Abstract
Background
Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines.
Methods
In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012–2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models.
Results
Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9).
Conclusions
Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.
Keywords: anal cancer screening, human papillomavirus, women with human immunodeficiency virus
Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.
(See the Editorial Commentary by Clifford and Wei on pages 929–31.)
Human immunodeficiency virus (HIV)-induced immunosuppression greatly facilitates high-risk human papillomavirus (hrHPV) infection and carcinogenesis in the lower anogenital tract [1, 2]. Among women with HIV (WWH), the incidence of HPV-associated anal cancer is estimated to be 22 per 100 000 person-years, which is significantly elevated compared with the general population [3–5]. Although antiretroviral therapy can suppress HIV replication and restore immunity in most patients, its effect on reducing anal cancer has so far proven to be limited [6–8]. The Anal Cancer/HSIL Outcomes Research (ANCHOR) study has firmly demonstrated that treating anal high-grade squamous intraepithelial lesions (aHSIL; the putative precursor) prevents anal cancer in people with HIV [9]. Accordingly, anal cancer prevention through screening for and treatment of aHSIL should be promptly incorporated into the care for WWH [10].
Several professional associations recommend anal cytology screening for WWH with a history of cervical/vulvar HSIL or receptive anal intercourse; others readily extend such screening to all WWH [11–14]. The current practice is to refer women with abnormal anal cytology results (ie, atypical squamous cells of undetermined significance or worse, ASCUS or worse) to high-resolution anoscopy (HRA) examination and biopsy for histological diagnosis. Several proposed algorithms have incorporated hrHPV testing as a reflex test aiming to improve screening effectiveness [15, 16].
Accumulating evidence indicates that HPV-associated precancer and cancer at genital sites (ie, cervix, vagina, or vulva), even when treated successfully, increase the susceptibility to anal HPV disease [5]. Multizonal anogenital neoplasia has been well recognized in WWH [17]. A recent metanalysis reported that routine cervical cancer screening results, namely HPV status and cytohistopathology, predict anal HPV16 infection and aHSIL, and thus anal cancer risk [18]. Among HIV-related variables, low CD4 T-cell count (nadir and current) has been a statistically significant predictor of anal HPV16 and aHSIL; however, it is worth noting that aHSIL frequently occurs in women with controlled HIV viremia and restored CD4 T-cell counts [19, 20].
In this retrospective study of 381 WWH, we reported initial anal cytology screening and hrHPV testing results. A subset of participants with ASCUS or worse anal cytology underwent HRA and had histological diagnosis. We further analyzed demographics, HIV-related variables, and concurrent genital screening results with the aim of identifying independent predictors for the following outcomes: anal hrHPV infection, anal HPV16 infection, and histological aHSIL. The latter 2 outcomes have been considered as surrogate markers for anal cancer risk [18].
METHODS
Patient Selection
As part of a specialized women's health program in our HIV clinic, anal cytology screening and hrHPV cotesting were often conducted at the time of cervical cancer screening. After Institutional Review Board approval, we queried the Mount Sinai Data Warehouse from 2012 to 2019 for WWH with available data on initial anal cytology and hrHPV cotesting as well as genital (cervical or vaginal for women posthysterectomy) cotesting within 6 months. Electronic medical records were reviewed for age, race/ethnicity, history of smoking, HPV vaccination status, date of HIV diagnosis, nadir CD4 T-cell count, as well as HIV-1 RNA viral level, and CD4 T-cell count within 6 months of anal screening. History of cervical, vaginal, and vulvar HSIL and cancer was recorded.
Cytology Screening
Cervical cytological samples were collected from the cervical transformation zone with a cytobrush and an extended tip spatula. Vaginal cytological samples (n = 17) were obtained from the vaginal cuff for women status post total hysterectomy. Anal cytological samples were collected from the anal verge to the squamocolumnar junction using a cytobrush or polyester-tipped swab. Cytological samples were preserved in PreservCyt medium and ThinPrep slides were prepared. All diagnoses were rendered by cytopathologists from the Mount Sinai Hospital following the 2014 Bethesda System: unsatisfactory for evaluation, negative for intraepithelial lesion or malignancy (NILM), ASCUS, low-grade squamous intraepithelial lesion (LSIL), and HSIL [21].
High-Risk HPV Testing
A fluid aliquot of the genital or anal cytological sample was tested for HPV16, HPV18, and 12 other high-risk types (pooled results for HPV31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) using the Roche Cobas 4800 HPV assay (Roche Diagnostics). Results were classified into the following 3 categories: samples that tested positive for HPV16 were recorded as “HPV16”; those that tested negative for HPV16 but positive for HPV18 and/or the other high-risk types were recorded as “others”; and if none of the 14 types were detected, hrHPV status was recorded as “negative.”
High-Resolution Anoscopy and Biopsy
WWH with anal cytological diagnosis of ASCUS or worse were referred for HRA. HRA procedures were performed in an office setting following previously described techniques [22]. Briefly, the perianal area, anal canal, and squamocolumnar junction were treated with 5% acetic acid and Lugol's iodine and then visualized under a high-resolution colposcope at 15-fold magnification. Any areas with abnormal mucosal appearance suspicious for dysplasia or cancer were biopsied. Surgical pathologists at the Mount Sinai Hospital diagnosed all anal biopsies on hematoxylin and eosin slides following Lower Anogenital Squamous Terminology criteria [23]. p16 immunohistochemistry was used in approximately 30% of cases to facilitate a diagnosis. Histological diagnoses were classified for analysis as either HSIL or non-HSIL.
Statistical Analysis
Descriptive statistics was used to summarize the baseline characteristics of the study cohort. Anal hrHPV and HPV16 negative or positive groups were compared using χ2 test for categorical variables and using Kruskal-Wallis test for time since HIV diagnosis. Multivariable logistic regression models were used to identify independent predictors of anal hrHPV infection using the entire cohort (model 1), including variables such as age, race/ethnicity, smoking, HIV load, years living with HIV, nadir CD4 count, history of HPV vaccination, genital cytology, and genital hrHPV infection. Model 2 was used to identify predictors of anal HPV16 infection including all variables in model 1 and genital HPV16 infection. Predictors of histological aHSIL were analyzed for the subset of participants who underwent HRA-guided tissue biopsy. The first adjusted model included demographics, clinical variables and genital cytology, and genital hrHPV testing results (model 2). The second adjusted model included additional variables: anal cytology, anal hrHPV infection, and anal HPV16 infection (model 3). All analyses were conducted in STATA version 17.
RESULTS
Demographic and Clinical Characteristics
During 2012–2019, 381 WWH met the inclusion criteria. Table 1 details the cohort demographic and clinical characteristics. Median age was 49 years (range, 20–81 years). All participants were prescribed antiretroviral therapy.
Table 1.
Univariable Analyses of Characteristics Associated With Anal High-Risk HPV and HPV16 Infection (n = 381; Entire Study Cohort Except Where Noted)
| Characteristics | Anal High-Risk HPV | P | Anal HPV 16 | P | ||
|---|---|---|---|---|---|---|
| Negative (n = 149) | Positive (n = 232) | Negative (n = 332) | Positive (n = 49) | |||
| Age, y | ||||||
| ȃ≤ 40 (n = 91, 24%) | 37 (25) | 54 (23) | .73 | 79 (24) | 12 (24) | .92 |
| ȃ> 40 (n = 290, 76%) | 112 (75) | 178 (77) | 253 (76) | 37 (76) | ||
| Race/ethnicity (n = 321) | ||||||
| ȃHispanic (n = 120, 37%) | 53 (36) | 67 (29) | .43 | 103 (31) | 17 (35) | .20 |
| ȃBlack, NH (n = 179, 56%) | 69 (46) | 110 (47) | 160 (48) | 19 (39) | ||
| ȃWhite, NH (n = 22, 7%) | 8 (5) | 14 (6) | 17 (5) | 5 (10) | ||
| Time since HIV diagnosis, y, median (IQR) | 16 (10–23) | 16 (9.5–22) | .61 | 16 (10–22) | 17 (9–22) | .98 |
| Nadir CD4 T-cell count, cells/mm3 | ||||||
| ȃ≤ 200 (n = 197, 52%) | 56 (38) | 141 (61) | <.001 | 173 (52) | 24 (49) | .68 |
| ȃ> 200 (n = 184, 48%) | 93 (62) | 91 (39) | 159 (48) | 25 (51) | ||
| Current CD4 T-cell count, cells/mm3 | ||||||
| ȃ≤ 500 (n = 159, 42%) | 41 (28) | 118 (51) | <.001 | 135 (41) | 24 (49) | .27 |
| ȃ> 500 (n = 222, 58%) | 108 (72) | 114 (49) | 197 (59) | 25 (51) | ||
| HIV RNA viral load, copies/mL | ||||||
| ȃ≤ 50 (n = 246, 65%) | 113 (76) | 133 (57) | <.001 | 214 (64) | 32 (65) | .91 |
| ȃ> 50 (n = 135, 35%) | 36 (24) | 99 (43) | 118 (36) | 17 (35) | ||
| Smoking | ||||||
| ȃCurrent (n = 124, 32%) | 40 (27) | 84 (36) | .04 | 102 (31) | 22 (45) | .09 |
| ȃFormer (n = 117, 31%) | 43 (29) | 74 (32) | 102 (31) | 15 (31) | ||
| ȃNever (n = 140, 37%) | 66 (44) | 74 (32) | 128 (39) | 12 (24) | ||
| Human papillomavirus vaccine | ||||||
| ȃYes (n = 19, 5%) | 10 (7) | 9 (4) | .22 | 18 (5) | 1 (2) | .31 |
| ȃNo (n = 362, 95%) | 139 (93) | 223 (96) | 314 (95) | 48 (98) | ||
| Prior gynecological examination (n = 126) | ||||||
| ȃCervical or vulvar HSIL (n = 16, 13%) |
5 (14) | 11 (12) | .80 | 13 (12) | 3 (19) | .44 |
| Concurrent genital ASCUS or worse (n = 371, excluding 10 inadequate genital samples) | ||||||
| ȃYes (n = 100, 27%) | 18 (12) | 82 (36) | <.001 | 82 (25) | 18 (38) | .07 |
| ȃNo (n = 271, 73%) | 128 (88) | 143 (64) | 242 (75) | 29 (62) | ||
| Concurrent genital hrHPV | ||||||
| ȃYes (n = 114, 30%) | 14 (9) | 100 (43) | <.001 | 89 (27) | 25 (51) | .001 |
| ȃNo (n = 267, 70%) | 135 (91) | 132 (57) | 243 (73) | 24 (49) | ||
| Concurrent genital HPV16 | ||||||
| ȃYes (n = 16, 4%) | 4 (3) | 12 (5) | .24 | 7 (2) | 9 (18) | <.001 |
| ȃNo (n = 365, 96%) | 145 (97) | 220 (95) | 325 (98) | 40 (82) | ||
Data are No. (%) except where indicated.
Abbreviations: ASCUS, atypical squamous cells of undetermined significance; HIV, human immunodeficiency virus; HPV, human papillomavirus; hrHPV, high-risk HPV; HSIL, high-grade squamous intraepithelial lesion; IQR, interquartile range; NH, non-Hispanic.
Cytology
Forty-seven participants had inadequate cytological samples (39 anal and 10 genital samples, with 2 participants yielding both inadequate anal and genital samples). The remaining 334 participants with paired anal and genital cytological diagnoses were analyzed. Anal cytological diagnoses were NILM (n = 108, 32%), ASCUS (n = 144, 43%), LSIL (n = 53, 16%), and HSIL (n = 29, 9%). Genital cytological diagnoses were NILM (n = 240, 72%), ASCUS (n = 39, 12%), LSIL (n = 44, 13%), and HSIL (n = 11, 3%). As shown in Figure 1A, abnormal cytology rate (defined as ASCUS or worse) was significantly higher in anal than genital sites (68% vs 28%, P < .001). There was moderate concordance between the severity of anal and genital cytological diagnoses (Table 2).
Figure 1.
Anal and genital screening results. Data presented as percentage of participants in each category. A, Cytological diagnoses (n = 334, 47 participants with inadequate anal and/or genital samples were excluded). B, High-risk HPV testing results (n = 381). Categories (any high-risk HPV, HPV16, and others) are nonmutually exclusive events. Others are HPV18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. Abbreviations: ASCUS, atypical squamous cells of undetermined significance; HSIL, high-grade squamous intraepithelial lesion; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion or malignancy.
Table 2.
Concordance Between Paired Anal and Genital Cytological Diagnoses (n = 334, 47 Participants With Inadequate Anal and/or Genital Samples Are Excluded)
| Genital Cytological Diagnosis |
Anal Cytological Diagnosis | ||||
|---|---|---|---|---|---|
| Total | NILM | ASCUS | LSIL | HSIL | |
| Total | 334 | 108 (32) | 144 (43) | 53 (16) | 29 (9) |
| NILM | 240 (72) | 96 (40) | 103 (43) | 23 (10) | 18 (8) |
| ASCUS | 39 (12) | 6 (15) | 21 (54) | 7 (18) | 5 (13) |
| LSIL | 44 (13) | 5 (11) | 16 (36) | 19 (43) | 4 (9) |
| HSIL | 11 (3) | 1 (9) | 4 (36) | 4 (36) | 2 (18 |
Data are No. (%).
Cramer’s V = 0.22 (moderate association); P < .001.
Abbreviations: ASCUS, atypical squamous cells of undetermined significance; HSIL, high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; NILM, negative for intraepithelial lesion or malignancy.
High-Risk HPV Testing
High-risk HPV was detected in 246 (65%) participants at anal and/or genital sites. The remaining 135 (35%) tested negative at both sites. hrHPV and HPV16 prevalence was 61% and 13% in anus versus 30% and 4% in genital sites. As shown in Figure 1B, anus only hrHPV infection (35%) was the most common, followed by infection at both anogenital sites (26%) and genital only infection (4%). HPV16 infection showed a similar distribution: anus only (11%), both anogenital sites (2%), and genital only (2%).
Anal HRA and Biopsy
Among 167 participants with ASCUS or worse anal cytology, 126 (75%) underwent HRA examination and biopsy within 6 months. Histological aHSIL was detected in 53 participants (42%). The majority (n = 48, 91%) harbored 1 or 2 high-grade lesions. Five participants (9%) harbored 3 or 4 high-grade lesions. Concurrent genital cytological results for participants with aHSIL were inadequate (n = 1), benign (n = 36), ASCUS (n = 4), LSIL (n = 11), and HSIL (n = 1). Concurrent genital hrHPV testing results were negative (n = 29) or positive (n = 24), including HPV16 (n = 2).
Predictors for Anal Outcomes
Univariable analyses (Table 1) indicated that anal hrHPV infection was significantly associated with nadir CD4 T-cell count ≤ 200 cells/mm3, current CD4 T-cell count ≤ 500 cells/mm3, HIV RNA viral load > 50 copies/mL, ASCUS or worse genital cytology, and genital hrHPV infection (P < .001). Anal HPV16 infection was associated only with genital HPV16 infection (P < .001); other factors failed to show associations that reached statistical significance.
Table 3 lists independent predictors that were identified in multivariable adjusted models for anal hrHPV infection overall and HPV16 infection in particular. Other factors (age, race/ethnicity, smoking history, and years of HIV diagnosis) did not reach statistical significance (data not shown). Predictors of histological aHSIL were identified as genital hrHPV infection (using adjusted model excluding anal screening results) or anal HPV16 infection (using adjusted model including anal screening results).
Table 3.
Multivariable Adjusted Logistic Regression Models Predict Outcomes of Anal HPV Disease
| Outcome | Model Cohort | Independent Predictor | Proportion of Outcome With Risk Factor, % | Odds Ratio (95% CI) |
|---|---|---|---|---|
| Anal hrHPV infectiona | Entire cohort (n = 381) | Concurrent genital hrHPV infection | 43 | 5.05 (2.51–10.10) |
| Concurrent genital abnormal cytology | 35 | 1.88 (1.00–3.59) | ||
| Low nadir CD4 count | 61 | 1.97 (1.20–3.22) | ||
| Anal HPV16 infectionb | Entire cohort (n = 381) | Concurrent genital HPV16 infection | 18 | 9.52 (3.03–29.90) |
| Anal histological HSIL | HRA participants (n = 126) | Concurrent genital hrHPV infectionb | 45 | 2.78 (1.01–7.64) |
| Anal HPV16 infectionc | 36 | 10.9 (2.96–40.18) |
Abbreviations: CI, confidence interval; HPV, human papillomavirus; HRA, high-resolution anoscopy; hrHPV, high-risk HPV; HSIL, high-grade squamous intraepithelial lesion.
Model 1 includes variables such as age, race/ethnicity, smoking, HIV load, years with HIV, nadir CD4 count, history of HPV vaccination, genital cytology, and genital hrHPV infection.
Model 2 includes all variables in model 1 and genital HPV16 infection.
Model 3 includes all variables in model 2 and anal cytology, anal hrHPV infection, and anal HPV16 infection.
DISCUSSION
In this cross-sectional study of 381 WWH, we reported initial anal cytology screening and hrHPV testing results. Among them, 126 participants with ASCUS or worse anal cytology underwent HRA and received a histological diagnosis. The cohort primarily comprised women with longstanding HIV infection (median 16 years) and relatively robust HIV virologic suppression and immune restoration. The major findings are (1) anal HPV disease was more prevalent than genital HPV disease, (2) genital HPV16 infection was a strong independent predictor of anal HPV16 infection, and (3) anal HPV16 and genital hrHPV infection were strong independent predictors of histological aHSIL.
Our study is most comparable to the AIDS Malignancy Consortium (AMC) 084 study (n = 256 WWH) in terms of methodology and cohort characteristics [19, 24]. They reported slightly lower rates of anal hrHPV infection (48% vs 61% in our cohort) and abnormal anal cytology (59% vs 68% in our cohort). Their histological aHSIL rate was 27% of all participants, including those with normal anal cytology, which was higher than ours (14% of all participants). When limited to participants with ASCUS or worse cytology, the histological aHSIL rate was closely aligned between their study (37%) and ours (42%). Nonetheless, both studies revealed a substantial anal disease burden upon primary screening, providing a strong rationale for universal anal cancer screening in WWH.
In our cohort, genital hrHPV infection, HPV16 infection, and cytological abnormality were relatively less prevalent (30%, 4%, and 28%). Of note, HPV16 accounted for a larger proportion of anal infections than genital infections. While our lower genital disease burden could be partially attributed to prior screening and treatment, studies of WWH have consistently reported that anal HPV disease is at least comparable to, and often more prevalent than, genital disease [25, 26]. For instance, the SUN study of 120 WWH reported 85% anal and 70% cervical hrHPV infection as well as 38% anal and 33% cervical abnormal cytology [27]. The AMC 084 study reported 48% anal and 27% cervical hrHPV infection; and 59% anal and 29% cervical abnormal cytology [24]. The development of high HPV prevalence in the anal canal is multifactorial; one major contributor is its defective immune surveillance and HPV clearance, especially for the oncogenic types [28–30].
A recent meta-analysis on the age-specific prevalence of anogenital HPV infection described that there is a shift from predominant cervical HPV infection to anal infection among WWH around the age of 35 [31]. Participants in our study were relatively old with 76% of them above age 40 years, corresponding to the age group that has shifted from cervical to anal infection. Indeed, we found that isolated anal hrHPV infection was the most common manifestation in our cohort (35%), higher than coinfection of anogenital sites (26%) or isolated genital infection (4%). Notably, HPV16 infection followed the same pattern (11%, 2%, and 2%).
In a meta-analysis of 3352 WWH with paired cervical and anal findings, Lin et al concluded that anal cancer risk, measured by anal HPV16 positivity and HSIL diagnosis, could be stratified by cervical determinants such as hrHPV status, cytohistopathological diagnosis, and their combinations [18]. While the results of our adjusted analyses support their conclusions, genital HPV status appeared more statistically powerful in predicting anal disease than genital cytological diagnosis. In our models, genital hrHPV and HPV16 infection strongly predicted anal infection of the corresponding types (odds ratio [OR], 5.05 and 9.52). Genital hrHPV infection was also a significant, albeit weak, predictor of histological aHSIL (OR, 2.78). In contrast, genital abnormal cytology was only a weak predictor of anal hrHPV infection (OR, 1.88). Regardless, anal HPV16 infection proved to be the best predictor of histological aHSIL (OR, 10.9), a finding that has been well established in prior studies [32]. We therefore advocate that HPV genotyping should play a more pivotal role in anal cancer screening, particularly for WWH.
Nadir CD4 count ≤ 200 cells/mm3 in our analysis was a weak predictor of anal hrHPV infection (OR, 1.97) and not a predictor of anal HPV16 or histological aHSIL. Meanwhile, current CD4 count and HIV load were not predictive of any anal outcomes. Our results are in line with the meta-analysis, which found the HIV immunosuppression markers (eg, lower current CD4 cell count or higher current HIV load) are relatively weak determinants of anal HPV16 and HSIL in WWH [18]. Conversely, several clinical trials have associated low CD4 count with anal oncogenic HPV infection and aHSIL [19, 20, 33]. These inconsistent findings are likely due to the heterogeneity of study participants and irregularities in data collection. Whether HIV-related variables are relevant in clinical practice remains to be investigated.
It is vital to note that histological aHSILs frequently occur in WWH without significant genital findings. In our cohort, 49% of women with aHSIL revealed benign genital findings, including negative hrHPV. The AMC087 study reported a similar pattern: 25% of aHSIL cases had benign cervical cytology and 21.8% were negative for cervical hrHPV [19]. Likewise, the meta-analysis showed that 69% of HPV16-positive aHSIL cases had normal cervical cytology while 44% were negative for cervical hrHPV [31]. Clearly, WWH with normal genital findings still warrant additional screening for anal HPV disease.
Our study benefited from a large cohort of WWH who underwent both genital and anal cancer screening as part of our women's health program. Due to the retrospective nature, our analyses were limited by the fact that data collection was not standardized and certain risk factors were not routinely collected, such as history of receptive anal intercourse and prior gynecological diseases. HRA and biopsy were not performed for all participants but only for those with ASCUS or worse anal cytology, a fact that could introduce selective bias in our analyses.
In conclusion, we presented the primary anal cancer screening results from one of the largest WWH cohorts published to date. The high prevalence of anal hrHPV, HPV16, and precancerous lesions we observed fully corroborates the significant anal cancer risk among WWH. With emerging evidence provided by the ANCHOR study, all WWH should receive anal cancer screening and aHSIL treatment. While genital HPV diseases are predictive of anal disease, a substantial number of WWH develop isolated anal HPV disease, supporting universal anal screening regardless of history of genital HPV disease.
Contributor Information
Yuxin Liu, Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kevin Weiss, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Andrés Ramírez Zamudio, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Monica Prasad Hayes, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mona Saleh, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Michael M Gaisa, Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Keith Sigel, Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Notes
Financial support. This work was supported by the National Cancer Institute (grant number R01CA256660).
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