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Preinvasive and invasive cervical neoplasia in patients with HIV infection

Preinvasive and invasive cervical neoplasia in patients with HIV infection
Author:
William R Robinson, MD
Section Editors:
Barbara Goff, MD
David M Aboulafia, MD
Deputy Editors:
Alana Chakrabarti, MD
Sadhna R Vora, MD
Literature review current through: Jan 2024.
This topic last updated: Jul 27, 2023.

INTRODUCTION — Patients with HIV infection have higher rates of preinvasive (ie, cervical intraepithelial neoplasia [CIN]) and invasive cervical neoplasia compared with patients without HIV infection. In 1993, the Centers for Disease Control and Prevention (CDC) designated moderate and severe CIN as a condition of early symptomatic HIV infection and invasive cervical cancer as an AIDS-defining condition; since that time, cervical cancer has become one of the most common AIDS-related malignancies. Furthermore, patients with HIV and cervical cancer are at a higher risk for overall mortality than patients without HIV and cervical cancer.

Specific issues regarding preinvasive and invasive cervical neoplasia in patients with HIV infection are reviewed here. Screening for cervical cancer and the evaluation of abnormal screening results in patients with HIV infection, as well as other related issues, are reviewed separately.

●(See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states".)

●(See "Screening for cervical cancer in resource-limited settings".)

●(See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)

●(See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention".)

●(See "HIV infection and malignancy: Epidemiology and pathogenesis".)

INCIDENCE — The incidence of histologically proven CIN is four to five times higher among patients with HIV infection compared with patients without HIV infection or adolescents with high-risk sexual behaviors [1-3]. In a prospective cohort study including over 650 patients with no evidence of CIN by Papanicolaou (Pap) test or colposcopy at study entry, patients with HIV (328 patients; mean CD4 count of 429 cells/microL) compared with patients without HIV (325 patients) were more likely to develop biopsy-confirmed CIN (20 versus 5 percent; incidence 8.3 versus 1.8 cases per 100 person-years) over the 30-month follow-up period [3]. Of the CIN lesions, almost 90 percent were low-grade lesions and no invasive cancers were noted.

Similarly, the risk of cervical cancer among patients with HIV is higher compared with patients without HIV [4-9]. In one retrospective study including over 62,000 patients with cervical cancer from 1996 to 2016, patients with HIV (609 patients) compared with patients without HIV had a higher incidence of squamous cell carcinoma (incidence ratio: 3.7, 95% CI 3.3-3.9) and adenocarcinoma (incidence ratio: 1.5, 95% CI 1-2.1) [10].

PATHOGENESIS — As with patients without HIV, in patients with HIV, infection of the female genital tract with human papillomavirus (HPV) is generally felt to be necessary, but not sufficient, for the development of cervical cancer, as only a small percentage of patients infected with HPV develop cervical cancer. Major factors in pathogenesis, including viral subtype, older age, and duration of infection, are discussed in detail separately. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Pathogenesis'.)

In patients with HIV, immunosuppression is a key factor in pathogenesis, as a weakened response of the immune system allows persistence of the HPV infection. This is supported by the observation that patients with low CD4 cell counts (eg, CD4 count <200 cells/microL):

●Have the highest prevalence of HPV infection [11,12].

●More commonly harbor high-risk HPV types [11,12].

●Are at high risk for persistence of cervical HPV infection [11-13]. Some data suggest that HPV infection is likely to recur after a latent phase in patients with HIV, which is rarely seen in other patients [14].

The degree of immunosuppression in patients with HIV predicts both the occurrence and severity of cervical disease [15-18]. In a multicenter series of 485 patients with HIV, those with CD4 counts <200 compared with >500 cells/microL had a twofold increase in CIN and a lower rate of regression of untreated low-grade disease [17]. Subsequently, a case-control series of patients with HIV noted that those diagnosed with invasive cervical cancer had lower median CD4 counts and higher median HIV viral loads than those without cervical cancer [18].

ROLE OF HPV VACCINATION — A history of cervical dysplasia or genital warts is not a contraindication to vaccination. In fact, in patients without HIV and a history of human papillomavirus (HPV) disease, HPV vaccination has been shown to provide protection against future infection from HPV types not already acquired and has been associated with a lower rate of CIN recurrence [19,20]. Although this has not been formally demonstrated among patients with HIV, it is likely also true in this setting, particularly given that many patients with HIV have a high rate of HPV coinfection [21]. (See "Cervical intraepithelial neoplasia: Management", section on 'HPV vaccination in patients with CIN'.)

HPV vaccination in patients with HIV without CIN is discussed elsewhere. (See "Human papillomavirus vaccination", section on 'Patients with HIV or immunocompromising conditions'.)

CLINICAL PRESENTATION — Presentation of cervical cancer in patients with HIV is similar to that of patients without HIV and discussed in detail separately. (See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

In patients with HIV, however, cervical carcinoma tends to be more advanced at diagnosis, and patients are frequently more debilitated [22,23]. Metastases are common and may occur at unexpected sites [23,24]. Some patients with cervical cancer are diagnosed while hospitalized for other manifestations of AIDS. Since some symptoms of AIDS are similar to those of advanced cancer (eg, weight loss, fatigue, and lymphadenopathy), the presence of cervical cancer may be masked.

MANAGEMENT OF PREINVASIVE DISEASE — The appropriate management of patients with HIV and CIN, including optimal therapy with excision or ablation, role of postablative treatment with topical agents, and timing and method of follow-up, is largely unknown. Close follow-up by a provider with experience in HIV-related cervical disease is essential.

CIN 1 — In general, management (with observation or treatment [ie, excision or ablation]) of patients with CIN 1 and HIV is the same as patients without HIV infection and depends on the preceding cytology result (eg, low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL]) and age of the patient. We follow the American Society for Colposcopy and Cervical Pathology (ASCCP) consensus guidelines for the management of patients without HIV. This is described in detail separately. (See "Cervical intraepithelial neoplasia: Management", section on 'Management of patients ≥25 years' and "Cervical intraepithelial neoplasia: Management", section on 'Management of patients <25 years'.)

CIN 1 is a low-grade lesion with at least one-third of patients with HIV showing regression [17,25]. Antiretroviral therapy (ART) is associated with increased rates of regression and decreased rates of recurrence in patients with HIV [26,27]. This is discussed in more detail below. (See 'Antiretroviral therapy' below.)

The risk of progression in patients with HIV is less clear. In two prospective studies including patients with HIV and CIN 1, progression occurred in 4 to 7 percent of patients [28,29]; other studies have reported higher rates [26,30-32], and progression can occur rapidly [33]. However, given this uncertainty and lack of data to define patient subgroups at higher or lower risk of progression, it is reasonable to follow the ASCCP guidelines for patients without HIV infection.

CIN 2,3

Excision or ablation — In general, management of CIN 2,3 is the same for patients with and without HIV infection; when treatment is performed (ie, all CIN 3 lesions, most CIN 2 lesions), excision with either loop electrosurgical excision procedure (LEEP; also called large loop excision of the transformation zone) or cold knife conization is performed; excision has largely replaced the practice of ablation. Hysterectomy is occasionally performed instead of excision or ablation (eg, patient preference, additional gynecologic pathology such as symptomatic uterine fibroids) but is unacceptable as a primary treatment for CIN in most instances. The choice between excision and ablation is discussed in detail elsewhere and is the same in patients with HIV as in patients without HIV. (See "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and prognosis and follow-up after treatment".)

While success rates for these approaches in patients without HIV is over 90 percent [34], success rates are lower in patients with HIV. Persistence and recurrence of CIN after treatment have been reported in approximately 20 to 60 percent of patients with HIV [35-40]; recurrence rates also may be higher in patients undergoing cryotherapy compared with excision. Thus, for most patients with HIV, we suggest excision over ablation.

In a randomized trial comparing cryotherapy with LEEP for treatment of CIN 2,3 in 400 patients with HIV in Kenya, cryotherapy resulted in a higher rate of recurrence over two years (30 versus 19 percent, relative risk 1.7, 95% CI 1.1-2.7) [40]. Adverse events occurred in 20 percent of patients in the cryotherapy group (45 events, including change in pathology and death due to other causes) and in 15 percent of the LEEP group (38 events, including change in pathology and unrelated gynecologic complications). In a secondary analysis of this trial, clearance of high-risk HPV subtypes was higher in the LEEP compared with cryotherapy group (hazard ratio 1.4, 95% CI 1-1.9) during the 24-month study period [41].

Factors contributing to poorer treatment outcomes in patients with HIV include:

●Incomplete excision or ablation of CIN – In two studies of LEEP, CIN was found at the margins in all (11 of 11) tissue specimens of patients with HIV but in only 32 percent (86 of 265) of tissue specimens from patients without HIV [42,43]. It is not known why positive margins occurred more often among patients with HIV. In remaining at the margins, recurrence was more likely in patients with HIV compared with patients without HIV.

●Immunosuppression – In two reports, recurrence in patients with HIV was more common in patients with a CD4 count below 500/microL (45 versus 18 percent and 61 versus 20 percent) [36,37].

Role of medical therapy — Because results of standard excisional therapy are better in patients without versus with HIV, use of primary or adjuvant medical therapy to improve treatment outcomes in patients with HIV have been investigated. While little or no effect has been seen with oral beta-carotene [44,45], isotretinoin [46], or systemic or intralesional interferon [47,48], other agents may have some benefits and are described here.

Topical fluorouracil — Topical fluorouracil (FU) may be used as adjunctive therapy to excision/ablation procedures for CIN 2,3 [49,50], but we do not routinely use this in our practice. While there may be a reduction in the recurrence risk of CIN associated with the use of 5-FU, toxicity (eg, moderate-to-severe inflammation of the vulva and vagina) often limits its use.

The value of topical FU in patients with HIV was illustrated in a phase III trial supported by the AIDS Clinical Trials Group (ACTG 200) [49]. In this trial including 101 patients with HIV and previously treated CIN 2 or CIN 3, patients receiving six months of prophylaxis with FU (topical application of 2 g of 5% cream biweekly) compared with no treatment had reduced recurrence rates of any CIN (28 versus 47 percent) and high-grade lesions (8 versus 31 percent) on cervical cytology and colposcopy during the 18-month follow-up period. Patients in the FU-treatment group were more likely to experience at least one adverse effect (eg, abnormal bleeding, irritation, discharge) compared with the no-treatment group (32 versus 20 percent, respectively). A subsequent randomized trial including patients without HIV and histologically proven CIN 2,3 treated with 5-FU prior to their excisional procedure showed adverse events, though mild, occurred in the majority of patients (>70 percent) [51]. (See "Cervical intraepithelial neoplasia: Management", section on 'Investigational therapies'.)

Antiretroviral therapy — ART is associated with improvement in CD4 counts and reductions in HIV viral load; improvements in these measures are also associated with a lower risk of CIN and cervical cancer [11,13]. This indirectly suggests that ART may reduce the incidence and recurrence of CIN in patients with HIV. ART also appears to be associated with regression of CIN [27].

Studies of the effect of ART on CIN are limited and conflicting because of small numbers of study participants and differences in study design [17,26,27,52-57]. The highest quality data come from a large, multicenter prospective cohort study by the Women's Interagency HIV Study Group which suggests that the benefit of ART is due, at least in part, to improvement in CD4 counts [27]. In this study including 312 patients with HIV and newly diagnosed CIN (the majority of whom [96 percent] had LSILs), rates of CIN regression were compared before and after initiating ART. Major findings from this study include:

●No incident CIN lesions regressed before the initiation of ART.

●After initiation of ART, overall regression rate was 12.5 percent (95% CI 9.9-15.1) per year, with the incidence of regression increasing over time. Among the 312 patients, 45 percent had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. By contrast, regression to normal cytology occurred in 16 of 27 (59 percent) patients without HIV.

●A higher rate of regression in patients with HIV taking ART was observed in patients with higher CD4 counts (336 versus 230 cells/microL) and low-grade incident CIN.

A subsequent prospective cohort study showed similar results [58]. In this study including 537 patients with HIV, there was a trend toward CIN regression in patients on ART compared with patients not taking ART, although this did not reach statistical significance. In addition, patients with CIN who did versus did not take ART were more likely to show clearance of HPV infection (high and low risk subtypes; hazard ratio 4.5, 95% CI 1.2-16.3); this effect was not seen in patients with normal or atypical squamous cells of undetermined significance cervical cytology.

Another study suggested that adherence to and effectiveness of ART regimens is associated with a reduced burden of HPV infection and squamous intraepithelial lesions (SILs). In this report, 286 patients with HIV were prescribed ART and followed prospectively. Those who used ART >95 percent of the time and those who had effective suppression of HIV replication had significantly decreased prevalence of new HPV infections, as well as increased clearance of existing SILs [59].

The use of ART to improve the prognosis in patients with HIV and reduce the incidence of other neoplastic complications of AIDS is discussed separately. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "HIV infection and malignancy: Epidemiology and pathogenesis".)

Follow-up — In general, follow-up of CIN is more frequent in patients with HIV compared with patients without HIV (see "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and prognosis and follow-up after treatment", section on 'Follow-up after treatment' and "Cervical intraepithelial neoplasia: Management"); however, there is no consensus regarding the best approach and no formal guidelines exist.

In our practice, we recommend follow-up with both cervical cytology (with or without human papillomavirus [HPV] testing) and colposcopy (with liberal use of biopsy) at intervals of no longer than three months for an indefinite period. For patients for whom access to health care or follow-up testing is limited, the threshold for management may be lower (eg, hysterectomy rather than repeat cytology and colposcopy in a postmenopausal patient). (See 'Patients with poorly controlled HIV' below.)

Patients with HIV infection and CIN should be advised that recurrence is more frequent than in the general population and the risk of recurrence correlates with the degree of immunosuppression [36-38,60]. Recurrence rates are as high as 56 percent and up to 87 percent in severely immunocompromised (CD4 lymphocyte count <200 cells/microL) patients [1,38,61]. Use of the various testing methods (ie, cytology, co-testing, routine colposcopy) is discussed in detail separately. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Rationale and evidence for screening methods'.)

Furthermore, cancer can develop rapidly in patients with HIV. A large study matching AIDS and cancer registries found that the average interval between diagnosis of CIN and development of invasive disease was considerably shorter in patients with HIV than in HIV-negative patients (3.2 versus 15.7 years, respectively) [4]. However, these data were largely obtained before widespread use of ART.

Long-term data on lower genital tract neoplasia in patients with HIV are limited. While it has been reported that multiple concurrent HPV-associated neoplasia may not be uncommon in patients with HIV, even in those whose disease is well controlled as measured by CD4 and viral loads [62], the same authors previously found that the overall outcomes were similar to those seen in patients not infected with HIV in the same population with 20-year follow-up [63].

MANAGEMENT OF INVASIVE CANCER

Overview — Standard therapy for invasive cervical cancer consists of surgery and/or chemoradiation therapy, irrespective of whether patients have HIV. (See "Management of early-stage cervical cancer" and "Management of locally advanced cervical cancer".)

Surgical excision is most appropriate for early-stage disease, with adjuvant chemoradiation administered for those at intermediate or high risk of recurrence, as in patients without HIV. (See "Management of early-stage cervical cancer", section on 'Adjuvant therapy'.)

Primary chemoradiation (without surgery) is used in patients with locally advanced disease, again, in similar fashion as in patients without HIV. (See "Management of locally advanced cervical cancer", section on 'Primary chemoradiation'.)

Finally, chemotherapy alone is reserved for palliation.

Therapy of invasive cervical cancer in patients with HIV infection must take into consideration several additional factors:

●Patients with HIV-associated cervical cancer are usually younger than patients without HIV.

●In most patients (26 of 28 in one report), invasive cervical cancer is the initial AIDS-defining diagnosis [64].

●Patients with HIV and cervical cancer tend to be less immunosuppressed (as assessed by the CD4 count) than patients with HIV and other AIDS-defining illnesses [65].

●The introduction of antiretroviral therapy (ART) did not decrease the incidence of invasive cervical cancer in the United States to the same degree as other malignancies associated with HIV infection (eg, Kaposi sarcoma, central nervous system non-Hodgkin lymphoma) [66]. This is because cervical cancer, unlike Kaposi sarcoma, was not a rare disease prior to the AIDS era and the vast majority of American patients with cervical cancer are not infected with HIV. Therefore, any reduction in risk of cervical neoplasia in patients with HIV had a minimal impact on the overall incidence of cervical cancer (see "HIV infection and malignancy: Epidemiology and pathogenesis"). However, ART may have a positive impact on prognosis [67]. (See 'Antiretroviral therapy' above.)

Based on these observations, aggressive therapy should be offered to most patients with HIV with cervical cancer. The patient should be informed that the prognosis in general is worse than in patients without HIV infection (table 1), although this information is derived largely from patients not on ART, and that prognosis associated with concomitant antiviral therapy is not known. Some patients will be unwilling to tolerate the side effects associated with aggressive therapy if there is only a small chance of survival.

Early-stage cervical cancer

Surgery — As with patients without HIV, surgery is typically performed for patients with HIV and early-stage cervical cancer (ie, International Federation of Gynecology and Obstetrics [FIGO] stage IA, IB1, and IB2; (table 2 and table 3)). The choice of procedure varies with the clinical setting:

●Local excision by cold knife conization or loop electrosurgical excision procedure (LEEP) may be adequate for microinvasive lesions (<3 mm depth of invasion) in patients who wish to maintain fertility. If future fertility is not an issue, simple hysterectomy is preferred. (See "Cervical intraepithelial neoplasia: Diagnostic excisional procedures".)

●Modified radical or radical hysterectomy is appropriate for grossly visible tumors that are confined to the cervix (up to and including stage IB2).

This is discussed in more detail separately. (See "Management of early-stage cervical cancer", section on 'Type of surgery'.)

Advantages of surgery over radiation in such patients include preservation of ovarian function and decreased rates of sexual dysfunction (see "Management of early-stage cervical cancer", section on 'Adverse effects'). Although there is an increase in early morbidity with surgery (eg, anesthesia, blood loss, infection), overall morbidity from elective gynecology surgery does not appear to be increased in otherwise asymptomatic patients with HIV [68].

The addition of postoperative chemoradiotherapy should be considered for patients at increased risk of recurrent or persistent disease. (See "Management of early-stage cervical cancer", section on 'Indications'.)

Locally advanced cervical cancer

Chemoradiation — Chemoradiation with curative intent is the preferred approach in locally advanced cervical cancer, irrespective of whether patients have HIV. (See "Management of locally advanced cervical cancer", section on 'Radiation therapy'.)

The major advantage of a nonsurgical approach compared with surgical therapy for cervical cancer is less immediate morbidity.

However, pelvic chemoradiation in patients with HIV is not without adverse effects. Recovery from myelosuppression in immunosuppressed patients is, in general, typically slower than in immunocompetent patients, and as such, it may be slower in patients with versus without HIV. Depending on its severity, temporary cessation of therapy may be required. It is not known if pelvic chemoradiation therapy can potentiate the immunosuppressive effects of HIV infection.

Radiation proctitis is a potential complication of pelvic radiation that may be exacerbated by concomitant chemotherapy. It is usually treated symptomatically and, if available, topical butyrate enemas may accelerate healing [69]. If this is ineffective, radiation and chemotherapy should be withheld until the diarrhea resolves. (See "Radiation proctitis: Clinical manifestations, diagnosis, and management".)

The diarrhea must be distinguished from other forms of diarrhea associated with HIV infection (see "Evaluation of the patient with HIV and diarrhea"). Late complications of pelvic chemoradiotherapy, such as bowel obstruction and bowel and bladder fistulas, are uncommon.

Metastatic cervical cancer

Chemotherapy — Chemotherapy alone can provide palliative benefit for patients with cervical cancer. The combination of cisplatin, paclitaxel, and bevacizumab has been shown to improve survival in patients with advanced or metastatic cervical cancer, and is considered the standard regimen for patients, irrespective of HIV infection [70]. (See "Management of recurrent or metastatic cervical cancer".)

There are limited data concerning the efficacy of chemotherapy in advanced cervical cancer in patients with HIV; a significant tumor response appears to be rare [24].

SPECIAL CONSIDERATIONS

Patients with poorly controlled HIV — For patients in whom HIV is poorly controlled (ie, high viral loads), who are unable to adhere to antiretroviral therapy (ART), have persistently low CD4 counts, or limited access to health care, the threshold for management of CIN may be lower and shorter follow-up intervals may be used. However, there is no standard management, largely because of the variability in presentation of these patients. In addition, priority is often given to optimizing the HIV infection (eg, restarting ART) and management of other acute conditions related to HIV, rather than treating CIN.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cervical cancer screening, prevention, and management".)

SUMMARY AND RECOMMENDATIONS

●Clinical importance – Patients with HIV infection have higher rates of preinvasive (ie, cervical intraepithelial neoplasia [CIN]) and invasive cervical neoplasia compared with patients without HIV infection. Patients with HIV and cervical cancer are also at a higher risk for overall mortality than patients without HIV and cervical cancer. (See 'Introduction' above.)

●Pathogenesis and prevention – Infection with human papillomavirus (HPV) and the degree of immunosuppression (eg, CD4 count <200 cells/microL) are thought to be key factors for both the occurrence and severity of cervical disease. A history of CIN or genital warts is not a contraindication to HPV vaccination. (See 'Pathogenesis' above and 'Role of HPV vaccination' above.)

●Role of antiretroviral therapy – Use of antiretroviral therapy in patients with HIV is associated with a lower risk of CIN and cervical cancer. (See 'Antiretroviral therapy' above.)

●Preinvasive disease

•Management – In general, management of patients with preinvasive disease (ie, CIN 1, 2, or 3) and HIV is the same as patients without HIV infection and we follow the American Society for Colposcopy and Cervical Pathology (ASCCP) consensus guidelines for the management of patients without HIV. (See "Cervical intraepithelial neoplasia: Management".)

-For patients with CIN 1 or CIN 2, either excision or observation is performed, depending on the preceding cytology result (eg, low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL]) and the age of the patient. (See 'CIN 1' above and 'CIN 2,3' above.)

-For patients with CIN 3, treatment is indicated. (See 'CIN 2,3' above.)

-When treatment is performed for CIN 1, 2, or 3, we perform excision rather than cryoablation. Excision is typically performed by loop electrosurgical excision procedure (LEEP). (See 'Excision or ablation' above.)

•Follow-up – Patients with HIV should be counseled that recurrence is more frequent than in the general population. As a result, in our practice, we monitor with both cervical cytology (with or without HPV testing) and colposcopy (with liberal use of biopsy) at intervals of no longer than three months for an indefinite period. (See 'Follow-up' above.)

●Invasive cancer

•Standard therapy for invasive cervical cancer consists of surgery and/or chemoradiation therapy, irrespective of whether patients have HIV (see "Management of early-stage cervical cancer" and "Management of locally advanced cervical cancer"):

-For patients with early-stage disease, we perform surgical excision. For such patients with intermediate or high risk of recurrence, adjuvant chemoradiation is administered. (See "Management of early-stage cervical cancer", section on 'Adjuvant therapy'.)

-For patients with locally advanced disease, primary chemoradiation (without surgery) is used. (See "Management of locally advanced cervical cancer", section on 'Primary chemoradiation'.)

-For patients with metastatic disease as well as those who are not candidates for a local treatment approach, we administer chemotherapy. (See "Management of recurrent or metastatic cervical cancer".)

●Patients with poorly controlled HIV – For patients in whom HIV is poorly controlled (ie, high viral loads), are unable to adhere to antiretroviral therapy (ART), or have persistently low CD4 counts, the threshold for management of CIN may be lower and shorter follow-up intervals may be used. Priority is often given to optimizing the HIV infection (eg, restarting ART) and management of other acute conditions related to HIV. (See 'Patients with poorly controlled HIV' above.)

  1. Wright TC Jr, Ellerbrock TV, Chiasson MA, et al. Cervical intraepithelial neoplasia in women infected with human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. New York Cervical Disease Study. Obstet Gynecol 1994; 84:591.
  2. Moscicki AB, Ellenberg JH, Crowley-Nowick P, et al. Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents. J Infect Dis 2004; 190:1413.
  3. Ellerbrock TV, Chiasson MA, Bush TJ, et al. Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA 2000; 283:1031.
  4. Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000; 92:1500.
  5. Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 2005; 97:425.
  6. Franceschi S, Dal Maso L, Arniani S, et al. Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons with AIDS in Italy. Cancer and AIDS Registry Linkage Study. Br J Cancer 1998; 78:966.
  7. Serraino D, Carrieri P, Pradier C, et al. Risk of invasive cervical cancer among women with, or at risk for, HIV infection. Int J Cancer 1999; 82:334.
  8. Serraino D, Dal Maso L, La Vecchia C, Franceschi S. Invasive cervical cancer as an AIDS-defining illness in Europe. AIDS 2002; 16:781.
  9. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370:59.
  10. Rositch AF, Levinson K, Suneja G, et al. Epidemiology of Cervical Adenocarcinoma and Squamous Cell Carcinoma Among Women Living With Human Immunodeficiency Virus Compared With the General Population in the United States. Clin Infect Dis 2022; 74:814.
  11. Palefsky JM, Minkoff H, Kalish LA, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst 1999; 91:226.
  12. Denny L, Boa R, Williamson AL, et al. Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women. Obstet Gynecol 2008; 111:1380.
  13. Ahdieh L, Muñoz A, Vlahov D, et al. Cervical neoplasia and repeated positivity of human papillomavirus infection in human immunodeficiency virus-seropositive and -seronegative women. Am J Epidemiol 2000; 151:1148.
  14. Theiler RN, Farr SL, Karon JM, et al. High-risk human papillomavirus reactivation in human immunodeficiency virus-infected women: risk factors for cervical viral shedding. Obstet Gynecol 2010; 115:1150.
  15. Maiman M, Tarricone N, Vieira J, et al. Colposcopic evaluation of human immunodeficiency virus-seropositive women. Obstet Gynecol 1991; 78:84.
  16. Schäfer A, Friedmann W, Mielke M, et al. The increased frequency of cervical dysplasia-neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression. Am J Obstet Gynecol 1991; 164:593.
  17. Delmas MC, Larsen C, van Benthem B, et al. Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women. AIDS 2000; 14:1775.
  18. Leitao MM Jr, White P, Cracchiolo B. Cervical cancer in patients infected with the human immunodeficiency virus. Cancer 2008; 112:2683.
  19. Centers for Disease Control and Prevention (CDC). FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010; 59:626.
  20. Lichter K, Krause D, Xu J, et al. Adjuvant Human Papillomavirus Vaccine to Reduce Recurrent Cervical Dysplasia in Unvaccinated Women: A Systematic Review and Meta-analysis. Obstet Gynecol 2020; 135:1070.
  21. Palefsky JM, Gillison ML, Strickler HD. Chapter 16: HPV vaccines in immunocompromised women and men. Vaccine 2006; 24 Suppl 3:S3/140.
  22. Maiman M, Fruchter RG, Guy L, et al. Human immunodeficiency virus infection and invasive cervical carcinoma. Cancer 1993; 71:402.
  23. Schwartz LB, Carcangiu ML, Bradham L, Schwartz PE. Rapidly progressive squamous cell carcinoma of the cervix coexisting with human immunodeficiency virus infection: clinical opinion. Gynecol Oncol 1991; 41:255.
  24. Singh GS, Aikins JK, Deger R, et al. Metastatic cervical cancer and pelvic inflammatory disease in an AIDS patient. Gynecol Oncol 1994; 54:372.
  25. Belafsky P, Clark RA, Kissinger P, Torres J. Natural history of low-grade squamous intraepithelial lesions in women infected with human immunodeficiency virus. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11:511.
  26. Robinson WR, Hamilton CA, Michaels SH, Kissinger P. Effect of excisional therapy and highly active antiretroviral therapy on cervical intraepithelial neoplasia in women infected with human immunodeficiency virus. Am J Obstet Gynecol 2001; 184:538.
  27. Ahdieh-Grant L, Li R, Levine AM, et al. Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women. J Natl Cancer Inst 2004; 96:1070.
  28. Massad LS, Evans CT, Minkoff H, et al. Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus. Obstet Gynecol 2004; 104:1077.
  29. Del Mistro A, Bertorelle R, Franzetti M, et al. Antiretroviral therapy and the clinical evolution of human papillomavirus-associated genital lesions in HIV-positive women. Clin Infect Dis 2004; 38:737.
  30. Robinson WR, Luck MB, Kendall MA, Darragh TM. The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: a substudy of a randomized, phase III chemoprevention trial. Am J Obstet Gynecol 2003; 188:896.
  31. Melnikow J, Nuovo J, Willan AR, et al. Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol 1998; 92:727.
  32. Massad LS, Schneider M, Watts H, et al. Correlating Papanicolaou Smear, Colposcopic Impression, and Biopsy: Results from the Women's Interagency HIV Study. J Low Genit Tract Dis 2001; 5:212.
  33. Holcomb K, Maiman M, Dimaio T, Gates J. Rapid progression to invasive cervix cancer in a woman infected with the human immunodeficiency virus. Obstet Gynecol 1998; 91:848.
  34. Burghardt E, Holzer E. Treatment of carcinoma in situ: evaluation of 1609 cases. Obstet Gynecol 1980; 55:539.
  35. Heard I, Bergeron C, Jeannel D, et al. Papanicolaou smears in human immunodeficiency virus-seropositive women during follow-up. Obstet Gynecol 1995; 86:749.
  36. Maiman M, Fruchter RG, Serur E, et al. Recurrent cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women. Obstet Gynecol 1993; 82:170.
  37. Wright TC Jr, Koulos J, Schnoll F, et al. Cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus: outcome after loop electrosurgical excision. Gynecol Oncol 1994; 55:253.
  38. Fruchter RG, Maiman M, Sedlis A, et al. Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus. Obstet Gynecol 1996; 87:338.
  39. Reimers LL, Sotardi S, Daniel D, et al. Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women. Gynecol Oncol 2010; 119:92.
  40. Greene SA, De Vuyst H, John-Stewart GC, et al. Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial. JAMA 2019; 322:1570.
  41. Chung MH, De Vuyst H, Greene SA, et al. Human Papillomavirus Persistence and Association With Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy vs Loop Electrosurgical Excision Procedure Among HIV-Positive Women: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol 2021; 7:1514.
  42. Robinson WR, Tirpack JS. The predictive value of LEEP specimens with involved margins for residual dysplasia. Int J Gynecol Cancer 1996; 6:140.
  43. Robinson WR, Lund ED, Adams J. The predictive value of LEEP specimen margin status for residual/recurrent cervical intraepithelial neoplasia. Int J Gynecol Oncol 1998; 8:109.
  44. Mackerras D, Irwig L, Simpson JM, et al. Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Br J Cancer 1999; 79:1448.
  45. Romney SL, Ho GY, Palan PR, et al. Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection. Gynecol Oncol 1997; 65:483.
  46. Robinson WR, Andersen J, Darragh TM, et al. Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women. Obstet Gynecol 2002; 99:777.
  47. Frost L, Skajaa K, Hvidman LE, et al. No effect of intralesional injection of interferon on moderate cervical intraepithelial neoplasia. Br J Obstet Gynaecol 1990; 97:626.
  48. Yliskoski M, Syrjänen K, Syrjänen S, et al. Systemic alpha-interferon (Wellferon) treatment of genital human papillomavirus (HPV) type 6, 11, 16, and 18 infections: double-blind, placebo-controlled trial. Gynecol Oncol 1991; 43:55.
  49. Maiman M, Watts DH, Andersen J, et al. Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial. Obstet Gynecol 1999; 94:954.
  50. Sillman FH, Sedlis A. Anogenital papillomavirus infection and neoplasia in immunodeficient women. Obstet Gynecol Clin North Am 1987; 14:537.
  51. Fonseca BO, Possati-Resende JC, Salcedo MP, et al. Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix: A Randomized Controlled Trial. Obstet Gynecol 2021; 137:1043.
  52. Heard I, Schmitz V, Costagliola D, et al. Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy. AIDS 1998; 12:1459.
  53. Heard I, Tassie JM, Kazatchkine MD, Orth G. Highly active antiretroviral therapy enhances regression of cervical intraepithelial neoplasia in HIV-seropositive women. AIDS 2002; 16:1799.
  54. Minkoff H, Ahdieh L, Massad LS, et al. The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women. AIDS 2001; 15:2157.
  55. Orlando G, Fasolo MM, Schiavini M, et al. Role of highly active antiretroviral therapy in human papillomavirus-induced genital dysplasia in HIV-1-infected patients. AIDS 1999; 13:424.
  56. Lillo FB, Ferrari D, Veglia F, et al. Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy. J Infect Dis 2001; 184:547.
  57. Schuman P, Ohmit SE, Klein RS, et al. Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. J Infect Dis 2003; 188:128.
  58. Paramsothy P, Jamieson DJ, Heilig CM, et al. The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology. Obstet Gynecol 2009; 113:26.
  59. Gravitt PE, Kirk GD. Progress and pitfalls in defining the influence of highly active antiretroviral therapy on human papillomavirus-associated cervical disease. J Infect Dis 2010; 201:650.
  60. Gilles C, Manigart Y, Konopnicki D, et al. Management and outcome of cervical intraepithelial neoplasia lesions: a study of matched cases according to HIV status. Gynecol Oncol 2005; 96:112.
  61. Heard I, Potard V, Foulot H, et al. High rate of recurrence of cervical intraepithelial neoplasia after surgery in HIV-positive women. J Acquir Immune Defic Syndr 2005; 39:412.
  62. Davis K, Rogg K, Robinson WR. The Incidence and Management of Human Papilloma Virus-Associated Malignancies in Immunocompetent Human Immunodeficiency Virus-Infected Women. Gynecol Oncol 2019.
  63. Robinson WR. Long-Term Follow-Up of HIV-Infected Women with Cervical Dysplasia. AIDS Patient Care STDS 2015; 29:517.
  64. Maiman M, Fruchter RG, Clark M, et al. Cervical cancer as an AIDS-defining illness. Obstet Gynecol 1997; 89:76.
  65. Klevens RM, Fleming PL, Mays MA, Frey R. Characteristics of women with AIDS and invasive cervical cancer. Obstet Gynecol 1996; 88:269.
  66. International Collaboration on HIV and Cancer. Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 2000; 92:1823.
  67. Robinson WR, Freeman D. Improved outcome of cervical neoplasia in HIV-infected women in the era of highly active antiretroviral therapy. AIDS Patient Care STDS 2002; 16:61.
  68. Devito JR, Robinson WR. Gynecological surgical outcomes among asymptomatic human immunodeficiency virus-infected women and uninfected control subjects. J La State Med Soc 1995; 147:109.
  69. Vernia P, Fracasso PL, Casale V, et al. Topical butyrate for acute radiation proctitis: randomised, crossover trial. Lancet 2000; 356:1232.
  70. Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 2017; 390:1654.
Topic 3245 Version 34.0

References

1 : Cervical intraepithelial neoplasia in women infected with human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. New York Cervical Disease Study.

2 : Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents.

3 : Incidence of cervical squamous intraepithelial lesions in HIV-infected women.

4 : Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

5 : Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy.

6 : Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons with AIDS in Italy. Cancer and AIDS Registry Linkage Study.

7 : Risk of invasive cervical cancer among women with, or at risk for, HIV infection.

8 : Invasive cervical cancer as an AIDS-defining illness in Europe.

9 : Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.

10 : Epidemiology of Cervical Adenocarcinoma and Squamous Cell Carcinoma Among Women Living With Human Immunodeficiency Virus Compared With the General Population in the United States.

11 : Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women.

12 : Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women.

13 : Cervical neoplasia and repeated positivity of human papillomavirus infection in human immunodeficiency virus-seropositive and -seronegative women.

14 : High-risk human papillomavirus reactivation in human immunodeficiency virus-infected women: risk factors for cervical viral shedding.

15 : Colposcopic evaluation of human immunodeficiency virus-seropositive women.

16 : The increased frequency of cervical dysplasia-neoplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression.

17 : Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

18 : Cervical cancer in patients infected with the human immunodeficiency virus.

19 : FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP).

20 : Adjuvant Human Papillomavirus Vaccine to Reduce Recurrent Cervical Dysplasia in Unvaccinated Women: A Systematic Review and Meta-analysis.

21 : Chapter 16: HPV vaccines in immunocompromised women and men.

22 : Human immunodeficiency virus infection and invasive cervical carcinoma.

23 : Rapidly progressive squamous cell carcinoma of the cervix coexisting with human immunodeficiency virus infection: clinical opinion.

24 : Metastatic cervical cancer and pelvic inflammatory disease in an AIDS patient.

25 : Natural history of low-grade squamous intraepithelial lesions in women infected with human immunodeficiency virus.

26 : Effect of excisional therapy and highly active antiretroviral therapy on cervical intraepithelial neoplasia in women infected with human immunodeficiency virus.

27 : Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women.

28 : Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus.

29 : Antiretroviral therapy and the clinical evolution of human papillomavirus-associated genital lesions in HIV-positive women.

30 : The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: a substudy of a randomized, phase III chemoprevention trial.

31 : Natural history of cervical squamous intraepithelial lesions: a meta-analysis.

32 : Correlating Papanicolaou Smear, Colposcopic Impression, and Biopsy: Results from the Women's Interagency HIV Study.

33 : Rapid progression to invasive cervix cancer in a woman infected with the human immunodeficiency virus.

34 : Treatment of carcinoma in situ: evaluation of 1609 cases.

35 : Papanicolaou smears in human immunodeficiency virus-seropositive women during follow-up.

36 : Recurrent cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women.

37 : Cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus: outcome after loop electrosurgical excision.

38 : Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus.

39 : Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women.

40 : Effect of Cryotherapy vs Loop Electrosurgical Excision Procedure on Cervical Disease Recurrence Among Women With HIV and High-Grade Cervical Lesions in Kenya: A Randomized Clinical Trial.

41 : Human Papillomavirus Persistence and Association With Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy vs Loop Electrosurgical Excision Procedure Among HIV-Positive Women: A Secondary Analysis of a Randomized Clinical Trial.

42 : The predictive value of LEEP specimens with involved margins for residual dysplasia

43 : The predictive value of LEEP specimen margin status for residual/recurrent cervical intraepithelial neoplasia

44 : Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities.

45 : Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection.

46 : Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women.

47 : No effect of intralesional injection of interferon on moderate cervical intraepithelial neoplasia.

48 : Systemic alpha-interferon (Wellferon) treatment of genital human papillomavirus (HPV) type 6, 11, 16, and 18 infections: double-blind, placebo-controlled trial.

49 : Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial.

50 : Anogenital papillomavirus infection and neoplasia in immunodeficient women.

51 : Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix: A Randomized Controlled Trial.

52 : Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy.

53 : Highly active antiretroviral therapy enhances regression of cervical intraepithelial neoplasia in HIV-seropositive women.

54 : The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women.

55 : Role of highly active antiretroviral therapy in human papillomavirus-induced genital dysplasia in HIV-1-infected patients.

56 : Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy.

57 : Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women.

58 : The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology.

59 : Progress and pitfalls in defining the influence of highly active antiretroviral therapy on human papillomavirus-associated cervical disease.

60 : Management and outcome of cervical intraepithelial neoplasia lesions: a study of matched cases according to HIV status.

61 : High rate of recurrence of cervical intraepithelial neoplasia after surgery in HIV-positive women.

62 : The Incidence and Management of Human Papilloma Virus-Associated Malignancies in Immunocompetent Human Immunodeficiency Virus-Infected Women

63 : Long-Term Follow-Up of HIV-Infected Women with Cervical Dysplasia.

64 : Cervical cancer as an AIDS-defining illness.

65 : Characteristics of women with AIDS and invasive cervical cancer.

66 : Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults.

67 : Improved outcome of cervical neoplasia in HIV-infected women in the era of highly active antiretroviral therapy.

68 : Gynecological surgical outcomes among asymptomatic human immunodeficiency virus-infected women and uninfected control subjects.

69 : Topical butyrate for acute radiation proctitis: randomised, crossover trial.

70 : Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240).

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