Vulvar invasive squamous cell carcinoma in a young patient with Human Immunodeficiency Virus-seropositivity.

Vulvar squamous cell carcinomas (SCC) are rare malignancy of unknown etiology. Only 10% of these tumors occur under the age of 40 years. We are describing one such rare case where a 29-year-old female patient had presented with nonhealing ulcer over vulva since 4 months. Histopathology revealed invasive SCC of the vulva. The occurrence of invasive vulvar SCC in a younger patient is rare. In this patient, it is most likely precipitated by immunodeficiency caused by Human Immunodeficiency Virus.

INTRODUCTION

Vulvar and vaginal squamous cell carcinomas (VV-SCC) are rare malignancies with a world-standardized annual incidence of around 1-3 per 100,000 women.[1] The disease occurs mainly among women in their 60s or 70s. The etiology of VV-SCC remains incompletely understood. Although many hypotheses have been proposed in the etiology of vulvar cancer, it has no specific factor. Historically the only common variable is a chronic itch-scratch cycle. Prior studies have reported infection with human papillomavirus (HPV) types are associated with high-risk HPVs (hrHPVs) of cervical cancer to be etiologically involved in VV-SCC.[2] Other risk factors, including lifetime number of male sexual partners, genital warts, tobacco smoking, and low socioeconomic status are involved. However, other, yet poorly defined etiologic factors that influence the risk of VV-SCC either without or in conjunction with hrHPV infection must exist.

The relationship between HPV infection and female lower genital tract neoplasia has been established in the past 20 years. During the same period of time, studies have also shown that patients infected with Human Immunodeficiency Virus (HIV) have a propensity to develop certain neoplastic diseases.[3] Conley et al showed a 16-fold increase in the development of vulvovaginal and perianal condylomata acuminata or intraepithelial neoplasia in a cohort of HIV-infected women compared with uninfected women.[4] Another series found that HIV-infected patients had a 3.3-fold increased risk of recurrent or persistent vulvar intraepithelial neoplasia after treatment compared with HIV-uninfected patients.[5]

CASE REPORT

A 29-year-old female patient presented to the dermatology department with a nonhealing ulcer on the vulva of 4 months duration. It was associated with severe itching and burning sensation. She also complained of loss of weight over 10 kg over 3 months. Her medical history revealed that she was a housewife married for 6 years with no extramarital exposure. The patient's known HIV-risk factor was her husband, who was reportedly HIV-positive. Physical examination revealed a moderately built women with an erythematous verrucous indurated growth measuring about 2 cm × 1 cm over the right side of labia majora, covered with dirty grayish-white precipitate [Figure 1]. There was no enlargement of lymph nodes and on careful examination rest of vagina and cervix were normal. Onychomycosis of fingernails and toenails were seen. CD4 count is 216 cells/mm 3 pap smear was normal and colposcopic examination of cervix and vagina were normal. Histopathology of the lesion from labia majora revealed focally invasive moderately differentiated SCC [Figures 2 and 3]. Her chest X-ray was found to be normal and computed tomography-abdomen revealed ill-defined soft tissue lesion in the vaginal region. Laboratory studies confirmed HIV. The patient was put on tenofovir, lamivudine, and efavirenz. The patient was in stage1 vulvar cancer, and she underwent modified radical vulvectomy with primary closure [Figure 4]. Postoperative recovery was uneventful, and no recurrence was seen over a follow-up period of 9 months.

Figure 1

Closer view of the verrucous growth

Figure 2

Low power - pointer shows malignant changes

Figure 3

High power - infiltration in squamous epithelium showing atypical cell with nuclear hyperchromasia, pleomorphism

Figure 4

After surgery modified radical vulvectomy with primary closure

DISCUSSION

According to National AIDS control organization HIV estimations 2012–2013, the estimated number of people living with HIV/AIDS in India were 20.89 lakhs (15–49 age group). Over the past 15 years, it has become widely accepted that there is an association between cervical disease and infection with the HIV.[67] Invasive cervical cancer was designated in 1993 as an AIDS case defining illness by the Centers for Disease Control and Prevention.[3] Since both cervical and vulvar cancers share certain risk factors, and invasive cervical cancer can occur simultaneously or metachronously with invasive vulvar cancer. A 23-fold risk increase for vulvar/vaginal cancer has been shown for people who have received organ transplants. Similarly, HIV-positive women appear to be an increased risk of vaginal cancer and precancer, though the magnitude of the increased risk varies in published papers from around 7 (vulvar and vaginal cancer combined) to 21 times higher.[8]

There are only nine reported cases of invasive vulvar cancer in HIV-seropositive women in the literature. Eight of the nine reported patients were younger than 40 years of age. The youngest patient reported was a 12-year-old with vertically acquired HIV infection.[9]

Carcinoma of the vulva is uncommon, and it is a disease of elderly women. Our study has demonstrated that invasive vulvar carcinoma is not uncommon in younger age group and this could be linked to immunosuppression. Vulvar cancer can occur independent of hormonal influence as there is no difference in binding capacity of estrogen receptors in normal, atrophic and malignant skin. Without properly functioning immune system tumor cells escape destruction and proliferate unchecked. The genetic factor control various factors such as individual susceptibility and ability to activate and deactivate carcinogens, to produce interferons, which may affect patient susceptibility to viral infections and malignancies and regulation of the immune system. Therefore, our patient developed invasive squamous cell cancer due to immunosuppression caused by HIV infection.[10] Management of invasive vulvar cancer in this young population needs to be balanced between appropriate curative surgery, which will often be radical, versus the desire to perform less mutilating surgery in young women. Treatment often depends on the stage of the disease. So we have opted for modified radical vulvectomy with primary closure.

With increasingly comprehensive care and more effective antiretroviral and antimicrobial therapies, HIV-infected patients with compromised immunity are now surviving for extended periods of time. We can expect that lower genital tract neoplasia is likely to become a more common presentation of HIV disease among infected women, and hence strategies need to be developed for early detection and treatment of anogenital neoplasia and invasive malignancies in the setting of HIV-induced immunodeficiency.

CONCLUSION

Due to the rarity of primary vulvar carcinoma, the clinical behavior of this neoplasm in the HIV-infected patient is poorly understood. Our case indicates that although vulvar carcinoma is a disease of the elderly, young women infected with HIV are predisposed to vulvar carcinoma. This should be considered as a serious condition in HIV-infected patients. Clinicians caring for HIV-infected women should be careful to routinely examine the vulva and perianal region and to biopsy any suspicious areas for early diagnosis and treatment to improve patients prognosis.

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Conflicts of interest

There are no conflicts of interest.