Human Papillomavirus–Associated Anogenital Pathology in Females With HPV‐Positive Oropharyngeal Squamous Cell Carcinoma

Abstract

We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogenital disease in women with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) via a retrospective cohort study with prospective contact to update history at Mayo Clinic in Rochester, Minnesota. Females undergoing treatment for nonmetastatic HPV-positive OPSCC from 2011 to 2019 were identified. Clinical history and outcomes were abstracted from medical records. Patients without documented anogenital history were contacted, consented, and administered a survey, and external records were requested and reviewed. Seventeen of 46 patients (37.0%) had a history of anogenital HPV-associated disease, and 16 of 17 (94.1%) required procedures to diagnose or treat HPV lesions. The cervix was the most common site (16/17, 94.1%). Procedures included colposcopy (n = 6), cervical excision (n = 3), cryotherapy (n = 4), and hysterectomy (n = 3). One case of fatal cervical carcinoma was noted, diagnosed 1 year following OPSCC. Three of 17 (17.6%) had HPV-related vulvovaginal disease, and 1 of 17 had anal disease. Patients with a history of HPV-positive OPSCC may be at elevated risk for HPV-associated anogenital disease.

Low Rates of Dual-Site and Concordant Oral-Cervical Human Papillomavirus Infections and Cancers: A Systematic Review

“…Among women with a primary diagnosis of oral cancer, the number of secondary cervical cancers was lowest among medical record-based studies ( 122 , 123 ), followed by provincial registries ( 121 , 127 ), and highest among national studies ( 112 , 113 , 117 , 120 , 126 ). National studies reported that the incidence of a secondary cervical cancer ranged from 4.5-192.5 per 10,000 women ( 112 , 113 , 117 , 120 , 126 ) ( Table 3C ).…”

“…Although we specifically included studies focused on HPV-related oral cancers, the sites of oral cancers varied across studies (e.g., some studies included oropharynx, oral cavity and pharynx, some only included oropharyngeal, and some vaguely defined HPV-related head and neck sites). Five studies examined the risk of a secondary cervical cancer after a primary diagnosis of oral cancer ( 113 , 120 – 123 ). Half of the studies (n=11/22, 50%) examined the risk of a secondary oral cancer diagnosis after a primary diagnosis of a cervical cancer (n=6) ( 106 – 108 , 111 , 115 , 116 ) or a cervical intraepithelial neoplasia (CIN) (n=5) ( 109 , 110 , 118 , 124 , 125 ).…”

“…Six studies investigated the risk of a secondary cervical and/or oral cancer after a primary diagnosis of an oral and/or cervical cancer ( 112 , 114 , 117 , 119 , 126 , 127 ). Most studies utilized data from country or state level cancer registries to monitor disease surveillance (n=15/22, 68%) ( 106 – 118 , 124 , 126 ); three studies conducted medical chart reviews ( 120 , 121 , 123 ); four studies collected at least some data from institutional or provincial tumor registries ( 119 , 122 , 125 , 127 ).…”

“…In addition, few studies randomly selected participants for inclusion from a comprehensive list of the target population (n=26, 23%) ( 18 , 21 , 24 , 32 , 34 , 36 , 37 , 44 , 45 , 83 , 92 , 104 , 108 , 109 , 111 – 113 , 115 – 119 , 121 , 124 , 126 , 127 ). This contributed to most studies being classified as ‘moderate’ for selection bias (n=99, 87%) ( 4 , 15 – 26 , 28 – 33 , 35 – 43 , 46 – 49 , 51 – 58 , 60 – 77 , 79 – 82 , 84 – 91 , 93 – 103 , 105 – 107 , 109 – 116 , 118 – 123 , 125 ). For data collection within synchronous and asynchronous HPV testing studies, some studies did not specify an HPV infection sample collection method, so the validity and reliability were unknown or they relied on self-reported HPV infections (n=10/92, 11%) ( 4 , 33 , 40 , 55 , 63 , 64 , 73 , 94 , 99 , 101 ).…”

Current Therapeutic Strategies in Patients with Oropharyngeal Squamous Cell Carcinoma: Impact of the Tumor HPV Status

“…It is considered to be one of the leading causes of death in patients that have been cured from their primary OPSCC [19]. The HPV oncogenic properties at other cancer sites and in particular the anogenital organs are well demonstrated [35,36]. In this regard, in a recent study investigating sequential acquisition of HPV infection between genital and oral anatomic sites in males, Dickey et al showed that the Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7-3.1) and 3.5 (95% CI: 1.9-6.4) for oral to genital infection [35].…”