomavirus (HPV) load before treatment, and HPV typing as predictors for absence of dysplasia. Absence of dysplasia in LEEP specimens was analyzed in terms of factors for recurrent disease after LEEP conization

Methods

In total, 192 women (mean age, 39.3±8.4 years; range, 24 to 70 years) with biopsy-proven CIN 2/3 were treated by LEEP conization. Age, LBP test, histological grade, HPV load, and HPV DNA typing were evaluated as possible predictors of the absence of residual dysplasia or recurrent disease.

Results

Of the LEEP specimens, 34 (17.7%) showed no dysplasia in preoperative biopsies from patients with proven CIN 2/3. Low HPV load (<100 relative light units [RLU]) was significantly related to the absence of dysplasia in LEEP specimens, using logistic regression. Margin involvement and high HPV load (≥400 RLU) were significant factors for recurrence.

Conclusion

Absence of dysplasia in LEEP specimens occurred in 17.7% of our specimens. Prediction of the absence of dysplasia in LEEP specimens was associated with low HPV load. Residual/recurrent disease after LEEP was associated with a positive resection margin and high viral load, and was not associated with absence of dysplasia in LEEP specimens. Even if there is no dysplasia in conization specimens, close follow-up for residual/recurrent disease is needed.     

The clinical performance of APTIMA human papillomavirus and Hybrid Capture 2 assays in the triage of lesser abnormal cervical cytologies

Objective

This study was performed to evaluate the clinical performance of APTIMA human papillomavirus (AHPV) assay and Hybrid Capture 2 (HC2) assay in screening for cervical disease, especially in women with atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL).

Methods

A total of 411 women diagnosed with ASC-US or LSIL were referred and further triaged by HC2 test. Prior to colposcopy, liquid-based cytology specimens were collected for the AHPV assay. Sensitivity and specificity were established based on the histological findings of cervical intraepithelial neoplasia (CIN).

Results

In all 411 subjects, the positive detection rate of AHPV assay was 70.8% (95% confidence interval [CI], 66.4 to 75.2), which was significantly lower than the positive detection rate of 94.9% obtained using HC2 test (95% CI, 92.3 to 96.8). Only one CIN 3-positive case was detected among the 120 AHPV-negative women, which was then confirmed by Pap smear test to be LSIL. The sensitivities of AHPV and HC2 for CIN 3 were similar (94.1% and 100%, respectively). However, AHPV showed a significantly higher specificity than HC2 test (30.2% and 5.3%, respectively; p<0.001).

Conclusion

AHPV assay is effective in identifying CIN 3-positive cases because of its high specificity and lower false-negative rate. The use of AHPV for the triage of ASC-US and LSIL might help to reduce the referral rate of colposcopy during cervical cancer screening.     

Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study

Background:

High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells.

Methods:

Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen.

Results:

Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH).

Conclusion:

The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.     

Cytology of the vulva: feasibility and preliminary results of a new brush

Objective:

Taking a biopsy is a standard procedure to make the correct diagnosis in patients with suspicious premalignant vulvar lesions. The use of a less invasive diagnostic tool as triage instrument to determine whether biopsy is necessary may improve patient comfort especially in patients with chronic vulvar disorders that may warrant consecutive biopsies. This study was conducted to investigate whether vulvar brush cytology is feasible and may be used to detect (pre)malignant vulvar lesions.

Methods:

A pilot study was performed with patients having clinically normal vulvar skin, lichen sclerosus (LS), usual or differentiated vulvar intraepithelial neoplasia or squamous cell carcinoma. A total of 65 smears were taken with the use of a vulvar brush and biopsies were performed for histopathological analysis.

Results:

Out of 65 smears, 17 (26%) were discarded because of poor cellularity. A total of 28 of 29 (97%) smears with a histological proven (pre)malignancy had a smear classified as ‘suspicious'' or ‘uncertain''. Cytology classified 11 smears as ‘non-suspicious'', of which 10 (91%) were indeed normal skin or LS. The accuracy, based on the presence of a lesion, for (pre)malignant lesions with the use of the brush showed a sensitivity of 97% and a negative predictive value of 88%.

Conclusion:

Vulvar brush cytology is feasible and may be a first step in the development of a triage instrument to determine whether subsequent biopsy of a clinically (pre)malignant lesion is necessary.     

Minichromosome maintenance 7 protein is a reliable biological marker for human cervical progressive disease

Objective

This study focused on comparing the expression levels of p16, Ki-67, and minichromosome maintenance 7 (MCM7) protein in normal and affected cervical epithelium to ascertain the biological significance of these markers in detecting progressive cervical disease.

Methods

A quantitative and based on-scanning-microscopy analysis of the three markers expression was performed in normal and cervical intraepithelial neoplasia (CIN) I, II, and III tissues. p16 area as well as p16, Ki-67, and MCM7 positive cells or nuclei were evaluated according to their distribution and extent through the cervical epithelium.

Results

A clear p16 over-expression was observed in all the dysplastic epithelium tissue samples. The quantitative analysis of p16 area as well as the number of p16 positive cells was able to better discriminate the CIN lesions grades than the usual semi-quantitative analysis. The average Ki-67 labeling indexes for the normal epithelium, CIN I, CIN II, and CIN III groups were 19.8%, 27.3%, 32.8%, and 37.1%, respectively, whereas the mean MCM7 labeling indexes for the correspondent grades were 27.0%, 30.4%, 50.5%, and 67.2%. The Ki-67 and MCM7 labeling indexes were closely correlated with the CIN histological grade, with higher labeling indexe values obtained from the more severe lesions (p<0.05), being the MCM7 labeling indexes the highest values in all the CIN categories (p<0.05).

Conclusion

We observed a good correlation among the p16, Ki-67, and MCM7 data. In addition, MCM7 demonstrated to be a more efficient and sensitive marker to assess disease progression in the uterine cervix.     

Role of high risk-human papilloma virus test in the follow-up of patients who underwent conization of the cervix for cervical intraepithelial neoplasia

Objective

To examine whether the presence of high risk-human papilloma virus (HR-HPV) after conization of the cervix was a risk factor for persistence or recurrence of cervical intraepithelial neoplasia (CIN) and whether HR-HPV test could be a guideline for post-therapy surveillance.

Methods

The study retrospectively analyzed data from 243 patients who underwent LLETZ or CKC of the cervix due to CIN.

Results

A positive HR-HPV test result which was performed between 3 and 6 months after procedure was a risk factor for persistent or recurrent cytological (p<0.001, odds ratio [OR]=22.51, 95% confidence interval [CI]=9.74-52.02) and pathological (p<0.001, OR=18.28, 95% CI=5.55-60.20) abnormalities.

Conclusion

HR-HPV positive patients between 3 and 6 months after procedure should undergo frequent and meticulous post-therapy surveillance, while HR-HPV negative patients do not require such high-level surveillance and could undergo routine surveillance.     

A human papillomavirus (HPV)-16 or HPV-18 genotype is a reliable predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia 3

Objective

This study was conducted using the human papillomavirus (HPV) DNA chip test (HDC), in order to determine whether the HPV genotype is a predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3.

Methods

Between January 2002 and February 2015, a total of 189 patients who underwent a hysterectomy within 6 months of LEEP caused by CIN 3 were included in this study. We analyzed their epidemiological data, pathological parameters, high-risk HPV (HR-HPV) load as measured by the hybrid capture II assay, and HR-HPV genotype as measured by the HDC. A logistic regression model was used to analyze the relationship between covariates and the probability of residual disease in subsequent hysterectomy specimens.

Results

Of the 189 patients, 92 (48.7%) had residual disease in the hysterectomy specimen, CIN 2 in seven patients, CIN 3 in 79 patients, IA1 cancer in five patients, and IA2 cancer in one patient. Using multivariate analysis, the results were as follows: cone margin positivity (odds ratio [OR], 2.43; 95% CI, 1.18 to 5.29; p<0.05), HPV viral load ≥220 relative light unit (OR, 2.98; 95% CI, 1.38 to 6.43; p<0.01), positive endocervical cytology (OR, 8.97; 95% CI, 3.81 to 21.13; p<0.001), and HPV-16 or HPV-18 positivity (OR, 9.07; 95% CI, 3.86 to 21.30; p<0.001).

Conclusion

The HPV-16 or HPV-18 genotype is a reliable predictive factor of residual disease in a subsequent hysterectomy following a LEEP for CIN 3.     

Single and multiple high-risk and low-risk Human Papillomavirus association with cervical lesions of 11,224 women in Jakarta

Purpose

We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions.

Methods

Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped.

Results

Overall HPV prevalence was 10.7 %, and young women (under 21 years old) harbored highest HPV infection rate (40.38 %). The rate declined in old women 9.49 % (age 30–49) and 6.89 % (age 50 and above). Normal cytology had lowest HPV (5.66 %) compared to low-grade (60.49 %), high-grade (71.96 %) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9 %). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54 %) and HSIL (2.12 vs. 51.32 %). Multiple HPV infection was more frequent in young women under 30 years old (10 %) than older women (2 %) and in LSIL (20.2 %), HSIL (18.5 %) than SCC (4.4 %). HR HPV 52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2, 1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC.

Conclusion

Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies in Indonesia.

     

Zervixkarzinom und seine Vorstufen

Background

The nomenclature of squamous and glandular precursor lesions has been reformed in the World Health Organization (WHO) classification as well as in national and international guidelines in recent years.

Methods

This study was based on a PubMed search and a review of current national and international guidelines pertaining to the subject.

Results

With regards to cervical intraepithelial neoplasia associated with human papillomavirus (HPV), an accurate distinction between low grade and high grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and a thorough evaluation of glandular precursor lesions are emphasized. Morphological changes associated with the productive phase of HPV infection are referred to as LSIL and changes associated with deregulation of HPV expression and of the cell cycle as HSIL; however, for the clinical management of squamous cell precursor lesions, the 3?tiered classification of cervical intraepithelial neoplasia (CIN) is still indispensable. In the differential diagnosis of HPV-associated precursors and metaplastic squamous cell and glandular lesions in particular, the relevance of p16 immunohistochemistry or combined p16/Ki-67 determination is emphasized. The staging of cervical cancer has been complemented by subdividing stage IIA into IIA1 and IIA2 and the importance of a standardized determination of morphological prognostic factors is underlined. Particular attention must be paid to differentiate special types of squamous cell carcinoma and rare non-HPV associated adenocarcinomas.

Conclusion

The recently updated recommendations and guidelines on the diagnosis and classification of cervical cancer have taken our improved understanding of the biology and natural history of the disease into account.

     

Early human papillomavirus testing predicts residual/recurrent disease after LEEP

Objective

The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse.

Methods

We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse.

Results

Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months.

Conclusion

Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.     

Pregnancy outcome after cervical conization: risk factors for preterm delivery and the efficacy of prophylactic cerclage

Objective

This study examined the risk factors for preterm birth and the efficacy of prophylactic cerclage in patients who had undergone cervical conization due to cervical intraepithelial neoplasia before pregnancy.

Methods

We reviewed the medical records of all patients who gave live singleton births between May 1996 and April 2009, after having cervical conization. Delivery before 37 gestational weeks was considered as preterm birth. The pregnancy outcomes were analyzed with independent sample t-test, chi-square test, and multiple logistic regression using the SPSS ver. 12.0.

Results

Sixty five cases were found. The mean gestational age at delivery was 37 weeks (SD, 3.5). Eighteen patients (27.7%) had preterm delivery. The type of conization, the volume of the specimen, and second trimester cervical length were related to preterm birth (p≤0.001, p=0.019, p≤0.001, respectively). In multivariate analysis, only mid-trimester cervical length was statistically significant for preterm birth (p=0.012; odds ratio, 0.194; confidence interval, 0.055 to 0.693). Six out of 65 patients had undergone prophylactic cerclage, and three (50%) of them had preterm births, while 15 (25%) patients without cerclage had preterm births.

Conclusion

The type of conization, the volume of specimen, and second trimester cervical length may be the risk factors for preterm birth in patients who have a prior history of cervical conization. Prophylactic cerclage may not be helpful in preventing preterm birth, therefore more careful consideration should be paid in deciding cerclage after conization during prenatal counseling.     

Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media

Objective

To validate the efficacy of Seeplex HPV4A ACE for the detection of high-risk (HR) human papillomavirus (HPV) and HPV 16 and/or HPV 18 genotypes as compared to the PCR method and the Cervista HPV assays in cervical swab samples.

Methods

Besides liquid-based cytology, additional 97 cervical swab samples were collected for HPV genotyping by HPV4A ACE, Cervista HPV assays, and PCR method. To check the statistical differences, we also conducted the paired proportion test, Cohen''s κ statistic, and a receiver operating characteristic curve.

Results

Seeplex HPV4A ACE and the Cervista HPV HR showed substantial agreement with PCR for detection of HR HPVs (88.3%, κ=0.767 and 81.7%, κ=0.636, respectively). Seeplex HPV4A ACE also showed substantial agreement with the Cervista HPV 16/18 test (89.5%, κ=0.628). Additionally, the sensitivity and specificity of Seeplex HPV4A ACE and Cervista HPV HR were 91.4% vs. 84.5% and 73.4%, vs. 72.7%, respectively, when those higher than low-grade squamous intraepithelial lesions were regarded as abnormalities. HPV genotyping for HPV 16/18 detected cervical intraepithelial neoplasias (CINs) better than HR HPV tests (66.7% vs. 24.6% by HPV4A ACE, 52.6% vs. 25.9% by Cervista HPV assays in CIN II or more, relatively).

Conclusion

Seeplex HPV4A ACE is an effective method as the PCR and the Cervista HPV assays for the detection of HR HPVs and for genotyping of HPV 16 and 18.