Vaginal disease

Vaginal disease refers to disorders of the vaginal mucosa, vaginal wall and vaginal microbiota, including bacterial vaginosis, vulvovaginal candidiasis and trichomoniasis, atrophic vaginitis of the genitourinary syndrome of menopause, contact and allergic dermatitis, vaginal wall cysts, endometriotic deposits, primary vaginal cancer and metastatic tumours, and vaginismus with genito-pelvic pain penetration disorder. Symptoms such as discharge, itching, odour, pain and bleeding affect sexual health, fertility and daily life, and shame and self-treatment often produce recurrence. About 75% of women experience vulvovaginal candidiasis at least once, bacterial vaginosis affects about 20% to 30% of reproductive-aged women, trichomoniasis causes about 156 million new cases each year, and vaginal cancer, although only 1% to 2% of gynaecological malignancies, has a poor prognosis when diagnosis is delayed.

Terminology and classification

• Vaginal disease is classified by cause into infectious, inflammatory, atrophic, neoplastic, traumatic and functional groups, and several categories often coexist, such as postmenopausal atrophy with recurrent candidiasis.
• Bacterial vaginosis is named a vaginosis rather than a vaginitis because the pathology is replacement of lactobacilli by anaerobes without marked mucosal inflammation, and this distinction affects treatment and follow-up endpoints.
• Vulvovaginal candidiasis is a fungal infection, and four or more episodes per year define recurrent disease with management different from a single acute episode.
• Trichomoniasis is caused by Trichomonas vaginalis and is a sexually transmitted infection, and partners must be treated to prevent reinfection.
• Genitourinary syndrome of menopause covers vaginal atrophy, dryness, dyspareunia and urinary symptoms, and its core mechanism is oestrogen loss rather than infection, so local oestrogen is foundational.
• Vaginal intraepithelial neoplasia uses a two-tier low-grade and high-grade classification, and high-risk human papillomavirus drives most high-grade lesions.
• Primary vaginal cancer is about 1% to 2% of female genital malignancies, mostly squamous cell carcinoma, and diagnosis requires exclusion of cervical, vulvar and endometrial primary tumours.
• ICD-10 places vaginitis at N76, prolapse at N81 and vaginal cancer at C52, while intraepithelial neoplasia needs morphological codes.
• ICD-11 groups vaginal disease within genitourinary disease and subdivides by infection, inflammation, tumour and prolapse, and cross-version conversion requires official mapping.
• MeSH uses D014623 for vaginal diseases, and retrieval must add bacterial vaginosis, candidiasis, trichomoniasis and vaginal neoplasm to avoid cervical and vulvar entries.
• Vaginismus is now termed genito-pelvic pain penetration disorder, a cross-diagnosis of pain and sexual dysfunction, and the new term emphasises multifactorial pain and fear rather than muscle spasm alone.
• Vaginal fistula is classified by anatomy into vesicovaginal, rectovaginal and urethrovaginal types, with obstetric trauma, surgery and radiotherapy as main causes.
• Vaginal foreign body and trauma in children and victims of sexual violence require forensic and psychological support, not infection management alone.
• The Chinese term vaginitis is too broad because it merges bacterial vaginosis, candidiasis and trichomoniasis, and reports should state the pathogen or syndrome.

History

• In 1892 Doderlein described vaginal lactobacilli and founded vaginal microbiota research, and for more than a century lactobacilli remained the marker of healthy vaginal flora.
• In 1928 Papanicolaou developed vaginal cytology, initially to assess hormonal status and later as a tool for cervical and vaginal cancer screening.
• From 1938 to 1971 diethylstilbestrol was widely used to prevent miscarriage, and in 1971 Herbst and colleagues linked in utero exposure to vaginal clear cell adenocarcinoma in young women, prompting drug pregnancy safety regulation and vaginal tumour registries.
• In 1955 Gardner and Dukes described Haemophilus vaginitis, later reclassified around Gardnerella, and the disease was renamed bacterial vaginosis.
• In the 1970s colposcopy extended from the cervix to the vaginal wall, enabling targeted biopsy and follow-up of vaginal intraepithelial neoplasia.
• In the 1980s the causal link between high-risk human papillomavirus and lower genital tract cancer was established, and vaginal cancer and intraepithelial neoplasia entered the viral tumour framework.
• In 1983 Amsel and colleagues proposed clinical criteria for bacterial vaginosis based on discharge, pH, amine test and clue cells, and these remain the bedside standard.
• In 1991 Nugent and colleagues established a Gram stain score from 0 to 10, standardising vaginal flora assessment for research and trials.^[1]
• In the 1990s polymerase chain reaction and nucleic acid hybridisation improved pathogen detection beyond culture and microscopy.
• In the 2000s molecular sequencing revealed lactobacillus dominance in healthy vaginas, although dominant species differ between populations.
• In the 2010s vaginal microbiota transplantation and probiotics entered early study to restore lactobacillus dominance in recurrent bacterial vaginosis.
• In 2014 the United States Centers for Disease Control and Prevention updated sexually transmitted infection guidance to include partner management and resistance in bacterial vaginosis and trichomoniasis.
• In the 2020s self-collected human papillomavirus testing spread for cervical and vaginal screening and improved access in low-resource settings.
• From cytology to molecular microbiota, the history reflects a shift from single-pathogen thinking to ecological and individualised management.

Epidemiology

• Bacterial vaginosis affects about 20% to 30% of reproductive-aged women and more than 40% in parts of sub-Saharan Africa and some minority populations, reflecting socioeconomic, behavioural and hygiene factors.
• Vulvovaginal candidiasis affects about 75% of women at least once, and 5% to 8% develop recurrent infection with four or more episodes per year.
• Trichomoniasis causes about 156 million new cases each year and is the most common non-viral sexually transmitted infection, and many infected women are asymptomatic but contagious.
• More than 50% of postmenopausal women have some genitourinary atrophy, and 20% to 30% have prominent symptoms that prompt treatment.
• Primary vaginal cancer has an age-standardised incidence of about 0.4 to 0.7 per 100000 women, mostly after 60 years, with human papillomavirus-related and immunosuppression-related disease in younger women.
• Vaginal intraepithelial neoplasia has increased with cervical screening, is mostly in the upper third, and often follows treatment of cervical lesions.
• Vaginismus and genito-pelvic pain penetration disorder affect an estimated 1% to 6% of women and a higher proportion in sexual therapy clinics.
• Risk factors include at least multiple partners, unprotected intercourse, vaginal douching, smoking, immunosuppression, diabetes, oestrogen deficiency, recent antibiotics and high-risk human papillomavirus.
• Douching is an independent risk factor because it disrupts lactobacillus dominance and promotes pathogen colonisation.
• Diabetes and immunosuppression make candidiasis more frequent and persistent, and glycaemic and immune assessment are important in recurrence.
• Human papillomavirus-related vaginal cancer is more common in immunosuppressed women, and screening intervals should be shorter in human immunodeficiency virus infection.
• Bacterial vaginosis is associated with preterm birth, low birth weight, pelvic inflammatory disease and increased human immunodeficiency virus susceptibility.
• Costs include repeated visits, drugs, tests and lost work, and recurrent infection costs far more than a single episode.
• Psychological and sexual burden is underestimated, as odour, discharge and dyspareunia cause shame, avoidance and depression, and patients often self-treat and delay care.
• Geography affects pathogen spectrum and resistance, with trichomoniasis more common in low-resource settings and azole resistance rising where use is widespread.

Pathophysiology

• Healthy vaginal microbiota is dominated by lactobacilli, which produce lactic acid, hydrogen peroxide and bacteriocins to maintain low pH and inhibit pathogens, forming the core barrier.
• Bacterial vaginosis replaces lactobacilli with Gardnerella, Prevotella, Mobiluncus and other anaerobes, raises pH above 4.5 and forms biofilms that promote recurrence.
• Bacterial vaginosis lacks marked neutrophil infiltration, so discharge increases without prominent inflammation, which explains the vaginosis rather than vaginitis label.
• Candida colonises as yeast and switches to hyphae when local immunity, pH or glycogen changes, invading epithelium and causing itching, erythema and curd-like discharge.
• Trichomonas attaches to vaginal epithelium through flagella and adhesion proteins, causing punctate haemorrhage and inflammation with yellow-green frothy discharge and raised pH.
• Postmenopausal oestrogen loss reduces epithelial glycogen and lactobacilli, raises pH and thins the mucosa, producing atrophic vaginitis and dyspareunia.
• Vaginal intraepithelial neoplasia follows the same human papillomavirus mechanism as cervical disease, with E6 and E7 interfering with p53 and retinoblastoma protein and persistent infection progressing to cancer.^[2]
• Vaginal cancer has human papillomavirus-related and p53-mutant pathways, the former in younger and immunosuppressed women and the latter in older women.
• Diethylstilbestrol exposure causes clear cell adenocarcinoma through abnormal differentiation of Müllerian epithelium, with a latency of more than a decade.
• Vaginal fistula follows tissue ischaemia, necrosis and scar traction, most often after obstructed labour, hysterectomy or pelvic radiotherapy.
• Vaginismus and penetration disorder involve pelvic floor hypertonicity, fear avoidance and pain sensitisation, and a single muscle mechanism is insufficient.
• Microbiota imbalance contributes to preterm birth through ascending infection and inflammatory cytokine release, and bacterial vaginosis roughly doubles preterm risk.
• Local immunity includes secretory immunoglobulin A, antimicrobial peptides and T cell subsets, and immunosuppression or dysbiosis weakens pathogen clearance.
• Retained foreign bodies cause chronic inflammation, ulceration and fistula, and in children sexual abuse must be excluded and safeguarding initiated.

Clinical features

• Increased discharge is the most common complaint, with thin grey malodorous discharge in bacterial vaginosis, curd-like discharge in candidiasis, yellow-green frothy discharge in trichomoniasis and scanty thin discharge in atrophy.
• Itching and burning are most prominent in candidiasis, while bacterial vaginosis causes odour more than itch and trichomoniasis causes irritation and dysuria.
• Dyspareunia and postcoital bleeding suggest atrophy, inflammation, laceration or tumour, and postmenopausal symptoms require assessment of both atrophy and malignancy.
• Vaginal bleeding may arise from inflammation, atrophy, polyps, intraepithelial neoplasia or cancer, and postmenopausal bleeding especially requires exclusion of malignancy.
• A vaginal mass or prolapse sensation may be a wall cyst, leiomyoma, prolapse or tumour, and examination with imaging localises it.
• Discharge with pelvic pain and fever suggests pelvic inflammatory disease or vault infection, and after surgery or delivery raises concern for anastomotic leak and abscess.
• Complications include at least pelvic inflammatory disease, preterm birth and low birth weight, increased human immunodeficiency virus susceptibility, vaginal fistula, sexual dysfunction and psychological disorder.
• Bacterial vaginosis and trichomoniasis increase human immunodeficiency virus transmission and acquisition through local inflammation and barrier disruption.
• Infection in pregnancy can ascend to chorioamnionitis, preterm rupture and postpartum endometritis, and screening and timing affect maternal and neonatal outcomes.
• Early vaginal cancer may be asymptomatic, while advanced disease causes contact bleeding, malodorous discharge, pelvic pain and urinary or bowel difficulty and may form fistulae.
• Recurrent candidiasis is often cyclic and linked to antibiotics, menses or glycaemic variation, and the history helps identify triggers.
• Presentations differ by group, with discharge, itch and foreign body in children, candidiasis and bacterial vaginosis in pregnancy and refractory infection or tumour in immunosuppression.
• Psychological consequences include shame, sexual avoidance, partner suspicion and depression, and stigma often drives douching and worsens disease.
• Severe disease and death result mainly from metastatic vaginal cancer, pelvic sepsis and obstetric fistula complications, and early recognition and guideline care improve outcome.

Diagnosis

• Diagnosis begins with history and speculum examination to assess discharge, mucosal inflammation, ulceration and mass, with pH and amine testing recorded.
• Bedside diagnosis of bacterial vaginosis uses the Amsel criteria, with three of four findings including thin discharge, pH above 4.5, positive amine test and clue cells.
• The Nugent Gram stain score ranges from 0 to 10, and 7 or more indicates bacterial vaginosis, serving as the reference method in epidemiology and trials.
• Candidiasis requires fungal microscopy or culture, because symptoms and signs alone are insufficient, and recurrence warrants species identification and susceptibility testing.
• Trichomoniasis is best diagnosed by nucleic acid amplification, which is more sensitive than wet mount, and partners should be tested and treated.
• Vaginal pH is fundamental to distinguishing infection types, with bacterial vaginosis and trichomoniasis usually above 4.5 and candidiasis usually normal.
• Colposcopy localises and biopsies vaginal intraepithelial neoplasia, and acetic acid and Lugol iodine reveal abnormal epithelium.
• Vaginal cancer requires biopsy and staging by the International Federation of Gynaecology and Obstetrics system using tumour size, invasion and nodal status.
• Magnetic resonance imaging evaluates local invasion and nodes, and positron emission tomography screens for distant metastasis.
• Differential diagnosis includes at least bacterial vaginosis, candidiasis, trichomoniasis, atrophic vaginitis, contact dermatitis, vaginal cancer, foreign body, fistula and sexually transmitted infection.
• Contact dermatitis often follows hygiene products, condoms, spermicides or drugs, and improvement after withdrawal is an important clue.
• Atrophic vaginitis is diagnosed from age, symptoms and mucosal signs, with raised pH and reduced lactobacilli, after infection and tumour are excluded.
• Screening for vaginal intraepithelial neoplasia relies on human papillomavirus testing and cytology, and long-term follow-up is needed because recurrence is common.
• No population screening exists for vaginal cancer, and detection depends on gynaecological examination and vaginal wall inspection during cervical screening.
• Diagnostic delay is common in vaginal cancer and recurrent infection because symptoms are non-specific and self-treatment is widespread.

Management

• Treatment aims to clear pathogens, restore lactobacillus dominance, relieve symptoms, reduce obstetric and sexually transmitted complications and exclude malignancy.
• First-line bacterial vaginosis therapy is oral or intravaginal metronidazole, with intravaginal clindamycin as an alternative, and alcohol should be avoided during treatment.^[3]
• Recurrent bacterial vaginosis may use induction followed by maintenance, but long-term antibiotics raise resistance and dysbiosis concerns, making probiotics and microbiota transfer research priorities.
• Acute candidiasis uses topical azoles or single-dose oral fluconazole, and recurrent disease needs induction, weekly maintenance for months and control of diabetes and other triggers.^[3]
• Trichomoniasis is treated with metronidazole or tinidazole, partners must be treated, and failure requires assessment for resistance and longer or alternative therapy.
• Atrophic vaginitis is treated with local oestrogen such as oestriol cream or a vaginal ring, which restores epithelium and lactobacilli, while moisturisers and lubricants are non-hormonal options.
• Vaginal intraepithelial neoplasia may be treated by local excision, laser ablation, 5-fluorouracil or imiquimod according to extent, multifocality and prior cervical disease.
• Vaginal cancer is managed by surgery and radiotherapy, with local excision or brachytherapy for early disease, concurrent chemoradiotherapy for advanced disease and immunotherapy for recurrent or metastatic disease.
• Vaginal fistula requires surgical repair after assessment of vascular supply, infection and radiotherapy history, and obstetric fistula prevention depends on labour management and timely surgery.
• Vaginismus and penetration disorder use pelvic floor physical therapy, graded dilation, sex therapy and cognitive behavioural therapy, with limited benefit from drugs alone.
• Prevention includes avoiding douching, condom use, limiting partners, glycaemic control, avoiding antibiotic misuse and human papillomavirus vaccination.
• Treating bacterial vaginosis and trichomoniasis in pregnancy reduces adverse outcomes, and drug choice must consider pregnancy safety.
• Prognosis varies, with infections usually curable but recurrent, atrophy requiring long-term care and vaginal cancer survival dependent on stage and access to treatment.
• Follow-up is disease specific, with recurrence assessment and partner care in infection, long-term surveillance in intraepithelial neoplasia and imaging plus clinical review in cancer.

Research and controversies

• The mechanism of recurrent bacterial vaginosis is contested, with biofilm, partner transmission and failed ecological restoration each supported, and antibiotics alone cannot resolve it.
• Vaginal microbiota transplantation and probiotics show inconsistent early results, and strain selection, delivery route and endpoint definitions lack standards, especially for commercial products.
• Whether asymptomatic bacterial vaginosis should be treated is disputed, with one side emphasising obstetric and sexually transmitted risk and the other warning about antibiotic overuse and dysbiosis.
• The duration and optimal regimen of maintenance therapy for recurrent candidiasis lack consensus, and azole resistance plus host immunity make individualised care a research direction.
• Vaginal cancer is too rare for large randomised trials, so recommendations rely on retrospective data and evidence for stratified care of human papillomavirus-related and p53-mutant disease is limited.
• Vaginal intraepithelial neoplasia suffers both overtreatment and underdiagnosis, and management intensity and follow-up intervals differ between guidelines.
• Self-collected human papillomavirus testing improves access, but colposcopy and follow-up completion after a positive result remain difficult in low-resource settings.
• The safety of menopausal hormone therapy and local oestrogen centres on breast cancer and thrombotic risk, and systemic absorption from low-dose local oestrogen is limited but still needs individual assessment.
• Causal links between vaginal microbiota and preterm birth or human immunodeficiency virus susceptibility are unproven, and observational confounding is hard to control.
• Cultural and commercial drivers of douching make behavioural intervention difficult, and education must target both patients and retailers.
• Artificial intelligence for colposcopy and cytology performs well in studies, but external validation, liability and privacy limit adoption.
• Unmet needs include curative therapy for recurrent infection, targeted drugs for vaginal cancer, low-cost pathogen testing and sexual health education for adolescents and older women.