Tools
Vaginal Cancer
Introduction
Primary vaginal cancer is rare, comprising 1-2% of all female reproductive tract cancers.[1] The vagina is a 7 to 10-centimeter-long fibromuscular tube extending from the cervix to the vulva, sitting posterior to the urethra and bladder and anterior to the rectum. It is divided into 3 parts, essential for classifying tumor location and lymphatic drainage. The lower third is below the level of the bladder base with the urethra anteriorly, the middle third is adjacent to the bladder base, and the upper third is at the level of the vaginal fornices, denoted as anterior, posterior and lateral to the cervix.[2] Primary vaginal cancer is strictly defined as a disease without evidence of cervical or vulvar cancer or a history of either within the past 5 years. Most vaginal lesions (80-90%) originate from cervical or vulvar lesions or other local sites such as the endometrium, bladder, rectosigmoid, or ovary. Distant sites of metastasis include the colon, breast, and pancreas. When primary vaginal cancer is suspected, a biopsy is done for histopathologic confirmation.[1][3] While current estimates of vaginal cancer are higher than vulvar cancer, these estimates include primary and other genital lesions.[4] Currently, there are no randomized trials for the treatment of vaginal cancers due to the rarity of the disease, and guidelines are generally based on limited studies.[5]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
The pathways of carcinogenesis for vaginal cancer can be divided into human papillomavirus (HPV) induced and non-HPV induced.[6] As with cervical cancer, the HPV 16 virus strain accounts for most HPV-positive patients.[7] Within the HPV DNA, the activity of the viral reading frames E6 and E7 create proteins that interfere with critical cell cycle points. E6 interferes with suppressive tumor protein p53 and E7 with retinoblastoma protein. These are significant factors in HPV-related neoplasia, including primary vaginal cancer. The E5 protein may also play a role in immune evasion.[8] Historically, diethylstilbestrol, a synthetic estrogen used to prevent miscarriages and preterm labor, has been associated with vaginal clear cell adenocarcinoma in offspring.[9] The incidence of this cancer has decreased since the routine use of diethylstilbestrol was discontinued in the 1970s.
Epidemiology
Squamous cell carcinoma (SCC) of the vagina accounts for 90% of all patients with primary vaginal cancer, followed by adenocarcinoma, clear cell adenocarcinoma, melanoma, sarcoma, and lymphoma of the vagina.[5] Invasive vaginal cancer shares many risk factors with cervical cancer, such as tobacco use, younger age at first intercourse, HPV infection, and multiple sexual partners.[10] The incidence of vaginal cancer arising primarily from the vagina increases with age, with approximately 50% of patients presenting over the age of 70 years and 20% over 80 years.[11] Of these cancers, SCC is by far the most common.[12] The average age of diagnosis is 67 years. Approximately 15% of women are diagnosed under age 50; these are usually associated with cervical cancer.[5] Vaginal melanomas most likely originate from mucosal melanocytes and most commonly present as vaginal bleeding in White women with a mean age of 60 years.[13] Verrucous carcinoma is a low-grade malignant variant of SCC and presents as a large warty-appearing mass. This variant can be aggressive locally but is rarely metastatic.[14] While other sarcomas can arise in the vagina, the most common is embryonal rhabdomyosarcoma (ERMS) or sarcoma botryoides, a rare subtype of ERMS. These occur in infants and young children, clinically appearing as soft nodular lesions.[15]
Pathophysiology
Like the premalignant cervical lesions and carcinoma of the cervix, continual HPV infection, especially the HPV 16 subtype, is associated with the long-term development of high-grade squamous intraepithelial lesions (HSIL) and carcinoma of the vagina. The squamous cells of the vaginal mucosa are similar to the cells of the ectocervix. Recently, the terminology for precancerous lesions has changed from the vaginal intraepithelial lesion (VAIN) 1 to the low-grade squamous intraepithelial lesion and VAIN 2-3 to the high-grade squamous intraepithelial lesion. Because the vaginal epithelium does not transform via squamous metaplasia, vaginal tissue less commonly undergoes malignant transformation from HPV infection. Primary melanomas arising from the female reproductive system are uncommon and aggressive cancers. The vulva is the most frequent site (70%), followed by the vagina and, more rarely, the cervix.[16] Tumors that involve the vagina or cervix are strongly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive surgical margins, lymph node metastasis, and poor long-term clinical outcomes, including death.[17]
Histopathology
Approximately 90% of all primary vaginal cancers are SCC. Primary adenocarcinoma of the vagina is quite rare. DES-related clear cell carcinoma of the vagina occurred mainly in young women, but DES-related tumors are becoming rare as the DES-exposed cohort ages.[18] Histopathologic grades (G) are given to cancers to provide prognostic information about the tumor.
- GX: Grade cannot be assessed
- G1: Well differentiated
- G2: Moderately differentiated
- G3: Poorly or undifferentiated
Verrucous carcinoma histologically is composed of large papillary fronds covered by dense keratin. It has relatively indistinct borders in the deep margins as opposed to the well-demarcated borders of benign condyloma acuminate.[14] A small percentage of patients with vaginal cancer are diagnosed with sarcoma and melanoma. Primary vaginal melanoma is a rare mucosal neoplasm and is more aggressive than cutaneous melanoma.[19]
History and Physical
In addition to a complete medical and surgical history, attention should be given to any history of pelvic neoplasia or other malignancy. The most common presenting symptom of vaginal cancer is abnormal vaginal bleeding.[20] However, up to 20% of women may be asymptomatic and discovered on pelvic examination or with cytology for cervical cancer screening. Other nondescript symptoms may be present, such as watery, malodorous, or blood-tinged vaginal discharge.[21] Patients may report a vaginal mass, and local extension of vaginal cancer can present as urinary or gastrointestinal symptoms. Pelvic pain is often indicative of advanced disease. One of the most important aspects of the patient's history is the preexistence of cervical cancer. In a retrospective study, vaginal cancer was the most common metachronous malignancy after a cervical cancer diagnosis.[22] Evaluation for suspected vaginal cancer requires a thorough physical exam, including a digital exam, a rectovaginal exam, a speculum exam, palpation of inguinal nodes, and colposcopy with biopsies. Visualizing the entire vagina by rotating the speculum to expose anterior and posterior surfaces is important. Applying Lugol solution (iodine) during colposcopy can help visualize vaginal neoplasia.[23] It is also important to determine whether or not the patient has been appropriately vaccinated, as a reduction of vaginal neoplasia after HPV DNA vaccination has been described.[24]
Evaluation
There are no routine screening indications for vaginal cancer. If cervical cytology is abnormal and no cervical lesions are seen, evaluation for vaginal lesions should be undertaken. Vaginal cytology after hysterectomy for benign disease is not indicated due to low yield and high false positive rates. However, long-term surveillance is suggested after a hysterectomy for high-grade cervical intraepithelial neoplasia. This is especially true for immunologically compromised individuals.[25][26] Low-grade VAIN does not require treatment and can be followed with cytology and colposcopy.[27]
Biopsy remains the gold standard for diagnosing vaginal cancer. An examination under anesthesia can best accomplish this and should include inspection of the vaginal fornices and biopsies of the cervix. Clinical evaluation without anesthesia can also be performed if the patient is comfortable. Staging is essential to developing a treatment plan if a primary invasive lesion is discovered. The current staging systems include the International Federation of Gynecology and Obstetrics (FIGO) staging, Tumor, Node, Metastasis (TNM) staging, and the American Joint Commission on Cancer (AJCC) staging.[28] Treatment planning may be modified based on imaging studies. Staging includes data from the physical examination, cystoscopy, proctoscopy, and chest and skeletal radiography. A biopsy of lymph nodes may be included in the TNM staging, as well as data from a final resected specimen. No specific lab abnormalities exist for diagnosing vaginal cancer; elevated liver function tests can suggest metastatic disease but are nonspecific.
Magnetic resonance imaging (MRI) of the pelvis is useful in staging vulval and vaginal neoplasms to assess tumor size, local tumor extent, and the presence of lymph node metastases. Further indications for MRI are the diagnosis of post-therapeutic changes and tumor recurrence.[29] Although imaging studies have limited utility in diagnosing vaginal cancer, FIGO encourages using computed tomography, MRI, and positron emission tomography (PET), to guide therapy. However, the imaging findings may not be used to change or reassign the stage.[30] In 1 study, FIGO evaluated the use of PET/CT to assess suspected or known disease (primary or recurrent). They reported a change in prognostic impression and intended patient management in 51% and 36% of studies performed, respectively.[31] It is essential to understand that the vaginal lymphatic system is extensive. The middle to upper vagina drains with the cervical lymphatics into the pelvic obturator node, the internal and external iliac chains, and the para-aortic nodes. Of note, the inguinal nodes are the first drainage from the distal third of the vagina, then to the pelvic nodes. The posterior wall lymphatics drain with the rectal lymphatics.[32]
Treatment / Management
Early vaginal cancers are generally treated with surgery or radiation therapy. Advanced cancers are treated with radiation therapy and the simultaneous administration of combined chemotherapy; surgery has a limited role due to the proximity of the bladder, urethra, and rectum.[20] It may be helpful in small stage I and II tumors or more extensive surgery in patients with a fistula from late-stage disease or recurrence after radiation.[33] Local excision may be possible for small (<2 cm) lesions confined to the mucosa. For upper vaginal disease, radical hysterectomy (if the uterus is present) plus radical vaginectomy and pelvic lymphadenectomy is an option. For lower vaginal disease, radical excision with groin node dissection is a treatment option. The goal for lower and upper disease is 1 cm disease-free margins.[34] Radical surgery for stage I and II cancers has reported good outcomes; however, the series is small and retrospective.[35] A literature review reported that early-stage disease had a mean 5-year survival rate of 77%.[12] Pelvic exenteration may be offered in central recurrences after radiation, but the significant risks and morbidity need to be addressed with the patient before taking this approach. Palliative surgery for fistulas may be necessary.[34][36](B2)
A study from the National Cancer Database showed the use of combined chemoradiation therapy (CCRT) for patients with vaginal cancer has increased and is associated with a significant improvement. CCRT should be incorporated into treatment guidelines for vaginal cancer.[37] Enough success in treating cervical cancer with CCRT has moved the modality to vaginal cancer. Due to the rarity of vaginal cancer, data is limited for CCRT compared to radiation therapy alone. However, a 2013 retrospective review of 71 patients demonstrated a disease-free and overall survival benefit from combined therapy.[38] Standard therapy for locally advanced vaginal cancer generally consists of combined external beam radiation therapy (EBRT) and brachytherapy, plus weekly cisplatin-based therapy.[39][40](B2)
Vaginal melanoma is rare, and there is no standard treatment. Surgery for excision, including exenterative surgery, has been reported, and there is limited evidence to support adjuvant therapy. The use of targeted therapy such as PD-L1 blockade has increased and improved prognosis in cutaneous melanoma; however, vaginal melanoma has a different genetic profile with fewer BRAF mutations and more c-KIT mutations.[41] Individualized treatment of high-grade VAIN can prevent malignant conversion. Reported treatment modalities include laser ablation, surgical excision, and topical treatments such as imiquimod and topical chemotherapy with 5-fluorouracil.[27](B2)
Differential Diagnosis
The differential diagnosis for vaginal cancer is diverse and can include lesions not typical of the reproductive system. Sexually transmitted infections, such as herpes simplex and syphilis, can cause lesions that can mimic cancer. Vaginal trauma and atrophy can also present with bleeding similar to vaginal cancer. Benign vaginal masses include but are not limited to polyps, Gartner duct cysts, Bartholin gland cysts, and vaginal adenosis. From an oncologic perspective, cervical and vulvar cancer must be ruled out when determining if a lesion is a primary vaginal carcinoma. Metastatic lesions from the bladder and colorectal cancer have been reported.[42]
Surgical Oncology
Surgical management can be considered in stage I lesions that are amenable to hysterectomy with upper vaginectomy and lymph node dissection. Ideally, the lesions be present in the apex of the posterior fornix of the vagina. Lower lesions can be approached with vulva-vaginectomy, but this procedure is uncommon due to its complex nature and associated complications. For young women with vaginal cancer requiring radiation as primary treatment, ovarian transposition can be offered before definitive radiation treatment to prevent the adverse effects of radiation-induced menopause. In selected patients, laparoscopic or extraperitoneal removal of bulky lymph nodes can be done as part of staging and treatment planning.[1]
Radiation Oncology
Radiation is the cornerstone of treatment for vaginal cancer, particularly in advanced stages. It combines EBRT and intracavitary radiotherapy or brachytherapy. The principal advantage of radiation is organ preservation. The standard of care EBRT to the pelvis includes the external iliac and obturator nodes. Additionally, the inguinal nodes may be included if the tumor is in the distal vagina.[1] Careful treatment planning to cover the tumor area, the involved region(s), and the lymph nodes is essential for the best outcomes. The integration of computed tomography and MRI has been shown to aid in proper radiation treatment.[38] A dose of at least 70 Gy improves outcomes.[43] CCRT for patients with vaginal cancer has increased and has demonstrated significant improvement in survival in several studies. In a National Cancer Database study of 13,689 patients, the median overall survival was 56.2 months with CCRT and 41.2 months with radiation alone (p<0.0005).[37] Radiation treatment is contraindicated in patients with verrucous carcinoma because it can provoke anaplastic transformation and worsen the prognosis.[14]
Pertinent Studies and Ongoing Trials
Due to its rarity, there are currently no randomized trials regarding vaginal cancer treatment.
Toxicity and Adverse Effect Management
In a review of 138 patients treated for vaginal cancer from the Korean Radiation Oncology Group, 12% had grade 3 or 4 acute toxicity, including skin, gastrointestinal, and genitourinary. Twelve patients (8%) showed late toxicity. The volume of the tumor and FIGO stage were foreboders of severe late toxicity. Ultimately, the data showed that a later stage of disease was associated with a worse survival outcome and more toxicity from treatment.[44] In extrapolation from radiotherapy for cervical cancer, vaginal toxicity from radiation for vaginal cancer includes the following: dryness (18-21%), shortening (15-22%), tightening (16-22%), dyspareunia (9-21%), and compromised enjoyment (37-47%). Hormone replacement therapy in this study showed significant improvement in alleviating symptoms.[45] Vaginal dilator therapy is recommended for women undergoing pelvic radiation to prevent vaginal stenosis; however, no standard protocols exist. A recent expert opinion suggests starting dilation around 4 weeks after treatment, using it 2 or 3 times per week for 1 to 3 minutes, and continuing it for up to a year. Using plastic dilators of varying sizes had the best outcomes.[46] Literature suggests that a multidisciplinary clinic for sexual health may be beneficial after pelvic radiotherapy.[47]
Medical Oncology
The use of chemotherapy in vaginal cancer is relatively new, and most research has been extrapolated from data on cervical cancer treatment. Treatment with cisplatin or 5-fluorouracil has demonstrated some efficacy.[48] Chemoradiation can be considered in the management plan of vaginal cancer following a recent retrospective review suggesting an encouraging improvement in overall and disease-free survival rates.[38] Although it was a small review of 71 patients, a significant difference was shown in overall survival and disease-free survival rates between women who received radiation alone versus those who received chemoradiation as initial treatment (3-year overall survival of 56% versus 79% and 3-year disease-free survival of 43% versus 73%).[38] Limited studies on chemotherapy for recurrent vaginal cancer are available. Benefits and toxicity should be carefully considered when using systemic chemotherapy for these patients. Data on the use of chemotherapy is mainly from case reports. Cisplatin is the most common agent reported, and immunotherapy with pembrolizumab and nivolumab has been reported in a small number of patients. The poor prognosis for recurrent or stage IV disease may encourage further investigation of these agents.[5]
Staging
Staging (modified from American Cancer Society)
- Stage I- limited to the vaginal mucosa
- Stage II- involvement of the subvaginal tissue without extension to the pelvic sidewall
- Stage III- extension to the pelvic sidewall
- Stage IVA- spread to adjacent organs
- Stage IVB- spread to distant organs
| AJCC | TNM | FIGO | Description |
| IA |
T1a N0 M0 |
I |
The cancer is limited to the vagina and is no larger than 2.0 cm (T1a). It does not involve lymph nodes (N0) or distant sites (M0). |
| IB |
T1b N0 MO |
I |
The cancer is limited to the vagina but is larger than 2.0 cm (T1b). It does not involve lymph nodes (N0) or distant sites (M0). |
| IIA |
T2a N0 M0 |
II |
Cancer has spread to the connective tissues next to the vagina, but not as far as the pelvic wall, and is no larger than 2.0 cm (T2a). It has not spread to nearby lymph nodes (N0) or distant sites (M0). |
| IIB |
T2b N0 M0 |
II |
Cancer has spread to the connective tissues next to the vagina, but not as far as the pelvic wall, but is larger than 2.0 cm (T2b). It has not spread to nearby lymph nodes (N0) or distant sites (M0). |
| III |
T1 to T3 N0/N1 M0 |
III |
Cancer can be any size and has spread to the pelvic side wall and/or has caused hydronephrosis (T1 to T3). It has also spread to nearby lymph nodes in the pelvis or groin (inguinal) area (N1) but not distant sites (M0). It may also be N0. |
| IVA |
T4 Any N M0 |
IVA |
Cancer involves the bladder or rectum or is present out of the pelvis (T4). It might or might not have spread to pelvic or inguinal lymph nodes (any N). It has not spread to distant sites (M0). |
| IVB |
Any T Any N M1 |
IVB |
Cancer can be any size and has spread to distant organs (lung, liver, bone) M1. It may invade adjacent organs. It might or might not have spread to pelvic or inguinal lymph nodes (any N). |
In a recent study of 124 patients, data revealed the following distribution: Stage I - 31%, Stage II - 36%, Stage III - 16%, and Stage IV - 17%.[49]
Prognosis
Many prognostic factors can influence the management plan. Lymph node metastasis is an important prognostic factor. Other factors include histology, size, and the patient's age. In a Surveillance, Epidemiology, and End Results analysis of more than 2000 patients, the 5-year disease-specific survival was 84% for stage I, 75% for stage II, and 57% for advanced tumors.[20]
Complications
Complications from the treatment of vaginal cancer depend on many factors and can be divided into treatment-based and patient-based. Treatment-based factors include radiation intensity, type of surgery, and type of chemotherapy. Patient-based factors include age, hormonal status, and personal hygiene. The complications from radiation include edema, erythema, and mucositis with or without ulceration. Usually, these effects resolve within a few months after treatment. See the Toxicity and Side Effect Management section.
Deterrence and Patient Education
A cross-sectional survey of outpatient visits showed female patients with cancer have unmet sexual and vaginal health needs. Preferences for receiving sexual health information vary by age. Improved physician-patient communication, awareness, and educational resources using proven sexual health promotion strategies can help women cope with treatment side effects.[50]
Enhancing Healthcare Team Outcomes
Gynecologic cancers require an interprofessional team-based approach, especially in patients with a rare disease such as vaginal cancer. Once the diagnosis is made, coordinated care should involve social workers, nurse navigators, radiation oncologists, and gynecologic oncologists.[20] Ideally, vaginal cancer should be reviewed at case-based conferences. Interprofessional team members can include gynecologic oncology, plastic surgery, urology, radiation oncology, and operations staff. It is essential to coordinate with outpatient nurses, clinical nurse specialists, physician assistants, administrative assistants, physical medicine and rehabilitation specialists, social workers, sexual counselors, and the cancer survivorship practice.[51]
Clinical nurse specialists assist the team by providing psychological support to the patients living with cancer and their caregivers.[52] Their role in interprofessional care has contributed successfully where medical factors (complex comorbidities) or non-medical factors (patient preference) impact treatment.[53] Nurses assist in the evaluation and can assist during surgical procedures. They can also coordinate activities between different specialists and counsel patients. When chemotherapy is part of the treatment regimen, specialized oncology pharmacists are a valuable asset to the team, helping to direct agent selection and dosing, performing medication reconciliation, and counseling patients on what to expect from their medication regimen.
The issue of sexuality and sexual dysfunction is important, especially with treatment for vaginal cancer. Both physical and psychological issues need to be addressed; common patient complaints include lack of sexual desire, dyspareunia, decreased sensation in the genital area, and the inability to achieve orgasm.[54] An interprofessional approach focusing on the physical and psychosexual aspects of sexuality is needed to treat sexual difficulties effectively.[55] Pain management during and after therapy is essential, especially in light of the current opioid crisis. Communication about pain in patients with vaginal cancer should be tailored to the individual patient experience.[56] Here again, pharmacists and nurses can make significant contributions to patient care. All care team members must maintain meticulous records so that everyone on the interprofessional team has the latest and most accurate information for patient decisions as a part of team communication. The interprofessional approach to care yields optimal patient outcomes.
References
Adams TS, Cuello MA. Cancer of the vagina. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2018 Oct:143 Suppl 2():14-21. doi: 10.1002/ijgo.12610. Epub [PubMed PMID: 30306589]
Gardner CS, Sunil J, Klopp AH, Devine CE, Sagebiel T, Viswanathan C, Bhosale PR. Primary vaginal cancer: role of MRI in diagnosis, staging and treatment. The British journal of radiology. 2015 Aug:88(1052):20150033. doi: 10.1259/bjr.20150033. Epub 2015 May 12 [PubMed PMID: 25966291]
Ng QJ, Namuduri RP, Yam KL, Lim-Tan SK. Vaginal metastasis presenting as postmenopausal bleeding. Singapore medical journal. 2015 Aug:56(8):e134-6. doi: 10.11622/smedj.2015127. Epub [PubMed PMID: 26311914]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022 Jan:72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12 [PubMed PMID: 35020204]
Kulkarni A, Dogra N, Zigras T. Innovations in the Management of Vaginal Cancer. Current oncology (Toronto, Ont.). 2022 Apr 27:29(5):3082-3092. doi: 10.3390/curroncol29050250. Epub 2022 Apr 27 [PubMed PMID: 35621640]
Siegler E, Segev Y, Mackuli L, Auslender R, Shiner M, Lavie O. Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute. The Israel Medical Association journal : IMAJ. 2016 May:18(5):286-9 [PubMed PMID: 27430086]
Smith JS, Backes DM, Hoots BE, Kurman RJ, Pimenta JM. Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstetrics and gynecology. 2009 Apr:113(4):917-924. doi: 10.1097/AOG.0b013e31819bd6e0. Epub [PubMed PMID: 19305339]
Level 1 (high-level) evidenceHaręża DA, Wilczyński JR, Paradowska E. Human Papillomaviruses as Infectious Agents in Gynecological Cancers. Oncogenic Properties of Viral Proteins. International journal of molecular sciences. 2022 Feb 5:23(3):. doi: 10.3390/ijms23031818. Epub 2022 Feb 5 [PubMed PMID: 35163748]
Level 2 (mid-level) evidenceConlon JL. Diethylstilbestrol: Potential health risks for women exposed in utero and their offspring. JAAPA : official journal of the American Academy of Physician Assistants. 2017 Feb:30(2):49-52. doi: 10.1097/01.JAA.0000511800.91372.34. Epub [PubMed PMID: 28098674]
Daling JR, Madeleine MM, Schwartz SM, Shera KA, Carter JJ, McKnight B, Porter PL, Galloway DA, McDougall JK, Tamimi H. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecologic oncology. 2002 Feb:84(2):263-70 [PubMed PMID: 11812085]
Level 2 (mid-level) evidenceCreasman WT, Phillips JL, Menck HR. The National Cancer Data Base report on cancer of the vagina. Cancer. 1998 Sep 1:83(5):1033-40 [PubMed PMID: 9731908]
Shah CA, Goff BA, Lowe K, Peters WA 3rd, Li CI. Factors affecting risk of mortality in women with vaginal cancer. Obstetrics and gynecology. 2009 May:113(5):1038-1045. doi: 10.1097/AOG.0b013e31819fe844. Epub [PubMed PMID: 19384118]
Level 2 (mid-level) evidenceFrumovitz M, Etchepareborda M, Sun CC, Soliman PT, Eifel PJ, Levenback CF, Ramirez PT. Primary malignant melanoma of the vagina. Obstetrics and gynecology. 2010 Dec:116(6):1358-1365. doi: 10.1097/AOG.0b013e3181fb8045. Epub [PubMed PMID: 21099603]
Ramzy I, Smout MS, Collins JA. Verrucous carcinoma of the vagina. American journal of clinical pathology. 1976 May:65(5):644-53 [PubMed PMID: 16535806]
Level 3 (low-level) evidenceGhaemmaghami F, Karimi Zarchi M, Ghasemi M. Lower genital tract rhabdomyosarcoma: case series and literature review. Archives of gynecology and obstetrics. 2008 Jul:278(1):65-9. doi: 10.1007/s00404-007-0503-5. Epub 2008 Apr 22 [PubMed PMID: 18427824]
Level 3 (low-level) evidenceGadducci A, Carinelli S, Guerrieri ME, Aletti GD. Melanoma of the lower genital tract: Prognostic factors and treatment modalities. Gynecologic oncology. 2018 Jul:150(1):180-189. doi: 10.1016/j.ygyno.2018.04.562. Epub 2018 May 1 [PubMed PMID: 29728261]
Udager AM, Frisch NK, Hong LJ, Stasenko M, Johnston CM, Liu JR, Chan MP, Harms PW, Fullen DR, Orsini A, Thomas DG, Lowe L, Patel RM. Gynecologic melanomas: A clinicopathologic and molecular analysis. Gynecologic oncology. 2017 Nov:147(2):351-357. doi: 10.1016/j.ygyno.2017.08.023. Epub 2017 Aug 24 [PubMed PMID: 28844540]
Hacker NF, Eifel PJ, van der Velden J. Cancer of the vagina. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2015 Oct:131 Suppl 2():S84-7. doi: 10.1016/j.ijgo.2015.06.003. Epub [PubMed PMID: 26433679]
Lee CK, Lin H, Su CF, Kok VC. Primary Vaginal Melanoma With Rhabdoid Features: A Case Report and Literature Review. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists. 2017 Sep:36(5):499-504. doi: 10.1097/PGP.0000000000000354. Epub [PubMed PMID: 28800579]
Level 2 (mid-level) evidenceShrivastava SB, Agrawal G, Mittal M, Mishra P. Management of Vaginal Cancer. Reviews on recent clinical trials. 2015:10(4):289-97 [PubMed PMID: 26411952]
Hiniker SM, Roux A, Murphy JD, Harris JP, Tran PT, Kapp DS, Kidd EA. Primary squamous cell carcinoma of the vagina: prognostic factors, treatment patterns, and outcomes. Gynecologic oncology. 2013 Nov:131(2):380-5. doi: 10.1016/j.ygyno.2013.08.012. Epub 2013 Aug 15 [PubMed PMID: 23954572]
Level 2 (mid-level) evidenceMatsuo K, Blake EA, Machida H, Mandelbaum RS, Roman LD, Wright JD. Incidences and risk factors of metachronous vulvar, vaginal, and anal cancers after cervical cancer diagnosis. Gynecologic oncology. 2018 Sep:150(3):501-508. doi: 10.1016/j.ygyno.2018.07.016. Epub 2018 Jul 24 [PubMed PMID: 30054103]
Indraccolo U, Baldoni A. A simplified classification for describing colposcopic vaginal patterns. Journal of lower genital tract disease. 2012 Apr:16(2):75-9. doi: 10.1097/LGT.0b013e318237ec82. Epub [PubMed PMID: 22227840]
Hansen BT, Campbell S, Nygård M. Long-term incidence trends of HPV-related cancers, and cases preventable by HPV vaccination: a registry-based study in Norway. BMJ open. 2018 Feb 23:8(2):e019005. doi: 10.1136/bmjopen-2017-019005. Epub 2018 Feb 23 [PubMed PMID: 29476028]
Level 3 (low-level) evidenceMbuyisa SS, Khumalo TL, Makhathini BS, Moodley J. Prevalance of abnormal vault cytology after hysterectomy for cervical intraepithelial neoplasia, Pietermaritzburg. South African family practice : official journal of the South African Academy of Family Practice/Primary Care. 2022 Mar 31:64(1):e1-e5. doi: 10.4102/safp.v64i1.5457. Epub 2022 Mar 31 [PubMed PMID: 35384680]
Egemen D, Perkins RB, Clarke MA, Guido R, Huh W, Saraiya M, Saslow D, Smith R, Unger ER, Garcia F, Wentzensen N, Cheung LC, Enduring Consensus Cervical Cancer Screening and Management Committee. Risk-Based Cervical Consensus Guidelines: Methods to Determine Management if Less Than 5 Years of Data Are Available. Journal of lower genital tract disease. 2022 Jul 1:26(3):195-201. doi: 10.1097/LGT.0000000000000685. Epub [PubMed PMID: 35763610]
Level 3 (low-level) evidenceKim MK, Lee IH, Lee KH. Clinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases. Journal of gynecologic oncology. 2018 Jan:29(1):e6. doi: 10.3802/jgo.2018.29.e6. Epub [PubMed PMID: 29185264]
Level 2 (mid-level) evidenceFIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2009 Apr:105(1):3-4 [PubMed PMID: 19322933]
Hauth EA, Kimmig R, Forsting M. [Diagnosis of vulval and vaginal neoplasms with magnetic resonance imaging]. Gynakologisch-geburtshilfliche Rundschau. 2007:47(4):226-35 [PubMed PMID: 17914269]
Rajaram S, Maheshwari A, Srivastava A. Staging for vaginal cancer. Best practice & research. Clinical obstetrics & gynaecology. 2015 Aug:29(6):822-32. doi: 10.1016/j.bpobgyn.2015.01.006. Epub 2015 Mar 4 [PubMed PMID: 25847318]
Robertson NL, Hricak H, Sonoda Y, Sosa RE, Benz M, Lyons G, Abu-Rustum NR, Sala E, Vargas HA. The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer. Gynecologic oncology. 2016 Mar:140(3):420-4. doi: 10.1016/j.ygyno.2016.01.011. Epub 2016 Jan 11 [PubMed PMID: 26790773]
Jhingran A. Updates in the treatment of vaginal cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2022 Mar:32(3):344-351. doi: 10.1136/ijgc-2021-002517. Epub [PubMed PMID: 35256422]
Level 2 (mid-level) evidenceGadducci A, Fabrini MG, Lanfredini N, Sergiampietri C. Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors. Critical reviews in oncology/hematology. 2015 Mar:93(3):211-24. doi: 10.1016/j.critrevonc.2014.09.002. Epub 2014 Oct 5 [PubMed PMID: 25476235]
Adams TS, Rogers LJ, Cuello MA. Cancer of the vagina: 2021 update. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021 Oct:155 Suppl 1(Suppl 1):19-27. doi: 10.1002/ijgo.13867. Epub [PubMed PMID: 34669198]
Jain V, Sekhon R, Giri S, Bora RR, Batra K, Bajracharya A, Rawal S. Role of Radical Surgery in Early Stages of Vaginal Cancer-Our Experience. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2016 Jul:26(6):1176-81. doi: 10.1097/IGC.0000000000000743. Epub [PubMed PMID: 27327154]
Level 2 (mid-level) evidenceStein R, Ganeshan D, Gopireddy DR, Chaudhry A, Kumar S, Bande K, Bhosale P, Lall C. Current update on vaginal malignancies. Abdominal radiology (New York). 2021 Nov:46(11):5353-5368. doi: 10.1007/s00261-021-03228-z. Epub 2021 Aug 2 [PubMed PMID: 34338815]
Rajagopalan MS, Xu KM, Lin JF, Sukumvanich P, Krivak TC, Beriwal S. Adoption and impact of concurrent chemoradiation therapy for vaginal cancer: a National Cancer Data Base (NCDB) study. Gynecologic oncology. 2014 Dec:135(3):495-502. doi: 10.1016/j.ygyno.2014.09.018. Epub 2014 Oct 2 [PubMed PMID: 25281493]
Level 2 (mid-level) evidenceMiyamoto DT, Viswanathan AN. Concurrent chemoradiation for vaginal cancer. PloS one. 2013:8(6):e65048. doi: 10.1371/journal.pone.0065048. Epub 2013 Jun 7 [PubMed PMID: 23762284]
Zhou WL, Yue YY. Radiotherapy Plus Chemotherapy Is Associated With Improved Survival Compared to Radiotherapy Alone in Patients With Primary Vaginal Carcinoma: A Retrospective SEER Study. Frontiers in oncology. 2020:10():570933. doi: 10.3389/fonc.2020.570933. Epub 2020 Dec 18 [PubMed PMID: 33392073]
Level 2 (mid-level) evidenceDi Donato V, Bellati F, Fischetti M, Plotti F, Perniola G, Panici PB. Vaginal cancer. Critical reviews in oncology/hematology. 2012 Mar:81(3):286-95. doi: 10.1016/j.critrevonc.2011.04.004. Epub 2011 May 14 [PubMed PMID: 21571543]
Dobrică EC, Vâjâitu C, Condrat CE, Crețoiu D, Popa I, Gaspar BS, Suciu N, Crețoiu SM, Varlas VN. Vulvar and Vaginal Melanomas-The Darker Shades of Gynecological Cancers. Biomedicines. 2021 Jun 30:9(7):. doi: 10.3390/biomedicines9070758. Epub 2021 Jun 30 [PubMed PMID: 34209084]
Level 2 (mid-level) evidenceNg HJ, Aly EH. Vaginal metastases from colorectal cancer. International journal of surgery (London, England). 2013:11(10):1048-55. doi: 10.1016/j.ijsu.2013.09.004. Epub 2013 Sep 27 [PubMed PMID: 24076094]
Kirkbride P, Fyles A, Rawlings GA, Manchul L, Levin W, Murphy KJ, Simm J. Carcinoma of the vagina--experience at the Princess Margaret Hospital (1974-1989). Gynecologic oncology. 1995 Mar:56(3):435-43 [PubMed PMID: 7705681]
Chang JH, Jang WI, Kim YB, Kim JH, Kim YS, Kim YS, Park W, Kim J, Yoon WS, Kim JY, Kim HJ. Definitive treatment of primary vaginal cancer with radiotherapy: multi-institutional retrospective study of the Korean Radiation Oncology Group (KROG 12-09). Journal of gynecologic oncology. 2016 Mar:27(2):e17. doi: 10.3802/jgo.2016.27.e17. Epub [PubMed PMID: 26768782]
Level 2 (mid-level) evidenceKirchheiner K, Smet S, Jürgenliemk-Schulz IM, Haie-Meder C, Chargari C, Lindegaard JC, Fokdal LU, Spampinato S, Schmid MP, Sturdza A, Mahantshetty U, Segedin B, Bruheim K, Rai B, Cooper R, Van der Steen-Banasik E, Wiebe E, Sundset M, van Limbergen E, Villafranca E, Westerveld H, Tan LT, Pötter R, Tanderup K, Nout RA, EMBRACE Collaborative Group. Impact of Vaginal Symptoms and Hormonal Replacement Therapy on Sexual Outcomes After Definitive Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: Results from the EMBRACE-I Study. International journal of radiation oncology, biology, physics. 2022 Feb 1:112(2):400-413. doi: 10.1016/j.ijrobp.2021.08.036. Epub 2021 Sep 1 [PubMed PMID: 34478833]
Bakker RM, ter Kuile MM, Vermeer WM, Nout RA, Mens JW, van Doorn LC, de Kroon CD, Hompus WC, Braat C, Creutzberg CL. Sexual rehabilitation after pelvic radiotherapy and vaginal dilator use: consensus using the Delphi method. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2014 Oct:24(8):1499-506. doi: 10.1097/IGC.0000000000000253. Epub [PubMed PMID: 25248115]
Level 2 (mid-level) evidenceLi JY, D'Addario J, Tymon-Rosario J, Menderes G, Young MR, Johung K, Ratner E, Minkin MJ, Damast S. Benefits of a Multidisciplinary Women's Sexual Health Clinic in the Management of Sexual and Menopausal Symptoms After Pelvic Radiotherapy. American journal of clinical oncology. 2021 Apr 1:44(4):143-149. doi: 10.1097/COC.0000000000000800. Epub [PubMed PMID: 33755031]
Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet (London, England). 2001 Sep 8:358(9284):781-6 [PubMed PMID: 11564482]
Level 1 (high-level) evidenceYang J, Delara R, Magrina J, Magtibay P, Langstraat C, Dinh T, Karlin N, Vora SA, Butler K. Management and outcomes of primary vaginal Cancer. Gynecologic oncology. 2020 Nov:159(2):456-463. doi: 10.1016/j.ygyno.2020.08.036. Epub 2020 Sep 22 [PubMed PMID: 32972784]
Stabile C, Goldfarb S, Baser RE, Goldfrank DJ, Abu-Rustum NR, Barakat RR, Dickler MN, Carter J. Sexual health needs and educational intervention preferences for women with cancer. Breast cancer research and treatment. 2017 Aug:165(1):77-84. doi: 10.1007/s10549-017-4305-6. Epub 2017 May 25 [PubMed PMID: 28547655]
Cook O, McIntyre M, Recoche K, Lee S. "Our nurse is the glue for our team" - Multidisciplinary team members' experiences and perceptions of the gynaecological oncology specialist nurse role. European journal of oncology nursing : the official journal of European Oncology Nursing Society. 2019 Aug:41():7-15. doi: 10.1016/j.ejon.2019.05.004. Epub 2019 May 25 [PubMed PMID: 31358260]
Level 2 (mid-level) evidenceKerr H, Donovan M, McSorley O. Evaluation of the role of the clinical Nurse Specialist in cancer care: an integrative literature review. European journal of cancer care. 2021 May:30(3):e13415. doi: 10.1111/ecc.13415. Epub 2021 Jan 26 [PubMed PMID: 33501707]
Wallace I, Barratt H, Harvey S, Raine R. The impact of Clinical Nurse Specialists on the decision making process in cancer multidisciplinary team meetings: A qualitative study. European journal of oncology nursing : the official journal of European Oncology Nursing Society. 2019 Dec:43():101674. doi: 10.1016/j.ejon.2019.101674. Epub 2019 Oct 13 [PubMed PMID: 31689677]
Level 2 (mid-level) evidenceHarris MG. Sexuality and Menopause: Unique Issues in Gynecologic Cancer. Seminars in oncology nursing. 2019 Apr:35(2):211-216. doi: 10.1016/j.soncn.2019.02.008. Epub 2019 Mar 11 [PubMed PMID: 30871843]
Boa R, Grénman S. Psychosexual health in gynecologic cancer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2018 Oct:143 Suppl 2():147-152. doi: 10.1002/ijgo.12623. Epub [PubMed PMID: 30306581]
Kurtin S, Fuoto A. Pain Management in the Cancer Survivor. Seminars in oncology nursing. 2019 Jun:35(3):284-290. doi: 10.1016/j.soncn.2019.04.010. Epub 2019 Apr 30 [PubMed PMID: 31053398]