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Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on H&E. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.

Purpose Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. Methods The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. Results A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities — benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. Conclusions Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.

The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results. Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively. External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%). The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Malignancies of the vagina are rare, but colposcopy-directed biopsies play a major role in detecting vaginal intraepithelial lesions. Data of accuracy in detecting neoplasia of the vagina are very rare compared to accuracy in detecting cervical neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with clinical findings of the examiner. The accuracy of colposcopy-directed biopsy was compared with the clinical finding in relation to the patient’s age and the examiner’s level of training. This was done in combination with PAP-smear, HPV-test results, and the history of other malignancies of the lower genital tract. The data were collected between January 2014 and February 2018 at the certified Dysplasia Unit of the University Hospital Erlangen. In total, 253 biopsies from 253 women from the vagina were obtained. The overall accuracy of biopsy in comparison with clinical finding was 52.17% for all entities—benign lesions, low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and vaginal carcinoma. The accuracy for detecting HSIL was 82.46% (47/57), with an underdiagnosis rate of 15.79% and an overdiagnosis rate of 1.79%. With a sensitivity of over 80%, colposcopy-directed biopsy plays an important role in detecting vaginal–HSIL. A highly experienced practitioner is increasing the sensitivity in detecting vaginal–HSIL. Careful examination is required in women with a history of HSIL of the lower genital tract or with simultaneous neoplasia because they are of greater risk of developing vaginal malignancies. The combination of careful clinical work up, PAP-smear, HPV-testing, and colposcopy-guided biopsy is crucial in detecting vaginal–HSIL.

Background and Objectives Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. Methods A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. Results Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P

Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient’s age, and the examiner’s level of training. The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities—benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma—with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ 1, TZ 2, or TZ 3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0–34), 83.6% (age 34–55), and 80% (age 55 or older). A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient’s age. The examiner’s level of training does not have any substantial influence on the accuracy.

To analyze reoperation rates and perioperative outcomes after long-term follow-up of two surgical approaches in the treatment of endometrial cancer when the standard of care shifts from open surgery to laparoscopy at a university hospital. In this retrospective monocenter study a total of 267 patients with endometrial cancer were included; 107 women underwent laparoscopy and 160 laparotomy. All of the patients received total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy, depending on individual pathological features (e.g. high risk for positive lymph nodes) and the expertise of the surgeon. Repeat surgery was needed significantly more often in the laparotomy group in comparison with the laparoscopy group (11.9 vs. 0.9 %, respectively; P

5592 Background: Currently, there are two major pathways for tumorigenesis of vulvar squamous cell carcinoma (VSCC) – an HPV-dependent with p16 overexpression as a surrogate for HPV-associated transformation and an HPV-independent route linked to lichen sclerosus, characterized by p53 mutation. A possible correlation of HPV dependency with a favourable prognosis has been proposed. Methods: The AGO CaRE-1 study is a retrospective survey of pts with primary VSCC FIGO stage ≥1B (UICC-TNM version 6) treated at 29 gynecologic cancer centers in Germany 1998-2008 (n = 1,618). For this CaRE-translational sub-study available FFPE tissue was collected centrally (n = 648). A tissue micro array (TMA) was constructed; p16 and p53 expression was determined by immunohistochemistry (IHC). HPV status and subtype were analyzed by PCR. Results: p16 IHC was interpretable in 550 TMA spots and considered positive in 166/550 (30.2%). HPV DNA was detected in 78.4% of the p16+ tumors, with HPV 16 being the most common subtype (88.3%) . Pts with p16+ tumors were younger at diagnosis (63 vs. 70 yrs for p16- tumors; p = 0 < 0.01) and showed lower rates of lymph-node involvement (29.0% vs. 39.7%; p = 0.021). p53 IHC was interpretable in 597 spots, 187/597 (31.3%) were considered positive. Pts with p53+ tumors were older at first diagnosis (71 vs. 66 yrs; p = 0.001 for p53- tumors) and showed lymph-node involvement more often (43.3% vs. 31.1%; p = 0.007). There was a relevant number of tumors with neither p16 nor p53 overexpression (221/535); while co-expression of p53 and p16 was rare (12/535). For survival analyses, three groups were defined: p53+ (n = 163), p16+/p53- (n = 151) and p16-/p53- (n = 221). 2-y-disease-free (DFS) and overall survival (OS) rates were significantly different between the groups: DFS: p53+ 47.0%; p16-/p53- 53% and p16+/p53- 65.5% (p < 0.001); OS: 70.4%, 72.6% and 82.7% (p = 0.003), respectively. Adjustment for age and nodal status showed consistent p16 and p53 effects regarding DFS. Conclusions: p16 overexpression is associated with an improved prognosis in VSCC while p53 positivity is linked to an adverse outcome. Our data provide evidence of a clinically relevant third subgroup of VSCC with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynakologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft fur Gynakologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

An incidental finding of atypical endometrial hyperplasia (AEH) in women who have undergone laparoscopic supracervical hysterectomy (LASH) is a rare phenomenon, and it is unclear whether laparoscopic extirpation of the cervical stump (LECS) is justified in these patients.LECS due to AEH found incidentally in the morcellated uterus after LASH.A total of 332 women underwent LASH between January 2002 and September 2010. Five of the women (1.5%) underwent secondary LECS procedures due to histological evidence of AEH or focal atypical endometrial cells found incidentally in the morcellated uterus. No atypical endometrial cells were histologically diagnosed in the cervical stump in any of the cases, nor were any endometrial cells found in the cervical stumps in any of the 5 patients. There was no abdominal evidence at all of any disseminated endometrial cells. In all 5 cases, cytological examination of peritoneal fluid confirmed the absence of adenocarcinoma cells.No signs of AEH were found in the removed cervical stumps. However, women should receive counseling regarding the need for secondary LECS to minimize any risks in such cases.

There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P

Background: Infections with high-risk human papillomavirus (HPV) types such as HPV-16 and HPV-18 are known to be major risk factors for the development of cervical cancer, whereas low-risk HPV types cause benign genital lesions. The effect of co-infections with low-risk HPV viruses and high-risk HPV types on the development of cervical cancer and cervical intraepithelial dysplasia (CIN) is less clear. We investigated the correlation of infections with high- and low-risk HPV types and their combination with different histologically verified grades of CIN. Methods: 1161 women who presented to the Colposcopy Clinic of our department were tested for low-risk and high-risk HPV types using the Hybrid Capture II assay. 427 of those women had a histologically verified CIN, their HPV status was correlated with the degree of cervical dysplasia. Results: CIN III was significantly correlated to a high-risk HPV infection (adjusted Odds ratio 11.725, 95%, Cl 7.119 - 19.330) compared to a combined infection with low-risk and high-risk types (OR 5.29, 95% CI 2.681-10.437) (Pearson Χ 2 p = 0.004), whereas no significant differences were seen for mild or moderate dysplasia. Conclusion: High-grade CIN is detected less often in women with concomitant infections of both low-risk and high-risk HPV types compared to women infected with high-risk HPV types only. Our results support the hypothesis of antagonistic effects for the development of cervical dysplasia in patients with combined low- and high-risk HPV infections.

Background. To study the rate of regression and progression into invasive disease of patients with histologically proven carcinoma in situ of the uterine cervix during pregnancy. Methods. Prospective observation of all pregnant women with biopsy-proven carcinoma in situ of the uterine cervix, gained by colposcopic guided biopsy from 1996 to 2004 and correlation with the route of delivery and cytologic and histologic postpartum findings. Results. Eighty-three patients with histologically verified carcinoma in situ during pregnancy were treated conservatively. Two patients were lost to follow-up, one patient had an abortion, and three are still pregnant. The study population of 77 patients were followed for a median of 140 days before delivery. Postpartum regression rate was 34.2%, two patients had a diagnosis of microinvasive cervical cancer on the postpartum cone biopsy, and persistent carcinoma in situ was found postpartum in 63.1% of patients. No difference was seen for the route of delivery. Both patients with microinvasive carcinoma were delivered by primary cesarean section and are disease-free after 24 and 38 months, respectively. Conclusions. We recommend conservative management for women with carcinoma in situ of the uterine cervix. We found no difference for the route of delivery regarding postpartum regression and recommend a postpartum evaluation after the puerperium. Colposcopic guided biopsy should rule out an invasive process during pregnancy. Cesarean section as the mode of delivery should be considered, if invasion is suspected.

The benefits of cytology-based cervical cancer screening programs in reducing morbidity and mortality are well recognized. Especially, overtreatment of human papillomavirus (HPV) high-risk positive early dysplastic lesions may have a negative impact on reproductive outcomes for fertile women. To optimize the clinical management an objective standard is needed to distinguish precancer that requires treatment, from spontaneously resolving HPV infections. In the current study, we examined the prognostic relevance of HPV-L1 capsid protein analysis with Cytoactiv in an international prospective multicenter study including 908 HPV high-risk positive early dysplastic lesions (LSIL/HSIL) during a follow-up period of 54 months. The clinical end points of the study were histologically confirmed CIN3+ as progression, CIN1/2 for stable disease and repeated negative Pap smears as spontaneous clinical remission. The difference of the clinical outcome of HPV-L1-negative and HPV-L1-positive cases was statistically highly significant (P-value

Objective The advantages of the various methods used for hysterectomy are currently a topic of debate, and there is particular controversy over whether the cervix should be left in situ or not. The aim of this study was to compare the prevalence of hypoactive sexual desire disorder (HSDD) after five different hysterectomy procedures. Study design The Brief Profile of Female Sexual Function (B-PFSF) score was measured to compare postoperative prevalence of HSDD after the different surgical procedures. The questionnaire was sent to 590 women who had undergone hysterectomy between 2002 and 2007 for benign conditions. The following procedures were performed: abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopy-assisted vaginal hysterectomy (LAVH), laparoscopic supracervical hysterectomy (LASH), and total laparoscopic hysterectomy (TLH). Results A total of 304 questionnaires returned and 258 were found to be eligible for analysis. The mean follow-up intervals were 2 years for women after LASH and TLH and 3 years for women after AH, VH, and LAVH. The women in the AH group were significantly older than those in the LASH group, and the women in the VH group were significantly older than those in the LASH or TLH groups. The median B-PFSF score was highest at 26 in women after LASH, 25 in women after TLH, 23 in women after LAVH, 23.5 in women after VH, and 21 in women after AH. There were no statistically significant differences between the groups. Conclusions No differences were observed using the B-PFSF score with regard to the prevalence of HSDD after hysterectomy, irrespective of the surgical technique used.

Purpose: Diagnosis of cervical intraepithelial neoplasia (CIN) is currently based on the histological result of an aiming biopsy. This preliminary study investigated whether diagnostics for CIN can potentially be improved using semiautomatic colposcopic image analysis. Methods: 198 women with unremarkable or abnormal smears underwent colposcopy examinations. 375 regions of interest (ROIs) were manually marked on digital screen shots of the streaming documentation, which we provided during our colposcopic examinations (39 normal findings, 41 CIN I, and 118 CIN II–III). These ROIs were classified into two groups (211 regions with normal findings and CIN I, and 164 regions with CIN II–III). We developed a prototypical computer-assisted diagnostic (CAD) device based on image-processing methods to automatically characterize the color, texture, and granulation of the ROIs. Results: Using n-fold cross-validation, the CAD system achieved a maximum diagnostic accuracy of 80% (sensitivity 85% and specificity 75%) corresponding to a correct assignment of abnormal or unremarkable findings. Conclusions: The CAD system may be able to play a supportive role in the further diagnosis of CIN, potentially paving the way for new and enhanced developments in colposcopy-based diagnosis.

Die Diagnostik der zervikalen intraepithelialen Neoplasien (CIN) der Cervix uteri stützt sich derzeit auf die Zytologie, dem individuellen Erfahrungsschatz des Untersuchers in der Kolposkopie und letztlich auf die histologische Diagnostik. Ein von uns prototypisch entwickeltes System der Computer-assistierten Diagnose für die Kolposkopie erzielt bei einer automatischen Analyse von Bildbefunden eine höhere Sicherheit gegenüber der gängigen Diagnostik der Kolposkopie von 80 % (Sensitivität: 85 %, Spezifität: 75 %). Untersucht wurde in dieser Pilotstudie die Fragestellung ob ein solches CAD-System prinzipiell die Beurteilung des Untersuchers positiv unterstützen und damit die Gesamtdiagnostik verbessern kann. Im Rahmen einer Observerstudie wurden 24 digitalisierte kolposkopische Aufnahmen von Patientinnen der Dysplasiesprechstunde durch 21 Studienteilnehmer beurteilt. Unter den Studienteilnehmern waren 8 Experten mit einer kolposkopischen Erfahrung von mehr als 4 Jahren sowie 13 Nicht-Experten mit einer Erfahrung unter 4 Jahren. Alle Studienteilnehmer hatten im Rahmen eines Kolposkopiekurses die gleichen Grundlagen erworben bzw. aufgefrischt. Es wurde eine organisierte Beurteilung der Bilder ohne und mit in Anspruchnahme des CAD-Prototypen durchgeführt. Es zeigte sich eine höhere Varianz bei den Nicht-Experten im Gegensatz zu den Experten. Die Sicherheit bei der Befundung der Bilder zeigt eine Gesamtverbesserung nach Inanspruchnahme des CAD-Systems (Nicht-Experten: mittlere Sensitivität von 76 % auf 82 %, mittlere Spezifität von 62 % auf 65 %, Experten: mittlere Sensitivität von 73 % auf 79 %, mittlere Spezifität: 69 %). 85 % der Teilnehmer empfanden durch die Benutzung des CAD-System eine höhere Befundungssicherheit. 76 % der Teilnehmer meinten die Befundung schneller durchführen zu können. Das untersuchte CAD-System besitzt in seiner derzeitigen Entwicklungsstufe eine unterstützende Funktion in der weiterführenden Diagnostik der zervikalen intraepithelialen Neoplasien (CIN) und könnte potenziell zur Verbesserung der Befundung beitragen.

Objective To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis , are associated with endometriosis lesions. Design Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction–based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. Setting University hospital. Patient(s) Seventy individual patients with and without endometriosis. Intervention(s) Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. Result(s) Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. Conclusion(s) HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.

Background Persistent infection with high-risk human papilloma virus (HPV) is a prerequisite for the development of cervical cancer. The prognostic value of HPV-16 capsid antibodies in patients with invasive cervical cancer and its correlation with clinicopathological factors were investigated. Patients and methods Serum samples from 150 patients with invasive cervical cancer and 40 healthy female control subjects were analyzed by ELISA for HPV-specific antibodies to HPV-16 L1 virus-like particles (VLPs). Results HPV-16 L1 antibodies were detectable in 65 out of 150 patients (43.3%) and in 12 out of 40 controls (30.0%). Seropositivity was correlated with prolonged, progression-free (p =0.012) and overall survival (p=0.043). Especially in the early FIGO-stages I and II antibodies to HPV-16 L1, VLPs predicted a better outcome. Conclusion Antibodies to HPV-16 L1 capsid protein may be of prognostic value for patients with invasive cervical cancer and lack of HPV-16 L1 antibodies may indicate a group of patients with a poor prognosis.

Objective To investigate whether it is possible to use detection of the human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). Study design Pap smears from 279 women in whom CIN 1 and CIN 2 had been diagnosed by cytology and histology, who were known to have a high-risk HPV status and had a median follow-up of 25 months, were immunohistochemically stained for the HPV L1 protein. The staining results were correlated with the clinical course of the disease. Results HPV L1-positive patients showed regression in 49.1% of cases, stable disease in 41.5%, and progressive disease in 9.4%, whereas HPV L1-negative women had progression in 25.9% of cases (regression 33.3%, stable disease 40.7%; p = 0.001). The effect was clearest in the group under 30 years of age. HPV L1-negative patients experienced progression significantly more often than women with a positive HPV L1 test (odds ratio 3.391). Conclusions HPV L1-positivity was found to have prognostic significance in relation to disease progression in women with CIN 1 and CIN 2 and particularly in those less than 30 years of age.

Invasive cervical cancer is the most common form of malignancy in pregnant women. The incidence of carcinoma in situ-generally detected through an abnormal Pap smear-is increasing along with the median reproductive age in women who reside in industrialized countries. The threat that CIS will progress to invasive cervical cancer is a particular concern in relatively older women. In an effort to clarify the problem of whether cone biopsy should be done during pregnancy, the course of disease was followed prospectively in 83 pregnant women seen in the years 1996-2004 in whom a colposcopic-guided punch biopsy of the cervix disclosed squamous-cell CIS. The state of the cervix was estimated every 8 weeks by a Pap smear and colposcopy up to 36 weeks' gestation, and again 6 to 8 weeks after delivery. About 40% of affected women were seen in the first trimester, 41% in the second, and the rest in the third trimester. Of 68 women evaluated before pregnancy, 25 had low-grade, and 5 high-grade lesions. In more than 90% of cases, the colposcopic impression of CIS correlated with the biopsy findings. A total of 77 patients were followed up for a median of 140 days before delivery. The rate of postpartum regression was 34%. Two patients received a diagnosis of microinvasive cervical cancer from the findings at postpartum cone biopsy. CIS persisted in 63% of cases. The course of CIS did not depend on the route of delivery. Both patients with microinvasive carcinoma had primary cesarean delivery, and were free of disease when evaluated after 24 and 38 months, respectively. Eight women followed up for a median of 38 months again had suspect Pap smear findings, and all of them remained high-risk positive for human papillomavirus (HPV). These findings support a policy of observation for women in whom cervical CIS is found during pregnancy. HPV testing may be helpful for detecting recurrent dysplasia. A negative colposcopic-guided biopsy should exclude invasive disease. If invasion is suspected, operative delivery should be considered.