Medical School · Year 3 · Obgyn · includes a quiz and discussion video

Seminar 16: Cervical and Vulvar Disease

OB/GYN Clerkship

Learning Objectives

By the end of this seminar, students will be able to:

1. Classify cervical intraepithelial neoplasia using standardized terminology and correlate cytologic findings with histopathologic grades
2. Describe the natural history of HPV-related cervical dysplasia and apply evidence-based management algorithms for CIN 1, CIN 2, and CIN 3
3. Recognize the clinical presentation and FIGO staging of invasive cervical cancer and identify appropriate treatment strategies by stage
4. Differentiate among vulvar dermatoses including lichen sclerosus, lichen simplex chronicus, and lichen planus based on clinical features and histology
5. Evaluate vulvar intraepithelial neoplasia and vulvar cancer using a systematic approach to diagnosis, staging, and surgical management
6. Counsel patients on HPV vaccination schedules, efficacy data, and the role of cervical screening in cancer prevention

Seminar Outline

Section 1: Cervical Dysplasia Classification and Pathophysiology

Cervical intraepithelial neoplasia represents a spectrum of premalignant epithelial changes driven by persistent infection with high-risk human papillomavirus. The classification system grades dysplasia from CIN 1, which corresponds to mild dysplasia and is equivalent to a low-grade squamous intraepithelial lesion on cytology, through CIN 2, representing moderate dysplasia, to CIN 3, which encompasses severe dysplasia and carcinoma in situ. In Bethesda cytologic terminology, CIN 2 and CIN 3 are both categorized under high-grade squamous intraepithelial lesion. Understanding these parallel terminology systems is essential for correlating Pap smear results with colposcopic biopsy findings and formulating appropriate management plans.

The pathophysiology of cervical dysplasia centers on infection with high-risk HPV strains, most notably types 16 and 18, which together account for approximately 70 percent of cervical cancers. HPV preferentially infects the transformation zone, the dynamic area where the columnar epithelium of the endocervix undergoes squamous metaplasia to become the squamous epithelium of the ectocervix. Viral oncoproteins E6 and E7 interfere with tumor suppressor proteins p53 and Rb, respectively, leading to uncontrolled cellular proliferation. While the majority of HPV infections are transient and cleared by the host immune system within one to two years, persistent infection with high-risk strains can lead to progressive dysplasia and, over a typical timeframe of 10 to 15 years, eventual malignant transformation.

The natural history of cervical dysplasia varies significantly by grade. CIN 1 has a high rate of spontaneous regression, with approximately 60 to 70 percent of lesions resolving without intervention within two years. CIN 2 occupies an intermediate position, with regression rates of approximately 40 percent, though outcomes differ by patient age and immune status. CIN 3 has the highest risk of progression to invasive carcinoma if left untreated, with progression rates estimated at 12 to 30 percent over many years. These natural history data inform the conservative management approach to CIN 1 and the more aggressive intervention recommended for CIN 3.

Colposcopy serves as the definitive diagnostic tool for evaluating abnormal cervical cytology. During the procedure, application of 3 to 5 percent acetic acid causes abnormal epithelium to appear white, a phenomenon known as acetowhitening, due to increased nuclear protein content in dysplastic cells. Punctation refers to a stippled appearance caused by abnormal subepithelial capillary loops viewed end-on, while mosaicism describes a tile-like pattern of vessels surrounding blocks of acetowhite epithelium. Atypical vessels, which appear as irregular, branching, or corkscrew-shaped vascular patterns, are the most concerning colposcopic finding and raise suspicion for invasive disease requiring biopsy.

<image>Panel A: Histologic comparison of normal cervical epithelium, CIN 1, CIN 2, and CIN 3 showing progressive loss of cellular maturation from basal layer to surface. Panel B: Colposcopic image demonstrating dense acetowhite epithelium with sharp borders at the transformation zone after acetic acid application. Panel C: Colposcopic view of mosaic and punctation patterns indicating high-grade dysplasia with abnormal vascular architecture. Panel D: Diagram of the cervical transformation zone illustrating the squamocolumnar junction where HPV preferentially infects metaplastic epithelium.</image>

Section 2: Management of CIN 2/3 and Excisional Procedures

The management of high-grade cervical dysplasia requires a balance between adequate treatment to prevent progression to cancer and preservation of cervical function, particularly in women who desire future fertility. The loop electrosurgical excision procedure, commonly known as LEEP, has become the most widely used excisional technique for CIN 2 and CIN 3. LEEP is performed in the outpatient setting under local anesthesia and uses a thin wire loop carrying electrical current to excise the transformation zone, providing a tissue specimen for histopathologic evaluation. Cold knife conization, which involves surgical excision of a cone-shaped cervical specimen with a scalpel, is typically reserved for cases where a larger specimen is needed, glandular lesions are suspected, or margins from LEEP are positive and require re-excision.

The LEEP procedure offers several advantages that have made it the standard of care for treating high-grade dysplasia. It can be performed in an office or clinic setting with local anesthetic injection of the cervix, minimizing patient discomfort and the need for general anesthesia. The excised specimen is oriented and sent for pathologic evaluation, which confirms the histologic grade and assesses margin status, providing both diagnostic and therapeutic benefit. Complications of LEEP are generally uncommon but include bleeding, which occurs in approximately 2 to 5 percent of cases, cervical stenosis, infection, and, importantly in women of reproductive age, an increased risk of cervical insufficiency in subsequent pregnancies, particularly when large or repeated excisions are performed.

Special populations require modified approaches to the management of cervical dysplasia. During pregnancy, invasive treatment of CIN 2 or CIN 3 is deferred because excisional procedures carry risks of hemorrhage and preterm delivery. Instead, pregnant patients undergo colposcopic surveillance, with definitive treatment planned for the postpartum period, provided that invasive cancer has been excluded. Adolescents and young women aged 21 to 24 years with CIN 2 may be managed conservatively with observation and repeat testing, as regression rates are higher in this age group. Postmenopausal women may present unique challenges because the transformation zone has receded into the endocervical canal, sometimes necessitating cold knife conization rather than LEEP to obtain an adequate specimen.

Following excisional treatment for CIN 2 or CIN 3, structured surveillance is essential to detect recurrence, which occurs in approximately 5 to 10 percent of treated patients. Current guidelines recommend co-testing with HPV and cytology at 6 months post-treatment. If both tests are negative, the patient undergoes annual co-testing for three years, followed by return to routine screening intervals if all results remain negative. Patients with positive HPV results or abnormal cytology during surveillance should be referred for repeat colposcopy. Women who have been treated for CIN 2 or CIN 3 remain at elevated risk for developing cervical cancer for at least 25 years after treatment, underscoring the importance of long-term follow-up and continued screening.

<image>Panel A: Step-by-step illustration of the LEEP procedure showing wire loop excision of the transformation zone under colposcopic guidance with local anesthesia. Panel B: Gross specimen from cold knife conization demonstrating the cone-shaped tissue with oriented margins for pathologic evaluation. Panel C: Algorithm for post-treatment surveillance of CIN 2/3 showing decision points based on HPV and cytology results at 6 months, 12 months, and annually. Panel D: Comparison table of LEEP versus cold knife conization indicating specimen size, anesthesia requirements, and clinical indications for each procedure.</image>

Section 3: Cervical Cancer Epidemiology and Presentation

Cervical cancer remains the fourth most common cancer in women worldwide, with the greatest disease burden in low- and middle-income countries where screening and vaccination programs are limited. In the developed world, the incidence has declined dramatically due to effective Pap smear screening and, more recently, HPV vaccination. The major risk factors for cervical cancer include persistent high-risk HPV infection, cigarette smoking, immunosuppression from HIV or transplant medications, and high parity. The peak incidence occurs in women aged 35 to 44 years, though the disease can present at any age, and the average age at diagnosis has been decreasing in some populations due to changes in sexual behavior and HPV exposure patterns.

The histologic classification of cervical cancer is dominated by two main types. Squamous cell carcinoma accounts for 70 to 80 percent of cases and arises from the squamous epithelium of the ectocervix at the transformation zone. Adenocarcinoma, comprising 20 to 25 percent of cervical cancers, originates from the glandular epithelium of the endocervical canal and may be more difficult to detect on routine Pap smear screening because the cells of origin are located higher in the canal. Other rare histologic subtypes include adenosquamous carcinoma, small cell neuroendocrine carcinoma, and clear cell carcinoma, the last of which was historically associated with in utero diethylstilbestrol exposure.

The clinical presentation of cervical cancer varies by stage. Early-stage disease is frequently asymptomatic and detected only through screening. When symptoms occur, the most common presentation is abnormal vaginal bleeding, particularly postcoital bleeding, intermenstrual spotting, or postmenopausal bleeding. Patients may also report a watery, blood-tinged, or foul-smelling vaginal discharge. As the disease advances, pelvic pain, leg edema from lymphatic obstruction, flank pain from ureteral obstruction causing hydronephrosis, and symptoms related to bladder or rectal invasion such as hematuria or rectal bleeding may develop.

The diagnostic workup for cervical cancer begins with tissue biopsy of any visible cervical lesion, which can be performed at colposcopy or in the clinic. When the lesion is not visible but cytology suggests malignancy, or when microinvasive disease is suspected, a conization procedure is necessary to obtain adequate tissue for histologic evaluation of depth of invasion. Staging evaluation includes physical examination under anesthesia, cross-sectional imaging with CT or MRI of the pelvis and abdomen to assess tumor size, parametrial involvement, and lymph node status, and PET-CT for advanced disease to evaluate distant metastases. The 2018 FIGO staging system now allows incorporation of imaging and pathologic findings, including lymph node status, into the staging framework.

<image>Panel A: Global incidence map of cervical cancer showing highest burden in sub-Saharan Africa, Southeast Asia, and Central America compared with low rates in screened populations. Panel B: Colposcopic photograph of an exophytic cervical mass with irregular surface, contact bleeding, and abnormal vasculature consistent with invasive squamous cell carcinoma. Panel C: MRI sagittal view of the pelvis demonstrating a cervical tumor with parametrial extension and proximal vaginal involvement. Panel D: Diagram showing the progression from HPV infection through CIN 1, CIN 2, CIN 3 to invasive cervical cancer with approximate time intervals at each stage.</image>

Section 4: Cervical Cancer Staging and Treatment

The 2018 FIGO staging system for cervical cancer provides a framework for treatment planning and prognostication. Stage I disease is confined to the cervix, with stage IA representing microinvasive carcinoma subdivided by depth of stromal invasion, and stage IB encompassing clinically visible lesions or those with greater than 5 millimeters of stromal invasion, further subdivided by tumor size. Stage II indicates extension beyond the uterus but not to the pelvic sidewall, with IIA involving the upper two-thirds of the vagina and IIB indicating parametrial involvement. Stage III disease extends to the pelvic sidewall, involves the lower third of the vagina, causes hydronephrosis, or involves pelvic or para-aortic lymph nodes. Stage IV includes invasion of the bladder or rectal mucosa or distant metastatic disease.

Treatment selection for cervical cancer is determined primarily by stage, tumor size, and the presence of lymph node involvement. Stage IA1 disease without lymphovascular space invasion can be treated conservatively with cone biopsy alone in patients desiring fertility or with simple hysterectomy. Stage IA2 through IB1 disease is typically managed with radical hysterectomy including bilateral pelvic lymphadenectomy, or alternatively with primary chemoradiation, as both approaches yield equivalent survival outcomes. For larger tumors in stages IB2 through IIA, radical hysterectomy or primary chemoradiation with cisplatin as a radiosensitizer are the treatment options, with chemoradiation increasingly preferred for bulky disease. Stages IIB through IV are treated with primary chemoradiation, combining external beam radiation, intracavitary brachytherapy, and concurrent cisplatin-based chemotherapy.

Fertility-sparing options are available for carefully selected young patients with early-stage cervical cancer who desire future childbearing. Cone biopsy alone may be sufficient for stage IA1 disease without lymphovascular space invasion. Radical trachelectomy, which involves removal of the cervix with parametrial tissue while preserving the uterine corpus, is an option for patients with stage IA2 to IB1 tumors measuring less than 2 centimeters, with negative lymph nodes. This procedure allows subsequent pregnancy, though patients require cerclage placement and carry increased risks of second-trimester loss and preterm delivery. Extensive preoperative counseling regarding oncologic safety, pregnancy outcomes, and the potential need for abandonment of fertility-sparing surgery if intraoperative findings are unfavorable is essential.

Prognosis in cervical cancer correlates strongly with stage at diagnosis. Five-year survival rates for stage I disease range from 80 to 95 percent, reflecting the excellent outcomes achievable with early detection. Stage II disease carries a 60 to 80 percent five-year survival rate, while stage III drops to 30 to 50 percent as tumor volume, lymph node involvement, and local extension increase. Stage IV disease has a five-year survival of less than 20 percent. Additional prognostic factors include tumor size, histologic type and grade, depth of stromal invasion, lymphovascular space invasion, and lymph node status. Recurrent cervical cancer has limited treatment options, though immunotherapy with pembrolizumab and combination targeted therapy have shown promise in clinical trials for PD-L1-positive and microsatellite instability-high tumors.

<image>Panel A: Diagram of FIGO cervical cancer stages I through IV showing anatomic extent of disease at each stage with labeled structures including cervix, parametrium, pelvic sidewall, bladder, and rectum. Panel B: Treatment algorithm flowchart matching stage of disease to surgical versus chemoradiation approaches with decision points for tumor size and lymph node status. Panel C: Illustration of the radical trachelectomy procedure showing resection margins, preservation of the uterine corpus, and cerclage placement for fertility preservation. Panel D: Kaplan-Meier survival curves comparing five-year overall survival by FIGO stage from I through IV with corresponding survival percentages.</image>

Section 5: Vulvar Dermatoses

Lichen sclerosus is the most clinically significant vulvar dermatosis due to its chronic, progressive nature and its association with an elevated lifetime risk of vulvar squamous cell carcinoma estimated at 4 to 6 percent. The condition has a bimodal age distribution, affecting prepubertal girls and postmenopausal women most commonly. On examination, affected skin appears white, thin, and atrophic with a characteristic "cigarette paper" wrinkling quality, often distributed in a figure-of-eight pattern encompassing the vulva and perianal region. Patients typically present with intense pruritus and dyspareunia, and the diagnosis is confirmed by punch biopsy showing epidermal atrophy, hyalinization of the upper dermis, and a band-like lymphocytic infiltrate. First-line treatment consists of potent topical corticosteroids such as clobetasol propionate 0.05 percent, applied daily for several weeks then tapered to a maintenance regimen, with long-term surveillance for malignant transformation.

Lichen simplex chronicus results from a self-perpetuating itch-scratch cycle that leads to chronic thickening and lichenification of the vulvar skin. The condition may arise as a primary process or may be superimposed on an underlying dermatosis such as lichen sclerosus or contact dermatitis. On examination, the skin appears thickened, hyperpigmented, and lichenified, with exaggerated skin markings and sometimes excoriations from scratching. Intense pruritus, often worse at night, is the hallmark symptom. Treatment focuses on breaking the itch-scratch cycle through potent topical corticosteroids, nighttime antihistamines such as hydroxyzine, and behavioral modification to reduce scratching. Identification and treatment of any underlying condition is essential for long-term resolution.

Lichen planus affecting the vulva most commonly manifests as the erosive variant, which involves both vulvar and vaginal tissues and can cause significant morbidity. The condition presents with painful erosions surrounded by a white, lacy border known as Wickham striae, and patients report burning pain, severe dyspareunia, and vaginal discharge. If untreated, erosive lichen planus can lead to progressive vaginal stenosis and obliteration of the vulvar architecture. Diagnosis is confirmed by biopsy showing a band-like lymphocytic infiltrate at the dermoepidermal junction with destruction of the basal layer. Treatment involves potent topical corticosteroids, and refractory cases may require systemic immunosuppressive agents such as calcineurin inhibitors, methotrexate, or mycophenolate.

Other vulvar dermatoses that clinicians must recognize include contact dermatitis, which may be irritant or allergic in etiology and presents with erythema, edema, and pruritus in response to soaps, detergents, topical medications, or sanitary products. Vulvar psoriasis manifests as well-demarcated, erythematous plaques that may lack the typical silvery scale seen elsewhere on the body due to the moist environment. Seborrheic dermatitis of the vulva produces greasy, yellowish scales on erythematous skin. Vulvar Paget disease is a rare but important condition that presents as a red, eczematoid lesion with well-defined borders, often mimicking dermatitis, and requires biopsy for diagnosis. Unlike mammary Paget disease, vulvar Paget disease is usually an intraepithelial process, though an underlying adenocarcinoma of the apocrine glands, Bartholin gland, or genitourinary tract must be excluded.

<image>Panel A: Clinical photograph of lichen sclerosus showing white, atrophic vulvar skin with characteristic cigarette paper wrinkling and figure-of-eight distribution around the vulva and perianal region. Panel B: Clinical image of erosive lichen planus demonstrating bright red erosions of the vulvar vestibule and inner labia with surrounding white Wickham striae. Panel C: Histologic section of lichen sclerosus showing epidermal atrophy, homogenization of the upper dermis, and a band-like lymphocytic infiltrate beneath the zone of sclerosis. Panel D: Clinical photograph of vulvar Paget disease showing a well-demarcated, erythematous, eczematoid plaque on the labia majora with irregular borders.</image>

Section 6: Vulvar Intraepithelial Neoplasia

Vulvar intraepithelial neoplasia is classified into two distinct subtypes with different etiologies, patient demographics, and malignant potential. Usual-type VIN, also designated high-grade squamous intraepithelial lesion of the vulva, is HPV-related and typically affects younger women in their 30s and 40s. Differentiated VIN is not HPV-related and instead arises in the setting of chronic vulvar dermatoses, most commonly lichen sclerosus. Differentiated VIN tends to occur in older women and carries a higher risk of rapid progression to invasive squamous cell carcinoma despite its seemingly less aggressive histologic appearance. Understanding these two pathways is critical for appropriate management and surveillance.

The risk factors for vulvar intraepithelial neoplasia mirror those for its two pathogenic subtypes. Usual-type VIN shares risk factors with cervical dysplasia, including infection with high-risk HPV, particularly type 16, cigarette smoking, and immunosuppression from HIV or transplant medications. Differentiated VIN is associated with longstanding vulvar lichen sclerosus, reinforcing the importance of surveillance in patients with this chronic dermatosis. Additional risk factors include prior history of cervical or vaginal intraepithelial neoplasia, as the lower genital tract shares common susceptibility to HPV-related neoplasia, a concept referred to as the field effect of HPV infection.

The clinical presentation of VIN is variable, and a significant proportion of patients are asymptomatic, with the diagnosis made incidentally during evaluation for other vulvar complaints. When symptoms are present, pruritus is the most common complaint. On examination, VIN lesions may appear as white, red, or pigmented patches or plaques that may be flat, raised, or papillomatous. Multifocal disease is common in usual-type VIN, while differentiated VIN is more often unifocal. Any persistent vulvar lesion that does not respond to conservative treatment should be biopsied, particularly in postmenopausal women with lichen sclerosus, to exclude VIN or invasive carcinoma.

The treatment of vulvar intraepithelial neoplasia aims to eradicate the lesion while preserving vulvar anatomy and function. Wide local excision with negative margins remains the preferred treatment, as it provides a tissue specimen for histopathologic evaluation and allows exclusion of occult invasion. Laser ablation is an alternative for multifocal disease, though it does not provide tissue for pathologic analysis and should only be used after biopsy has excluded invasion. Topical imiquimod, an immune response modifier, has shown efficacy in selected cases of usual-type VIN, with complete response rates of approximately 35 to 50 percent. If VIN is left untreated, the risk of progression to invasive vulvar carcinoma is estimated at 5 to 10 percent, and long-term surveillance at 6- to 12-month intervals is recommended regardless of the treatment modality employed.

<image>Panel A: Clinical photograph of multifocal usual-type VIN showing raised, hyperpigmented papular lesions distributed across the labia and perineum in a younger woman. Panel B: Clinical photograph of differentiated VIN arising within a background of lichen sclerosus, showing a focal raised lesion with irregular surface on the inner labia. Panel C: Histologic comparison of usual-type VIN showing full-thickness epithelial atypia with mitotic figures versus differentiated VIN showing basal atypia with overlying differentiated epithelium. Panel D: Treatment algorithm for VIN displaying decision pathways based on lesion type, extent, and patient factors including excision, laser ablation, and topical imiquimod options.</image>

Section 7: Vulvar Cancer

Vulvar cancer accounts for approximately 4 percent of all gynecologic malignancies and predominantly affects elderly women, with a peak incidence in the seventh and eighth decades of life. Squamous cell carcinoma is the dominant histologic type, comprising approximately 90 percent of cases, followed by melanoma, Bartholin gland carcinoma, basal cell carcinoma, and sarcoma. Two distinct pathogenic pathways have been identified: the HPV-related pathway, which tends to affect younger women and arises through usual-type VIN, and the lichen sclerosus-associated pathway, which occurs in older women through differentiated VIN. These pathways have different molecular profiles, with HPV-related tumors generally carrying a better prognosis.

The clinical presentation of vulvar cancer is often delayed because patients and clinicians may attribute symptoms to benign vulvar conditions. The most common presenting features include a palpable mass or visible ulcer on the vulva, longstanding pruritus that may predate the malignancy by years, vulvar bleeding, and pain of variable intensity. The labia majora is the most common site of involvement, though lesions can occur anywhere on the vulva, including the labia minora, clitoris, and perineum. On examination, the lesion may appear as a raised, exophytic mass, a flat ulcer with indurated edges, or a verrucous growth. Any vulvar lesion that does not resolve with appropriate treatment should undergo biopsy.

The FIGO staging system for vulvar cancer categorizes disease extent to guide treatment planning. Stage I disease is confined to the vulva with tumor size of 2 centimeters or less and stromal invasion of 1 millimeter or less for stage IA. Stage II encompasses larger tumors or those with extension to adjacent perineal structures including the lower urethra, lower vagina, or anus. Stage III indicates metastasis to inguinofemoral lymph nodes, with subcategories based on the number and size of involved nodes and the presence or absence of extracapsular spread. Stage IV includes invasion of the upper urethra, bladder mucosa, rectal mucosa, or pelvic bone, or distant metastatic disease.

The treatment of vulvar cancer is primarily surgical. Early-stage disease is managed with wide local excision or radical vulvectomy, with the extent of surgery tailored to achieve adequate margins of at least 1 centimeter while preserving as much normal tissue as possible. Sentinel lymph node biopsy has become the standard approach for assessing inguinofemoral lymph node status in tumors with greater than 1 millimeter of invasion, reducing the morbidity of complete inguinofemoral lymphadenectomy while maintaining oncologic safety. For patients with positive lymph nodes or advanced disease, adjuvant radiation therapy with or without concurrent chemotherapy is recommended. Primary chemoradiation with cisplatin and 5-fluorouracil is used for locally advanced tumors that would require exenterative surgery, with the goal of tumor shrinkage followed by less radical surgical excision.

<image>Panel A: Clinical photograph of a vulvar squamous cell carcinoma presenting as an ulcerated, irregular mass on the left labium majus with raised, indurated borders. Panel B: Diagram of FIGO vulvar cancer stages I through IV showing progressive involvement from vulva-confined disease through inguinofemoral nodal spread to adjacent organ invasion. Panel C: Intraoperative photograph demonstrating sentinel lymph node biopsy with blue dye mapping of the inguinofemoral lymph node basin during vulvar cancer surgery. Panel D: Axial CT image of the pelvis showing bilateral enlarged inguinal lymph nodes with central necrosis consistent with metastatic vulvar squamous cell carcinoma.</image>

Section 8: Cervicitis and Benign Cervical Lesions

Cervicitis is an inflammatory condition of the cervix most commonly caused by sexually transmitted pathogens, particularly Chlamydia trachomatis and Neisseria gonorrhoeae, though herpes simplex virus, Trichomonas vaginalis, and Mycoplasma genitalium may also be responsible. On speculum examination, cervicitis manifests as mucopurulent endocervical discharge with cervical friability, meaning the cervix bleeds easily on contact with a swab or spatula. Many patients are asymptomatic, while others report intermenstrual bleeding, postcoital bleeding, or dysuria. Diagnosis is confirmed by nucleic acid amplification testing for chlamydia and gonorrhea, and empiric antibiotic treatment is initiated based on the likely pathogen while awaiting test results. Partner notification and treatment are essential components of management.

Cervical ectropion, also known as cervical ectopy, is a normal physiologic variant in which the columnar epithelium of the endocervical canal is visible on the ectocervix. This condition is most commonly seen in adolescents, women taking combined oral contraceptive pills, and pregnant women due to the effects of estrogen on the cervical epithelium. On examination, ectropion appears as a red, velvety area surrounding the cervical os that may be mistaken for cervicitis or early malignancy. The tissue is fragile and may bleed on contact. Cervical ectropion is a benign condition that generally requires no treatment, though cauterization with silver nitrate or electrocautery may be considered in patients with persistent symptomatic bleeding or excessive mucoid discharge.

Cervical polyps are common benign growths arising from the endocervical canal that protrude through the cervical os. They are found most frequently in multiparous women in their 40s and 50s and may be detected incidentally during routine pelvic examination or present with intermenstrual spotting, postcoital bleeding, or increased mucoid discharge. Most cervical polyps are small, pedunculated, and smooth-surfaced, arising from a slender stalk of endocervical tissue. The risk of malignant transformation is very low, estimated at less than 1 percent, but all removed polyps should be sent for histopathologic examination. Polypectomy is typically performed in the office by grasping the polyp base with ring forceps and twisting to avulse the stalk, with application of silver nitrate or Monsel solution to the base for hemostasis.

Nabothian cysts are mucus-retention cysts that form when squamous epithelium grows over the openings of endocervical glands during the normal process of squamous metaplasia at the transformation zone, trapping mucus within the gland. These cysts appear as smooth, round, yellow or translucent bumps on the cervical surface and range from a few millimeters to over a centimeter in diameter. Nabothian cysts are exceedingly common, particularly in parous women, and are considered an entirely normal finding on pelvic examination. They are asymptomatic and require no treatment. Their clinical significance lies in distinguishing them from other cervical lesions; awareness that nabothian cysts are benign prevents unnecessary biopsy or patient anxiety when they are discovered during routine examination.

<image>Panel A: Speculum examination photograph showing mucopurulent endocervical discharge with cervical friability consistent with infectious cervicitis requiring NAAT testing. Panel B: Clinical photograph of cervical ectropion demonstrating the red, granular appearance of columnar epithelium visible on the ectocervix surrounding the external os. Panel C: Photograph of an endocervical polyp protruding through the cervical os, showing a smooth, glistening, pedunculated mass on a slender stalk. Panel D: Photograph of multiple nabothian cysts on the cervical surface appearing as smooth, round, yellow-white retention cysts of varying sizes.</image>

Section 9: Vaginal Disorders

Genitourinary syndrome of menopause, previously known as vulvovaginal atrophy or atrophic vaginitis, is a chronic and progressive condition resulting from estrogen deficiency that affects the vulva, vagina, urethra, and bladder. Unlike vasomotor symptoms which typically improve over time, GSM worsens without treatment and affects up to 50 percent of postmenopausal women. The most common symptoms are vaginal dryness, which is reported by the majority of affected women, followed by dyspareunia, vaginal burning or irritation, and thin watery discharge. On examination, the vaginal epithelium appears pale, thin, smooth, and lacking the normal rugal folds, with petechiae indicating tissue fragility and an elevated vaginal pH above 5. Treatment options include vaginal lubricants for use during intercourse, regular vaginal moisturizers, and most effectively, low-dose vaginal estrogen in the form of cream, tablet, or ring, which is considered safe even in many patients with relative contraindications to systemic hormone therapy.

Vaginal cancer is one of the rarest gynecologic malignancies, accounting for only 1 to 2 percent of all gynecologic cancers. Squamous cell carcinoma is the most common histologic type, followed by adenocarcinoma, melanoma, and sarcoma. Risk factors include HPV infection, prior history of cervical intraepithelial neoplasia or cervical cancer, prior pelvic radiation, immunosuppression, and historically, in utero exposure to diethylstilbestrol. Patients typically present with painless vaginal bleeding, often postmenopausal, watery or blood-tinged vaginal discharge, or a palpable vaginal mass. Treatment is primarily radiation-based, with external beam radiation and intracavitary brachytherapy for most stages, as the close proximity of the vagina to the bladder and rectum limits the role of radical surgery.

Vaginal intraepithelial neoplasia is a premalignant condition of the vaginal epithelium strongly associated with HPV infection. VAIN frequently coexists with cervical or vulvar intraepithelial neoplasia, reflecting the multicentric field effect of HPV on the lower genital tract. The condition is most commonly detected through abnormal Pap smear findings in women who have undergone hysterectomy for CIN 3 or who have a history of HPV-related neoplasia. VAIN is graded from 1 to 3, with VAIN 1 managed conservatively with observation and VAIN 2/3 treated with excision, laser ablation, or topical 5-fluorouracil. Long-term colposcopic surveillance of the vaginal cuff and vaginal walls is essential, as recurrence is common and progression to invasive vaginal carcinoma can occur.

Gartner duct cysts are benign vaginal wall cysts that arise from embryologic remnants of the Wolffian (mesonephric) duct system. They are located along the anterolateral vaginal wall, corresponding to the developmental path of the mesonephric duct, and may be found incidentally during routine pelvic examination. Most Gartner duct cysts are small, asymptomatic, and require no treatment. When they enlarge, they may cause a sense of vaginal fullness, dyspareunia, or difficulty with tampon insertion. The differential diagnosis of vaginal wall cysts includes Bartholin duct cyst, which is located at the posterolateral introitus, endometriotic cyst, and epithelial inclusion cyst, which is the most common vaginal wall cyst and typically occurs at sites of prior vaginal trauma or episiotomy. Surgical excision of a Gartner duct cyst is only indicated when the cyst is symptomatic or growing.

<image>Panel A: Clinical photograph of vaginal atrophy demonstrating pale, smooth, thin vaginal epithelium with loss of rugae, petechiae, and introital narrowing in a postmenopausal patient. Panel B: Colposcopic photograph of vaginal intraepithelial neoplasia showing acetowhite lesions on the vaginal wall after acetic acid application in a patient with prior hysterectomy for CIN 3. Panel C: Transvaginal ultrasound image of a Gartner duct cyst appearing as a well-circumscribed, anechoic cystic structure along the anterolateral vaginal wall. Panel D: MRI sagittal image demonstrating a vaginal carcinoma presenting as an enhancing mass in the posterior vaginal wall with preserved tissue planes between the tumor and the rectum.</image>

Section 10: HPV Vaccination

The nonavalent HPV vaccine, marketed as Gardasil 9, is the current standard for HPV immunization and provides protection against nine HPV types: 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are responsible for approximately 90 percent of genital warts, while types 16 and 18 together cause about 70 percent of cervical cancers, and the additional high-risk types 31, 33, 45, 52, and 58 account for another approximately 20 percent. This expanded coverage means the nonavalent vaccine has the potential to prevent up to 90 percent of cervical cancers when combined with the high-risk types covered. The vaccine consists of virus-like particles produced by recombinant technology that generate a robust immune response without any risk of infection, as they contain no viral DNA.

The Advisory Committee on Immunization Practices recommends routine HPV vaccination at age 11 to 12 years, though it may be administered as early as age 9. For individuals who initiate the vaccine series before age 15, only two doses are required, administered 6 to 12 months apart. Those who begin the series at age 15 or older, or who are immunocompromised, require three doses given at 0, 1 to 2, and 6 months. Catch-up vaccination is recommended through age 26 for all individuals who have not been adequately vaccinated. For adults aged 27 to 45 years who have not been previously vaccinated, shared clinical decision-making between the patient and provider is recommended, taking into account the individual's risk factors and the diminishing benefit of vaccination with increasing age and prior HPV exposure.

The efficacy of HPV vaccination has been demonstrated in both clinical trials and real-world population-level data. Studies have shown greater than 90 percent reduction in cervical dysplasia caused by vaccine-type HPV in vaccinated populations, and countries with high vaccination coverage have observed dramatic declines in cervical cancer incidence. Beyond cervical cancer, the vaccine provides significant protection against vulvar and vaginal intraepithelial neoplasia, anal cancer, oropharyngeal cancer, and genital warts. Real-world data from Australia, which implemented a national vaccination program in 2007, has demonstrated near-elimination of genital warts in young women and men, along with significant reductions in high-grade cervical abnormalities, providing compelling evidence for the transformative public health impact of HPV vaccination.

The safety profile of HPV vaccination is well established through extensive clinical trials and post-marketing surveillance involving hundreds of millions of administered doses worldwide. The most common adverse effects are injection site reactions including pain, redness, and swelling, which are mild and self-limited. Syncope can occur following vaccination, particularly in adolescents, and patients should be observed for 15 minutes after injection. There are no serious safety concerns associated with the vaccine, and large pharmacovigilance studies have found no association between HPV vaccination and autoimmune disease, Guillain-Barre syndrome, or other serious adverse events. The vaccine is contraindicated only in individuals with a severe allergic reaction to a prior dose or to a vaccine component, including yeast. Vaccination is not recommended during pregnancy, though inadvertent administration during pregnancy has not been associated with adverse outcomes, and the series can be completed postpartum.

<image>Panel A: Diagram of the nonavalent HPV vaccine showing the nine virus-like particles corresponding to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 with color-coded risk categorization for warts versus cancer. Panel B: Vaccination schedule chart comparing the two-dose regimen for patients under 15 years with the three-dose regimen for patients 15 years and older, showing recommended time intervals. Panel C: Bar graph displaying the percent reduction in cervical cancer, genital warts, VIN, VAIN, and anal cancer achieved with HPV vaccination based on clinical trial and population-level data. Panel D: Population-level trend graph from Australia showing declining rates of high-grade cervical abnormalities and genital warts in young women following introduction of the national HPV vaccination program.</image>

Summary

• CIN is an HPV-driven spectrum from mild dysplasia (CIN 1) through carcinoma in situ (CIN 3), with CIN 1 having high spontaneous regression rates and CIN 2/3 requiring excisional treatment such as LEEP
• Cervical cancer is the fourth most common cancer in women worldwide, with squamous cell carcinoma comprising 70 to 80 percent of cases and staging determining treatment from conization to chemoradiation
• FIGO cervical cancer staging ranges from stage I (cervix confined) through stage IV (distant metastases), with five-year survival declining from 80 to 95 percent in stage I to less than 20 percent in stage IV
• Lichen sclerosus presents as white, atrophic vulvar skin in a figure-of-eight distribution with a 4 to 6 percent lifetime malignancy risk, treated with potent topical corticosteroids and long-term surveillance
• VIN is classified as usual type (HPV-related, younger women) or differentiated type (lichen sclerosus-associated, older women), with excision as the preferred treatment and 5 to 10 percent malignancy risk if untreated
• Vulvar cancer is predominantly squamous cell carcinoma (90 percent) managed with wide local excision and sentinel lymph node assessment, with chemoradiation reserved for advanced disease
• Cervicitis is most commonly caused by Chlamydia and Neisseria gonorrhoeae, presenting with mucopurulent discharge and cervical friability, diagnosed by NAAT
• GSM is a progressive estrogen-deficiency condition causing vaginal dryness and dyspareunia, most effectively treated with low-dose vaginal estrogen
• The nonavalent HPV vaccine covers nine HPV types and provides greater than 90 percent reduction in cervical cancer when administered at age 11 to 12 years
• HPV catch-up vaccination is recommended through age 26, with shared clinical decision-making for ages 27 to 45

Key Terms

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