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Diagnosis of a primary vaginal cancer is rare, as most vaginal tumors are metastatic from another primary site. Although cancer of the vagina is more common in postmenopausal women, an increase in young women being diagnosed with primary vaginal cancer has been reported, especially in countries with a high HIV prevalence. This is associated with persistence of high-risk HPV infection. The emphasis should be on primary prevention with prophylactic HPV vaccination. Once there is a suspicion of a primary vaginal cancer, this should be confirmed histologically with biopsy. Staging has been done clinically, as with cervical cancer; however, there is a role for imaging in assisting with staging as this is often a difficult assessment. Treatment should be individualized and depends on stage as well as histologic subtype. It is prudent to refer cases to centers of excellence with experience in dealing with this rare gynecological cancer.

Introduction: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. Material and methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. Results: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%–100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. Conclusions: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.

Vulvar and vaginal cancers are relatively rare cancers, together responsible for less than 1% of the global cancer incidence among women in 2018. The majority of vaginal cancers and a lesser proportion of vulvar cancers are associated with HPV, with rising incidence rates of vulvar cancer observed in younger women, possibly due to an increased prevalence of high-risk HPV types. This report assesses recent international variations in the incidence rates of vulvar and vaginal cancer derived from high-quality data from population-based cancer registries in 68 countries, and further assesses time trends for selected longer-term series in eight countries (Australia, China, Colombia, India, Norway, Slovakia, the U.S., and the U.K.) over the period 1983 to 2012. We observed a 30-fold variation in the recorded incidence rates of vulvar cancer in contrast with the threefold variation for vaginal cancer. We also observed a rising incidence of vulvar cancer in Australia, Norway and the U.K., and Slovakia, with a more rapid rise in the rates seen in women aged < 60 years at diagnosis. The annual percentage change over the most recent decade varied from 1.7% in Norway to 4.1% in Slovakia. The increases are largely confined to younger women and are likely linked to generational changes in sexual behaviour (earlier age at sexual debut and increasing transmission of HPV among cohorts born 1940 to 1950 and thereafter. Vaginal cancer incidence rates, in contrast, were lower and more stable, despite the higher HPV-attributable fraction relative to vulvar cancer. Irrespective of the trends, an increasing number of women are predicted to be diagnosed worldwide with both cancer types in future decades as population ageing and growth continues. The promise of high-coverage HPV vaccination will likely counter this rising burden, but the impact may take a number of decades.

Aim We report clinical outcomes of transarterial embolization in 19 cases of vaginal cancer. Methods From August 2011 to October 2019, 19 patients with histologically diagnosed vaginal cancer were identified in our department. Transarterial chemotherapy and embolization was performed for all patients. Patient characteristics, treatment plans and the clinical outcomes, were recorded. Results Among 19 identified cases, nine of them are squamous cell carcinoma, five of adenocarcinoma, one of adenosquamous carcinoma, two of vaginal malignant melanoma, one leiomyosarcoma and one of stromal sarcoma. Transarterial chemotherapy and embolization was successfully performed in all patients. No related complication was found after intervention treatment. Besides, eight patients received adjuvant chemotherapy, four received both adjuvant chemotherapy and radiotherapy and seven received no therapies. Four patients were cured and seven were stable during follow-up. Conclusion Transarterial embolization appears safe and effective for vaginal cancer, with a currently acceptable prognosis.

Objective To study the risk of vaginal cancer among hysterectomised women with and without cervical intraepithelial neoplasia (CIN). Design Population-based national cohort study. Setting and population All Swedish women, 5 million in total, aged 20 and up, 1987-2011 using national registries. Methods The study cohort was subdivided into four exposure groups: hysterectomised with no previous history of CIN3 and without prevalent CIN at hysterectomy; hysterectomised with a history of CIN3/adenocarcinoma in situ (AIS); hysterectomised with prevalent CIN at hysterectomy; non-hysterectomised. Main outcome measure Vaginal cancer. Results We identified 898 incident cases of vaginal cancer. Women with prevalent CIN at hysterectomy and those with a history of CIN3/AIS had incidence rates (IR) of vaginal cancer of 51.3 (95% CI 34.4-76.5) and 17.1 (95% CI 12.5-23.4) per 100 000, respectively. Age-adjusted IR-ratios (IRRs) compared with hysterectomised women with benign cervical history were 21.0 (95% CI 13.4-32.9) and 5.81 (95% CI 4.00-8.43), respectively. IR for non-hysterectomised women was 0.87 (95% CI 0.81-0.93) and IRR was 0.37 (95% CI 0.30-0.46). In hysterectomised women with prevalent CIN, the IR remained high after 15 years of follow up: 65.7 (95% CI 21.2-203.6). Conclusions Our findings suggest that hysterectomised women with prevalent CIN at surgery should be offered surveillance. Hysterectomised women without the studied risk factors have a more than doubled risk of contracting vaginal cancer compared with non-hysterectomised women in the general population. Still, the incidence rate does not justify screening. Tweetable abstract High risk of contracting vaginal cancer among hysterectomised women having prevalent CIN at surgery.

BACKGROUND Human papillomavirus (HPV) vaccines can potentially prevent greater than 90% of cervical and anal cancers as well as a substantial proportion of vulvar, vaginal, penile, and oropharyngeal cancers caused by certain HPV types. Because more than 38,000 HPV-associated cancers are diagnosed annually in the United States, current studies are needed to understand how relative survival varies for each of these cancers by certain demographic characteristics, such as race and age. METHODS The authors examined high-quality data from 27 population-based cancer registries covering approximately 59% of the US population. The analyses were limited to invasive cancers that were diagnosed during 2001 through 2011 and followed through 2011 and met specified histologic criteria for HPV-associated cancers. Five-year relative survival was calculated from diagnosis until death for these cancers by age, race, and sex. RESULTS The 5-year age-standardized relative survival rate was 64.2% for cervical carcinomas, 52.8% for vaginal squamous cell carcinomas (SCCs), 66% for vulvar SCCs, 47.4% for penile SCCs, 65.9% for anal SCCs, 56.2% for rectal SCCs, and 51.2% for oropharyngeal SCCs. Five-year relative survival was consistently higher among white patients compared with black patients for all HPV-associated cancers across all age groups; the greatest differences by race were observed for oropharyngeal SCCs among those aged

A custom balloon applicator was created to deliver intracavitary high‐dose‐rate brachytherapy to a patient with a superficial vaginal cancer. The patient was unable to be treated conventionally due to an extremely narrow introitus that prevented the introduction of a conventional cylinder applicator. The custom applicator was constructed by inserting a straight titanium tandem applicator through the drainage lumen of a Foley catheter. The applicator was inserted and the catheter balloon was inflated when positioned at the vaginal apex. Three brachytherapy treatments were performed using this technique. Individual balloon eccentricities resulted in small radial tandem offsets within the balloon. This phenomenon was exploited by orientating the tandem offset in the direction of the target volume. Acceptable dosimetry was achieved for all fractions and the procedure was very well tolerated. The custom applicator was a viable solution that was safely developed in a short time frame using equipment readily available in our department.

Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population-based Finnish Cancer Registry data to further study this connection. We identified all women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates. During the follow-up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05–1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9–38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01–9.44). The risk of cancers of the uterine cervix and lung was significantly decreased. LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.

Gel sonovaginography is a new way of assessing local cervical and vaginal disorders, in which regular transvaginal sonography is known to have limitations. In gel sonovaginography, 20 mL of ultrasound gel is instilled into the vagina, followed by examination with a transvaginal transducer. In a study involving 28 women with known or suspected disorders such as cervical and vaginal cancer, cervical polyps, vaginal septa, and deep infiltrating endometriosis, a substantial improvement in visualization and assessment of local lesions and structures was noted with gel sonovaginography. This simple technique appears to be valuable for accurate diagnosis of local cervical and vaginal disorders.

Primary cancer of the vagina is a rare entity, comprising only 1-2% of all gynecologic malignancies. Infection of human papillomavirus, immunocompromised condition, and chronic irritation of the vagina by prolonged pessary usage are known to contribute to the development of vaginal cancer. We experienced a rare case of vaginal cancer that occurred after usage of a vaginal pessary while the patient was prescribed with oral prednisolone for idiopathic interstitial pneumonia. Previous reports of vaginal cancer that occurred after pessary usage are mostly neglected pessaries, but in this case the patient was managed properly. We suspect that her immunocompromised condition, as well as her pessary usage, may have accelerated the development of vaginal cancer. The presence of multiple risk factors could be related to the pathogenesis of vaginal cancer, and therefore proper management is required after pessary insertion for uterine prolapse treatment.

A sarcoid-like reaction is a development of non-caseating granuloma in patients with underlying malignancy and represents a false positive finding on positron emission tomography/computed tomography (PET/CT). A sarcoid-like reaction is a benign condition; therefore, differentiating a sarcoid-like reaction from cancer recurrence is necessary. Only uterine and ovarian cancer related cases have been reported in the gynecological field and to the best of our knowledge, this is the first case of a sarcoid-like reaction in vaginal cancer. A 59-year-old vaginal cancer patient received concurrent chemoradiotherapy and achieved complete remission. Recurrence of vaginal cancer was suspected because of the elevation of serum squamous cell carcinoma antigen level. PET/CT revealed abnormal uptake at the bilateral mediastinal and hilar lymph nodes. A non-caseating granuloma was detected from the biopsy of the swollen lymph nodes. No evidence of cancer recurrence was observed. A sarcoid-like reaction should be considered when evaluating PET/CT in cancer patients to prevent unnecessary treatments.

The study was undertaken to assess the utility of cervico-vaginal/vault cytology in the follow-up of women treated for cervical cancer and benign gynecological conditions. Records of 3,523 cervico-vaginal smears from 2,658 women who underwent hysterectomy and/or radiotherapy or chemotherapy, over a 10-year period were retrieved. Data was collected on type of treatment received, indication for hysterectomy, age of patient, presenting symptoms, stage of tumor, interval since treatment, cytology and biopsy results. The results of cytology versus other parameters were analyzed separately for women treated for cervical cancer and those hysterectomized for benign indications. Malignant cells were detected in 141/1949 (7.2%) follow-up smears from treated cervical cancer cases (140 recurrences and 1 VAIN). Around 92% of recurrences of cervical cancer were detected with in 2 years of follow-up and 75% of these women were symptomatic. Cytology first alerted the clinicians to a recurrence in a quarter of cases. On the other hand, VAIN was detected in 5/1079 (0.46%) vault smears from 997 women hysterectomized for benign gynecologic disease. All these women were asymptomatic and majority (80%) were detected in follow-up smears performed between 3 and 10 years. Vault cytology is an accurate tool to detect local recurrences/VAIN in women treated for cervical cancer or benign gynecological conditions. It may even first alert the clinicians to a possibility of recurrence. However, due to extremely low prevalence of VAIN/vaginal cancer, it seems unwarranted in women hysterectomized for benign indications, especially in resource constrained settings. Diagn. Cytopathol. 2013;41:762–766. © 2013 Wiley Periodicals, Inc.

Aim Chronic radiation proctitis is a long-term complication of radiation therapy for pelvic malignancy. The aim of this study was to compare the efficacy and safety of two treatment regimens, sucralfate or placebo, following argon plasma coagulation (APC) for chronic haemorrhagic radiation proctitis. Method A single-centre, randomized, placebo-controlled, double-blind study was performed on patients with haemorrhagic chronic radiation proctitis after irradiation for prostate, uterine, cervical, rectal or vaginal cancer. All patients received APC, and were then randomized to oral sucralfate (6 g twice a day) or placebo treatment for 4 weeks. APC was repeated every 8 weeks if necessary after the first session. Patients were graded clinically and endoscopically according to the Chutkan and Gilinski scales before and at 8 and 16 weeks after initial APC treatment (1.5–2 l/min, 25–40 W) and after 52 weeks (clinical only). Results Of 122 patients, 117 completed the entire protocol, with 57/60 in the sucralfate group and 60/62 in the placebo group. At baseline there were no significant differences between the sucralfate and placebo groups. At 1 year, a significant improvement in the clinical scale in both groups occurred compared with baseline. After 16 weeks, the median overall clinical severity scores fell from 4 to 2 points and the median bleeding score from 2 to 0 in both groups. Conclusion APC is safe and effective for the management of chronic radiation proctitis. Additional sucralfate treatment did not influence the clinical or endoscopic outcome.

Introduction: Having previously modelled the optimal proportion of uterine cervix and corpus cancers that should be treated with brachytherapy (BT), we aimed to complete the assessment of the role of BT for gynaecological cancers by estimating the optimal proportion of vaginal cancer cases that should be treated with BT, the optimal BT utilisation (BTU) rate for vaginal cancer. We compared this with actual vaginal BTU and assessed quality of BT for vaginal cancer by a Patterns-of-Care Study (POCS). Methods: Evidence-based guidelines were used to construct an optimal BTU decision tree for vaginal cancer. Searches of the epidemiological literature to ascertain the proportion of patients who fulfilled the criteria for BT were conducted. The robustness of the model was tested by sensitivity analyses and by peer review. A retrospective POCS of BT in New South Wales (NSW) for 2003 was conducted, and actual BTU for vaginal cancer was determined. Differences between optimal and actual BTU were assessed. Quality of BT for vaginal cancer was compared with published benchmarks. Results: The optimal vaginal cancer BTU rate was estimated to be 85% (range 81–87%). In NSW in 2003, actual vaginal cancer BTU was only 42% (95% confidence interval 22–62%). In NSW, only nine patients were treated, all with intra-vaginal cylinders, and two of four to lower than recommended doses. Conclusions: BT for vaginal cancers is underutilised in NSW compared with the proposed optimal models of care. BT quality may have been suboptimal and this may relate to the rarity of this disease.

Aim Radiation-induced haemorrhagic proctitis is not uncommon after radiotherapy for pelvic malignancy. Various treatments have been described. Recurrent bleeding and subsequent complications associated with treatment have been reported. Colonic irrigation has been used to treat defaecation disorders; however, it has not been used to treat radiation-induced proctitis. Method A pilot study was undertaken of 12 patients with haemorrhagic radiation proctitis after radiotherapy. Four patients had had cervical cancer, five had uterine cancer, one had prostatic cancer, one had vesical cancer and one had vaginal cancer. Daily self-administered colonic irrigation with tap water and a 1-week period of oral antibiotics (ciprofloxacin and metronidazole) were prescribed. Results The median dose of radiation given was 54 (50–70) Gy. The median interval from radiation to the development of haemorrhagic proctitis was 26 (8–44) months. The median duration of symptomatic rectal haemorrhage prior to treatment was 8 (1–48) months. There was a significant improvement in rectal bleeding after treatment with colonic irrigation and oral antibiotic administration, accompanied by an improvement in bowel frequency and urgency, and diarrhoea. There were no complications. The majority of the patients (11/12) were satisfied with the treatment. The five patients who had previously undergone formalin therapy preferred the treatment regimen used in this study. Conclusion The preliminary results of colonic irrigation and oral antibiotics indicate that this treatment is safe and effective for radiation-induced proctitis. Further study is warranted.

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J (2010) Histopathology57, 907–916 Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16INK4Aoverexpression and clinicopathological correlations Aim: To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance. Methods and results: All cases of SCCVa diagnosed over a 15-year period from two hospitals in Barcelona, Spain (n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed

Vaginal clear cell adenocarcinoma (CCA) is well known to be associated with prenatal diethylstilbestrol exposure. We present a vaginal CCA with congenital anomalies of the genitourinary tract without prenatal diethylstilbestrol exposure. A 54-year-old woman complained of a 3-month history of genital bleeding. The examination revealed CCA at the anterior vagina and congenital anomalies. An anterior pelvic exenteration was performed. Macroscopically, bicornuate uterus, vaginal septum and left ureteral agenesis were found. Microscopically, vaginal CCA coexisted with adenosis and both metanephric and mesonephric remnants. The vaginal CCA was supposed to derive from coexisting adenosis. The adenosis was also supposed to occur as a congenital basis, together with genitourinary tract anomalies. Relations between congenital anomalies of the genitourinary tract and vaginal adenocarcinoma were suspected, resultantly.

A cohort of 26,876 women with surgical treatment for cervical intraepithelial neoplasia (CIN) during 1986-2004 was identified from the national Hospital Discharge Register. This cohort was followed up until December 31, 2006 (mean 8.4 years) through the Finnish Cancer Registry for cancer incidence during 1987-2006. There were 572 cases of cancer which is slightly more than would be expected on the basis of the national average cancer incidence in Finland. The standardized incidence ratio (SIR) was 1.14 and 95% confidence interval (CI) was 1.05-1.24. There was a statistically significant excess of cancers of the vulva (SIR: 6.15, 95% CI: 3.18-10.7), vagina (SIR: 9.08, 95% CI: 2.95-21.2), cervical cancer (SIR: 1.69, 95% CI: 1.07-2.53) and precancerous high-grade lesion of the uterine cervix (SIR: 1.29, 95% CI: 1.10-1.50). The SIR for smoking-related cancers combined, excluding cervical cancer, was 1.45 (95% CI: 1.12-1.86). The differences in cancer risk between treatment modalities were minor. Delivery after the CIN surgery did not decrease the overall cancer risk. In conclusion, women previously treated for CIN have an increased long-term risk of cancers related to human papillomavirus (HPV) and smoking.

Background Quadrivalent human papillomavirus (HPV types 6/11/16/18) L1 VLP vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and external genital disease. Herein, we evaluated the impact of the quadrivalent HPV 6/11/16/18 L1 VLP vaccine on prevention of HPV-associated cervico-genital lesions in a broad population of sexually active European women. Methods Female subjects (N = 9265) aged 16-24 with four or fewer lifetime sexual partners were enrolled and randomized to quadrivalent HPV vaccine or placebo. Subjects underwent cervicovaginal sampling for HPV DNA detection. Papanicolaou testing and anti-HPV 6/11/16/18 serology testing was also performed. Results Vaccine efficacy against lesions representing immediate cervical cancer precursors (cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ) related to HPV 6/11/16/18 in the per-protocol population was 100.0%[95% confidence interval (95% CI), 89.8-100.0]. Efficacy against external genital lesions (vulvar or vaginal intraepithelial neoplasia, condyloma, vulvar or vaginal cancer) related to vaccine HPV types in the per-protocol European population was 99.0% (95% CI, 94.4-100.0). Conclusion These data demonstrate that quadrivalent HPV 6/11/16/18 vaccination programs in 16- to 24-year-old European women can be beneficial. NCT0009252, NCT00092534, NCT00092495. (Less)

Objective To evaluate the feasibility of laparoscopic vaginal reconstruction using an ileal segment in patients with vaginal atresia, male-female transsexual patients, or patients who had vaginal cancer. Methods A retrospective review of the records of 80 patients who underwent laparoscopic vaginoplasty between 2004 and 2007 at Beijing Anzhen Hospital, China. Results Nineteen (23.8%) patients underwent total laparoscopic vaginoplasty and 61 (76.3%) underwent laparoscope-assisted vaginoplasty. There were 64 (80.0%) primary operations and 16 (20.0%) secondary operations. All of the surgeries were completed successfully and no intraoperative complications occurred. Mean follow-up time was 14 months. Postoperatively, 5 women had vaginal stenosis, while 4 women had no sexual partner during the follow-up period which meant that they could not be assessed completely. The remaining 71 patients were satisfied with their sexual lives after surgery. Conclusion Vaginal reconstruction performed via total laparoscopic vaginoplasty or a laparoscope-assisted technique using an ileal segment has a high success rate for a functional vagina and patient satisfaction.

Background Vaginal vault smears are used to detect persisting neoplasia of the lower genital tract after hysterectomy. Recent data suggest both widespread use and uncertain evidence of their effectiveness. Objectives To identify and synthesise evidence on the use and effectiveness of vaginal vault smears and to assess the quality. Search strategy ‘vault smear’ OR ‘vaginal vault smear’ OR ‘cervical vault smear’ OR (‘Hysterectomy’) AND (‘Follow up’ OR ‘Smear’). Selection criteria Primary research, women who had a hysterectomy and were followed up by vault cytology. Data collection and analysis Systematic search (eight electronic databases), supplemented by contact with experts and review of bibliographies. Two independent reviewers determined eligibility/validity and extracted data concerning test performance characteristics. Quality was assessed according to the established criteria. Results Of 441 unique references, only 19 were suitable. Quality of studies varied considerably and few were of ‘high’ methodological quality. Studies were geographically diverse, and were published over more than 40 years in 16 journals. From the higher scoring papers, there were 11 659 hysterectomies [6546, benign; 76, cervical intraepithelial neoplasia (CIN) I/CIN II; 5037, CIN III]. Proportions of abnormal vault smears and abnormal biopsies during follow up increased with worsening histology at hysterectomy (P < 0.0001 and P= 0.0001). There was only one report of vaginal cancer subsequent to hysterectomy for CIN and insufficient data to allow for reliable meta-analysis. Conclusions Vault smears cause anxiety, consume resources and their value is largely unproven. Inconsistency of study design and limited methodological quality means that the value of vault smears could not be established. High-quality research is required to ensure that the guidelines are evidence based.

Vaccines to prevent infection with high-risk human papillomaviruses (HPV) will help protect women against cervical cancer, and some are likely to be available within the next year. One vaccine, a quadrivalent vaccine against HPV types 6, 11, 16 and 18 and known as Garadsil ©(Merck &Co., Inc), was approved by the Federal Drug Administration (FDA) for the prevention of cervical cancer, cervical cancer precursors and vulval and vaginal cancer precursors associated with HPV 16 and 18 in June 2006. In addition, the vaccine has been approved for the prevention of genital warts and low grade cervical lesions e.g. cervical intraepithelial neoplasia1. The main vaccines components are recombinant viral capsid proteins assembled into virus-like particles and alum-based adjuvants. If given before HPV infection, the vaccines, which induce HPV type-specific, virus-neutralizing antibodies, have proven safe and highly effective at preventing HPV infection and its clinical consequences, including high-grade cervical lesions. Their use should not immediately alter existing screening programs for cervical cancer, however. Because they incorporate only the 2 HPV types most commonly associated with cervical cancer (HPV-16 and HPV-18), they can only prevent about 70% of cervical cancers. Vaccines to treat existing HPV infection are under development but are unlikely to become clinically available in the near future.

Cervical cancer remains the commonest cancer among women in developing countries, affecting women at their peak of social and economic responsibility. In poor countries where access to diagnosis and treatment is extremely limited, most of the affected women present with late-stage disease. Many do not even have access to palliative care. Outcome in women treated for cervical cancer is strongly influenced by the stage of diagnosis. The main treatment modalities remain surgical removal for early-stage disease and chemoradiation for late-stage disease. Cancers of the vulva, vagina, penis, and anus are much less common than cervical cancer although, in most cases, they also are associated with human papillomavirus infection. Diagnosis and chief treatment modalities for cervical and these less common cancers are discussed.

The US Preventive Services Task Force (USPTF) has recommended that routine vaginal Pap (V-Pap) screening is unnecessary for women status-post (S/P) total hysterectomy (T-Hyst) for benign disease (Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1996. p 105-118). However, many US women continue to have V-Pap despite no risk for cervical cancer and minimal risk for primary vaginal cancer (JAMA 2004;291:2990). Herein, we report our experience with such patients. Computerized data of patients S/P T-Hyst for benign conditions over a 6-yr-period were retrospectively evaluated. Pap diagnoses of epithelial abnormalities (Ep Abnl), negative for intraepithelial lesion or malignancy with/without nonneoplastic findings (NILM-NN and NILM), were reviewed based on three age groups: group A, 18-44 yr; group B, 45-64 yr; and group C, > or =65 yr (JAMA 2004;291:2990). A control group was used.Of 1,860 T-Hyst 1,303 (70%) were for benign disease. Of these 581/1303 (44.5%) patients had 819 current V-Paps (range, 1-5; mean, 1.4). The 581 patients were group A, 288 (49.5%); group B, 272 (46.8%); and group C, 21 (3.6%). Overall, the 819 V-Paps showed Ep Abnl, 28 (3.4%); NILM-NN, 252 (30.7%); and NILM, 539 (65.8%). Of the 28 Ep Abnl, 19 (67.8%) were atypical squamous cells of undetermined significance (ASCUS), and 9 (32%) were low-grade vaginal intraepithelial lesions (LG-VAIN). The NILM-NN findings included organisms, atrophy, and endometriosis. On the basis of individual age groups, Ep Abnl were only seen in V-Paps of 7/288 (2%) of group A and 21/272 (8%) of group B patients. In 23 control patients, 7/71 (9.8%) current V-Paps showed Ep Abnl (ASCUS, 4 (57%); LG-VAIN, 3 (43%)). Continued V-Pap in women S/P T-Hyst for benign disease does not appear to be useful, particularly in those aged > or =65 yr.

Invasive cancer of the cervix after treatment for cervical intraepithelial neoplasia (CIN) is becoming more important, as screening reduces the incidence of invasive disease. The rate of invasive cervical or vaginal cancer following treatment for CIN in UK remains elevated for at least 8 years. The aim of our study was to determine from international data how long this rate remains elevated and whether the rate of invasive disease reflects the rate of posttreatment CIN. The aim was to determine why the rate of invasive disease does not fall. A search of Medline and a secondary search of cited references identified 1,848 articles referring to the success rate of the treatment of CIN. Only 26 cohorts from 25 articles met all the inclusion criteria. The policy in these was to perform at least annual smears. After the first year following treatment for CIN, the rate of invasive disease remained about 56 per 100,000 woman years until at least 20 years after treatment. This rate is approximately 2.8 times greater than expected. In contrast, the risk of posttreatment CIN declined steadily with time to about 190 per 100,000 women in the 10th year. Although the posttreatment rate of CIN falls with time, the rate of invasive disease remains static. It seems likely that this is due to diminishing compliance with follow-up. Women should be encouraged to persevere with annual smears for at least 10 years after their treatment as this may offer them the best chance of detecting recurrence at a treatable stage.

Cutaneous metastasis in vaginal cancer is an extremely rare event and no cases of cutaneous metastasis from primary vaginal adenocarcinoma have been found. We report the clinicopathologic features, including cytopathologic findings, of the first case of cutaneous metastasis to the anterior chest wall from a sporadic-type advanced primary vaginal adenocarcinoma. Our present case suggested that cytopathologic examination should be performed as soon as possible when a patient exhibits multiple subcutaneous nodules or a painful cutaneous ulcer during treatment of advanced gynecologic cancer.

Patients undergoing radiotherapy for advanced cervical and endometrial cancer bear a considerable risk of developing vaginal preneoplastic lesions. Radiotherapy itself has been considered to have a role in the pathogenesis of vaginal dysplasia, although human papillomavirus (HPV) involvement has also been suggested. A series of 88 patients who underwent hysterectomy and were irradiated for gynecological cancer, including 43 with postradiation vaginal dysplasia at colposcopy and 45 without vaginal lesions, were included in this study. Detection and genotyping of HPV DNA in vaginal scraping were carried out by a PCR-based method and compared with colposcopic and cytological findings and with other clinical and laboratory data. Forty-two (97.7%) colposcopy-positive subjects and 6 (13.3%) colposcopically-negative patients were PCR-positive for high-risk HPV DNA (P < 0.000001). Twenty-two out of the 43 patients with colposcopic lesions showed an abnormal Papanicolau (PAP) test. Cytologic examination was negative in all colposcopically negative women. Type 16 HPV DNA was more frequent in patients with high-grade squamous intraepithelial lesions and in patients treated with external radiotherapy, whereas other types of high-risk HPV were more common in patients with low-grade lesions and in those treated with brachytherapy. When considering colposcopy as the standard for diagnosing vaginal dysplasia, HPV DNA testing was more sensitive than the PAP test. However, the specificity of the PAP test was higher with no false-positive case. In conclusion, vaginal preneoplastic changes in women post-hysterectomy and receiving radiotherapy for cervical, endometrial, and vaginal cancer represent an HPV-related nosologic entity. Whereas colposcopic examination can detect these preneoplastic lesions, HPV genotyping is a sensitive, inexpensive, and noninvasive method that may complement colposcopy and the PAP test.

Purpose. Our aim was to compare the role of remote afterloaded high-dose-rate brachytherapy (HDRB) with traditional low-dose-rate brachytherapy (LDRB) for patients with invasive primary vaginal carcinoma.Methods. The study group comprised 190 patients with invasive carcinoma of the vagina. The patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. Eighty patients were treated with intracavitary high-dose rate iridium 192 brachytherapy with or without external beam therapy. These patients are compared with a historical group of 110 patients treated with intracavitary low-dose-rate radium 226 or cesium 137 brachytherapy with or without external beam therapy.Results. No significant differences were found for stages, tumor grade or location between the two groups. Crude 5-year survival for all patients was 41% in the former LDRB group, 81% in stage I and 43% in stage II. Overall actuarial 3-year survival and disease-specific survival rates for all pati...

DES is the most carefully scrutinized EDC and its history provides valuable insights into the current evaluation of less well-studied EDCs. This review summarizes the health effects of prenatal exposure to diethylstilbestrol (DES) and emphasizes the role of DES as the first endocrine disrupting chemical (EDC). Vaginal clear cell adenocarcinoma (CCAC), the most severe consequence of prenatal exposure to DES, affected only 0.1% of exposed females, while the far more prevalent teratogenic and reproductive effects of DES were only discovered when DES daughter were screened for CCAC. Initial studies, conducted before most DES daughters had tried to conceive, examined vaginal cancer and vaginal, cervical and uterine abnormalities. Subsequently, several controlled studies demonstrated the increased risk of adverse reproductive outcomes in DES daughters. While most DES daughters can eventually experience a live birth, this is less likely in women with genital tract abnormalities, in whom there is a two-thirds chance that each pregnancy will be unsuccessful. In DES sons, who have been far less studied, results suggest male reproductive toxicity, but are less consistent. The importance of dose and gestational age at initial exposure are discussed, and the implications of DES findings for the evaluation of risks from current EDCs emphasized.

Background To assess the use of wide local excision in the treatment of VAIN. Methods A retrospective review on 40 WLE procedures for VAIN. Results The mean age was 60 years. Thirty-six (90%) patients had previous treatment for genital tract cancer or pre-cancer. The median duration and blood loss during operation was 45 minutes and 50 mls respectively. Fifteen complications affected 11 patients. Only one of five patients with 'vaginal cancer' was diagnosed prior to WLE. Of the 35 patients treated for VAIN 3, 12 (34%) developed abnormal cytology during follow up three had residual VAIN 3, five had recurrent VAIN 3 and four had invasive cancer diagnosed. The remaining 23 (66%) patients were disease free at a median follow up of 44 months. Conclusions Ablative therapy for VAIN 3 is unsafe as occult invasive foci can be missed by biopsy. WLE is efficacious in treating high grade VAIN 3. Long term surveillance of the lower genital tract is needed to diagnose metachronous lesions.

Glassy cell carcinoma is a rare neoplasm that occurs most frequently in the uterine cervix. We describe the first reported case of glassy cell carcinoma arising in the vagina. A 77-year-old Japanese woman was admitted to our hospital for atypical genital bleeding. Gynecological examination revealed a macroscopic vaginal cancer of 1.5 cm in diameter located in the upper 1/3 of the vagina. The pathological diagnosis of the biopsied specimen was glassy cell carcinoma. She was successfully treated by conventional radiation therapy and chemotherapy under the diagnosis of stage I vaginal cancer (International Federation of Gynecologists and Obstetricians classification, 1986). The patient is alive, without evidence of recurrence, 21 months following the radiation therapy. Glassy cell carcinoma is classified as the most poorly differentiated form of adenosquamous carcinoma. The present case illustrates the potential for glassy cell carcinoma to arise in the Mullerian epithelium throughout the female genital tract.

BACKGROUND This study was conducted to determine practice patterns in the management of vaginal malignancy. METHODS The National Cancer Data Base (NCDB), a large central registry of hospital case data, was reviewed for the 10-year period 1985-1994 for patients registered with a primary diagnosis of vaginal cancer. Patients with a prior history of malignancy were excluded. RESULTS Between 1985-1994 4885 cases of vaginal cancer were submitted to NCDB. More than 90% were epithelial neoplasia with approximately 25% of these in situ lesions only. Squamous carcinoma was more common as the age of the patient progressed. Adenocarcinomas represented nearly all the carcinomas in the group of patients age < 20 years and were observed less frequently with advanced age. Relative survival at 5 years was stage-related: Stage 0: 96%; Stage I: 73%; Stage II: 58%; and Stages III-IV: 36%. Melanoma had an extremely poor prognosis with a 5-year survival rate of only 14%. A significant number of sarcomas occurred in children for whom chemotherapy played a major role in treatment. Chemotherapy was used less frequently in the older patients. Survival was better in the younger patients (90% vs. 30% in the older patients). CONCLUSIONS Although vaginal cancer is the rarest of genital malignancies, it appears that treatment and results from the NCDB reported from multiple institutions followed prescribed treatment guidelines. Cancer 1998;83:1033-1040. © 1998 American Cancer Society.

Aims: To document the clinical, morphological and immunohistochemical features of two cases of primary mucosal melanoma with osteocartilaginous differentiation. Materials and methods Two cases of mucosal melanoma with cartilage and bone formation are reported, one arising in the vagina of a 79-year-old woman and one in the oral cavity of a 67-year-old man. The vaginal melanoma exhibited only cartilaginous differentiation. The oral cavity mucosal melanoma exhibited both bone and cartilage formation and was remarkable for its multifocality, long history not associated with metastases and its lengthy manifestation of dual morphologies: some of the tumours were typical in situ/invasive melanotic melanomas whilst the others were composed of amelanotic spindle and epithelioid cells with osteocartilaginous tissue. One of the lesions exhibited in situ and invasive melanoma with transition to an osteogenic tumour in places. The patient also developed non-osteogenic malignant melanomas in the nasal cavity and nasopharynx. Conclusions Malignant melanomas showing foci of osteocartilaginous differentiation are extremely rare with only 18 cases reported. Primary mucosal malignant melanomas of vagina and oral cavity showing osteocartilaginous differentiation have not previously been documented. Primary vaginal melanoma with cartilaginous differentiation must be distinguished from primary malignant mixed Mullerian tumour whilst malignant change in a pleomorphic adenoma, sarcomatoid carcinoma, osteogenic sarcoma and mesenchymal chondrosarcoma are included in the differential diagnosis of primary oral mucosal melanomas with osteocartilaginous differentiation. In this context, immunohistochemistry using antibodies to cytokeratin, S100 protein and MIC2 is of value.

Purpose: To establish a workflow for NRG-GY006 IMRT pre-treatment reviews, incorporating advanced radiotherapy technologies being evaluated as part of the clinical trial. Methods: Pre-Treatment reviews are required for every IMRT case as part of NRG-GY006 (a randomized phase II trial of radiation therapy and cisplatin alone or in combination with intravenous triapine in women with newly diagnosed bulky stage I B2, stage II, IIIB, or IVA cancer of the uterine cervix or stage II-IVA vaginal cancer. The pretreatment review process includes structures review and generating an active bone marrow(ABM)- to be used as an avoidance structure during IMRT optimization- and evaluating initial IMRT plan quality using knowledgeengineering based planning (KBP). Institutions will initially submit their simulation CT scan, structures file and PET/CT to IROC QA center for generating ABM. The ABM will be returned to the institution for use in planning. Institutions will then submit an initial IMRT plan for review and will receive information back following implementation of a KBP algorithm, for use in re-optimization, before submitting the final IMRT used for treatment. Results: ABM structure is generated using MIM vista software (Version 6.5, MIM corporation, Inc.). Here, the planning CT and the diagnostic PET/CT are fused and a sub threshold structure is auto segmented above the mean value of the SUV of the bone marrow. The generated ABM were compared with those generated with other software system (e.g. Velocity, Varian) and Dice coefficient (reflects the overlap of structures) ranged between 80 – 90% was achieved. A KBP model was built in Varian Eclipse TPS using the RapidPlan KBP software to perform plan quality assurance. Conclusion: The workflow for IMRT pretreatment reviews has been established. It represents a major improvement of NRG Oncology clinical trial quality assurance and incorporates the latest radiotherapy technologies as part of NCI clinical trials. This project was supported by grants U24CA180803 (IROC), UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI) and PA CURE grant

The prognostic impact of FIGO stage, histology, histologic grade, age and race in survival for cancers of the female gynecological (cervix, endometrium, ovary, vulva, vagina) were examined using cases obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program that were diagnosed between 1973 and 1987. Utilizing Cox proportional hazards modeling and relative survival rates analysis of 17,119 cases of cervical cancer indicated that the International Federation of Gynecology and Obstetrics (FIGO) stage, histology, histological grade, lymph node status, and age at diagnosis were all independently prognostic. No evidence was found of survival differences between squamous cell carcinoma and adenocarcinoma. Younger women were not found to have a poorer prognosis, survival declined with increased age. Analysis of 41,120 cases of endometrial cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnostic, and race were all prognostic factors. Clear cell adenocarcinoma, leiomyosarcoma, and mixed mullerian tumors were all found to have poorer prognosis. Analysis of 21,240 cases of ovarian cancer indicated that FIGO stage, histology, histologic grade, lymph node status, age at diagnosis, presence of ascites, and race were all prognostically significant. Analysis of 2,575 cases of vulvar cancer indicated that FIGO stage, histology, histologic grade, age, and race were all prognostically significant. Analysis of 916 cases of vaginal cancer indicated that FIGO stage, histologic grade, lymph node status, and age are all prognostically significant. Additional analysis of the data by combinations of independent prognostic factors indicates that the interaction of factors may be more predictive of outcome than any one factor separately. © 1994 Wiley-Liss, Inc.1

From 1967 to 1990, 96 previously untreated patients with cervicovaginal cancer associated with a history of vaginal pessary use to control uterovaginal prolapse were referred to eight radiation therapy departments in France. Sixty-eight patients had cervical cancer, and 28 had vaginal cancer. The mean interval between pessary insertion and cancer diagnosis was 18 years, with a range of 1 to 41 years. Most patients received radiation therapy and brachytherapy. Few (5%) had Grade 3 treatment side effects. The overall 5-year relative survival rate was 54%; nonsurvival was related to locoregional recurrence. Because almost all tumors occurred at the site of pessary insertion, foreign body chronic inflammation in association with viral infection may be the cause of the tumors.

The incidence and nature of perioperative complications associated with gynecologic brachytherapy applications were determined in 462 implants performed on 327 patients with cervical, endometrial, or vaginal cancer from 1986 to 1988. Twenty-one patients (6.4%) had life-threatening complications, including cardiac (16 patients), thromboembolic (4 patients), and pulmonary (1 patient) events. Three complications (0.9%) were fatal within the first 30 days, and two patients died of delayed sequelae of perioperative complications; thus, there was an overall 1.5% mortality rate. Patients experiencing life-threatening complications tended to be older (P = 0.0002), and to have a history of cardiac disease (P = 0.0002) and an increased American Society of Anesthesiology (ASA) score (P = 0.003). Logistic analysis demonstrated that a history of cardiac disease and increased age were independent predictors of life-threatening complications (P = 0.01). Careful patient selection and intensive perioperative care of the high-risk patient may prove to substantially diminish these complications.

Leiomyoma developing de novo from fibromuscular elements of the vagina is rare. Management of large vaginal leiomyomas might present a significant surgical challenge due to their anatomical location and high vascularity. We report a rare case of a primary leiomyoma of anterior vaginal wall in a woman who had previously had a total abdominal hysterectomy for uterine fibroids. (excerpt)

Purpose: Toptimized dosimetry of a CT/MRI multi‐lumen brachytherapy applicator was planned to treat vaginal cancer after hysterectomy. Multichannel design of cylinder includes several peripheral channels isotropically placed 5mm inside cylinder from surface with a separate central channel to allow single lumen brachytherapy as an option. The optimized dosimetry plans were compared between single‐channel versus multi‐channel to determine the sufficient coverage to the vaginal apex and other potential dosimetric advantages. Methods: CT simulation for each treatment of vaginal brachytherapy of postoperative endometrial or vaginal cancer. Seventeen CT image data sets were collected in this study. Standard single channel treatment was planned. Prescribed dose was to the 5mm cuff from the cylinder surface. PTV of 5mm rind with prescribed length was constructed. Doses to PTV and ROIs such as bladder and rectum were documented in DVH. Dose point to the apex of 5mm rind which locates at 5mm from applicator tip was specified. A second brachytherapy plan was generated using a multi‐channel loading. DVH of 5mm rind coverage, doses to apex, bladder and rectum were optimized in Oncentra brachytherapy planning system. Results: Optimized 95% to V95 and lower dose to adjacent structures were reported in multi‐channel plan. Improvements to apex dose by 3‐5% and organ sparing by 7‐14% were achieved. At the apex, inverse planning was further optimized by adjusting unequal contribution selectively from multi‐channel end. It is difficult for single channel to eliminate the cold spot at apex and maintain the dose uniformity to the 5mm cuff simultaneously. Conclusion: Possible optimization of brachytherapy treatment planning of vagina is investigated in this study by using a new multi‐lumen vaginal cylinder. The new device can increase the therapeutic ratio by improving target coverage and at the apex region as well. A reduction in the potential toxicity to the adjacent critical organs is feasible.