What is oral cancer, the condition John Farnham is being treated for?

Seventy three-year-old Australian music icon John Farnham is in a stable condition in intensive care after undergoing surgery to remove an oral cancer. Farnham’s family paid tribute to the health-care professionals after more than 11 hours of surgery on Tuesday.

Original Article

Farnham’s diagnosis comes as a shock to many, there is little public awareness about oral cancer and the broader range of head and neck cancers. 

So what is it? Who is more likely to be diagnosed with it? And what does recovery or rehabilitation look like? 

Oral cancer is one type of head and neck cancer. While we can’t comment on Farnham’s condition specifically, we’re speech pathologists and researchers with experience working with our teams to support other patients with these cancers and guiding them through their recovery. 

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What is head and neck cancer? How common is it?

Head and neck cancers most commonly begin in the cells lining the mouth (oral cavity), nose and sinuses, throat (pharynx) or voice box (larynx). 

Risk factors for head and neck cancer include smoking, excessive alcohol consumption, and being infected with the human papillomavirus (HPV). But some patients may have no identifiable cause for their cancer. 

In Australia, almost 4,000 people are diagnosed with head and neck cancer each year, and this number is increasing

Globally, the impact of head and neck cancer disproportionately affects those in developing countries due to increased risk factors, delays in diagnosis and limitations on interventions. 

Cancers of the head and neck have typically been more common in men over the age of 65. However, an increase in cancers related to infection with HPV, the most common sexually transmitted infection, has seen a change in these demographics to include younger people. 


Read more: Health Check: can sex affect your risk of getting cancer?


Unfortunately, these cancers do not always receive the same media and philanthropic attention as other cancers.

What are the symptoms and treatments?

Finding cancer early is important but unfortunately, there are no formal screening tests for head and neck cancer.

Common signs and symptoms can include a neck lump, a lump or sore that does not heal, a red or white patch in the mouth, trouble speaking or using your voice, or difficulty breathing. Always speak to your doctor and dentist about any of these concerns.

Treatment for head and neck cancers can include surgical interventions, radiation therapy and/or chemotherapy. This will depend on the size, location, and progression of the cancer, among other factors. 

Treatment may include the insertion of a breathing tube (tracheostomy) or feeding tube (nasogastric or percutaneous endoscopic gastrostomy). For some these are temporary measures while recovering from surgery, for others they can be life-long changes. 

Breathing tubes impact and change the person’s ability to speak, cough and swallow. Feeding tubes can support the person’s nutritional needs. Changes to communication and swallowing may mean the person has difficulty with everyday activities such as eating a meal with family and singing their favourite songs. 

Survivorship is high, meaning people are living longer with the impacts of their cancer and its treatment. In 2006–2010, the five-year relative survival was 68% for all head and neck cancers combined.

What are the lasting effects?

Living with head and neck cancer may have big impacts on the physical, emotional, and social wellbeing of the person and their family.

At various stages of recovery, people who have had head and neck cancer can experience life-altering consequences, including pain and difficulties speaking, eating, drinking, swallowing and breathing. Their appearance may change after oral or facial reconstruction.

Older woman holds her throat
The cancer and its treatment can have major impacts on quality of life. Shutterstock

Survivors experience varying degrees of disease severity and feelings of distress. One survivor described her experience of head and neck cancer as “brutal,” saying “we lose our careers […] our relationships fall apart.” 

Examining social media posts on #headandneckcancer highlights others are concerned about fatigue, appearance, weight and nutrition. 

Families also feel the impact, with many experiencing elevated levels of distress and reduced quality of life.

Reducing stigma

Some of the risk factors for head and neck cancers such as smoking and heavy drinking are seen as “lifestyle risk factors” and may attract stigma. This can have a significant impact on recovery. 

Stigma increases distress, depression, anxiety and reduces social participation. These impacts are exacerbated for those who live in the public eye or are professional voice-users such as singers, radio broadcasters or teachers.


Read more: ‘It’s your fault you got cancer’: the blame game that doesn’t help anyone


Supporting loved ones after head and neck cancer

People with head and neck cancers require specialist, interdisciplinary health care. Multidisciplinary care teams include medical, nursing, and allied health professionals (speech pathologists, physiotherapists, dietitians, and occupational therapists) who work collaboratively to optimise the person’s health and rehabilitation

Original Article

Survivors also need strong social support, as changes in facial appearance and difficulties speaking and eating can lead to feelings of isolation, frustration, and a loss of enjoyment in social situations. Seeking psychological and emotional support is invaluable.

When communicating with a person with head and neck cancer, allow extra time for them to speak, maintain eye contact, minimise background noise and use body language and gesture to convey messages. 

Farnham’s family acknowledge a “long road of recovery and healing”. We wish our much-loved Farnsey a pathway through cancer that is enriched with love and support of family, friends, community and music.

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Diagnose HPV-driven oropharyngeal cancer

Accuracy of high-risk HPV DNA PCR, p16(INK4a)immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal cancer

Original Article

Abstract

Background

The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.

Methods

The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a)immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.

Results

Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.

Conclusions

Single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.

Peer Review reports

Background

In high-resource countries, human papillomavirus (HPV)-driven head and neck squamous cell carcinoma represents an increasing health problem, particularly in cancers of the oropharyngeal region, including base of tongue and tonsils [1,2,3,4]. An estimated 20–40% of oropharyngeal cancers (OPC) is believed to be caused by HPV infection, and the large majority of them (> 80%) are due to HPV16 [25]. Patients with HPV-induced cancers respond better to treatment and consequently have better survival than patients with HPV-unrelated OPC [6,7,8,9,10,11]. HPV-positive tumours, compared to the HPV-negative ones, are characterized by multiple molecular and clinic-pathological differences [12], which should be further investigated. These considerations highlight the importance of reliable and accurate markers, or marker combinations, to diagnose truly HPV-induced OPC and guiding patients’ risk-stratification.

The most widely applied detection method was based on PCR amplification of viral DNA to determine HPV-positivity. However, several independent studies have highlighted that PCR-based assays for the detection of HPV DNA are not sufficiently accurate to establish the viral causality [13,14,15,16,17]. These PCR-based methods are highly sensitive and can detect even a few DNA copies per sample, which might yield false-positive results mainly reflecting transient infections [18,19,20]. Additional markers, such as the presence of viral E6/E7 mRNA transcripts and p16(INK4a) expression as surrogates for HPV-induced transformation, allow a more accurate classification of HPV-driven head and neck cancers (HNC) [1521,22,23,24,25].

Nowadays, HPV E6/E7 oncogene transcript detection is considered the gold standard, for HPV-induced malignancies particularly depend on the carcinogenic potential of the HPV E6 and E7 oncoproteins [2326]. Nevertheless, viral transcript detection is laborious and may not be feasible everywhere in daily lab routine. This is particularly true for the detection of mRNA transcripts in formalin-fixed, paraffin-embedded (FFPE) tissue specimens, which are commonly used during routine diagnostic work up; however, RNA integrity may be affected by the fixation protocol.

HPV E7 oncogenic signaling brings about substantial overexpression of the cellular protein p16(INK4a) in HPV-transformed cells [27]. Therefore, the immunohistochemical detection of p16(INK4a) overexpression is presently applied as a surrogate biomarker of HPV-transformed cervical epithelium [28,29,30]. Similarly, p16(INK4a) immunohistochemistry (IHC) is regularly used to establish HPV association in HNC [222331,32,33]. Apart from single p16(INK4a) IHC, combined p16(INK4a) and HPV DNA detection by PCR is oftenly used.

HPV-AHEAD (FP7 funded network)

The HPV-AHEAD study (“Role of human papillomavirus infection and other co-factors in the aetiology of head and neck cancer in Europe and India”) group comprised partners from six European countries and from India (website HPV-AHEAD: https://hpv-ahead.iarc.fr/). The main goal of the study was to perform a comprehensive analysis on a large number of HNC cases to clarify pathogenic pathways in HNC carcinogenesis, and to identify clinically useful biomarkers.

In a previous publication [34], the results of the histological and molecular assessment of 1039 archived HNC specimens from Belgian patients were described, primarily using the detection of HPV DNA, mRNA, and p16(INK4a) IHC. In this study, we focus on the accuracy of these tests—individually and in combination—to diagnose hrHPV-driven oropharyngeal cancer.

Methods

Patient selection, clinical information and tissue specimen collection for the Belgian cohort

The overall study included patients with oropharyngeal, oral cavity, laryngeal, hypopharyngeal, and unspecified head and neck squamous cell carcinoma. For a detailed description of the patient characteristics, we refer to the previous publication of the Belgian HPV-AHEAD study data [34]. For the analyses in this study, the focus was on the oropharyngeal cancers [ICD-O-3 codes: C01 (base of tongue); C02.4 (lingual tonsil); C05.1 (soft palate); C05.2 (uvula); C09 (tonsil): C09.0, C09.1, C09.8 and C09.9; C10 (oropharynx): C10.0–10.4, C10.8 and C10.9].

FFPE tumour blocks and clinical information were collected from OPC patients treated in two Belgian hospitals (GZA and UZA), diagnosed between 1980 and 2010.

Ethical clearance was obtained from the Ethical Committees of ‘GZA hospitals’ (ref nb: BVDE/hp/2013/01.147), ‘UZA & UA (University of Antwerp)’ (ref nb: 11/47/362) and IARC, Lyon, France (ref nb: 11–30).

Preparation of tissue sections (University of Antwerp, Antwerp, Belgium)

FFPE-tissue blocks were all processed at the UA laboratory of cell biology and histology, following the optimized HPV-AHEAD sectioning protocol [3435]. Briefly, minimal ten sections (S) were prepared from each FFPE block. The first (S1) and the last (S10) 5 µm sections were hematoxylin and eosin (H&E) stained for morphologic histology interpretation and used to check for the presence of tumour. S2 and S9 (5 µm) were used for p16(INK4a) IHC staining, while the 10 µm sections S3–5 and S6–8 were used for the extraction of RNA and DNA, respectively.

Histological review

All sections were re-evaluated by the HPV-AHEAD pathology review panel. The review was blinded with respect to the original local diagnosis. Only FFPE blocks where S1 and S10 H&E sections reflected squamous tumour tissue were included in the analysis [34].

HPV E6*I mRNA analysis (DKFZ, Heidelberg, Germany)

All OPC cases were analysed for the presence of: (i) HPV16 E6*I mRNA, and (ii) ubiquitin C (ubC) mRNA as a cellular mRNA positive control (housekeeping gene used for RNA quality control). OPC cases positive for DNA of a non-HPV16 genotype were additionally analysed for E6*I mRNA of the respective genotype. Specimens that were HPV E6*I and/or ubC mRNA-positive (RNA+) were considered RNA valid. Reverse Transcription-PCR was carried out using the QuantiTect Virus Kit (Qiagen, Hilden, Germany), as described in full in former HPV-AHEAD publications [3436]. The type-specific E6*I mRNA assays identifying transcripts of fourteen high-risk and six possible/probable high-risk HPV genotypes [37] were applied.

HPV DNA genotyping (IARC, Lyon, France)

HPV DNA genotypes were detected by a E7 type-specific multiplex genotyping (E7-MPG) assay, which combines multiplex PCR and bead-based Luminex technology (Luminex Corporation, Austin, TX), as previously described [3839]. Type specific-MPG uses HPV type-specific primers targeting the E7 region of thirteen high-risk and six possible/probable high-risk HPV genotypes (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68a and b, 70, 73 and 82), as well as two low-risk HPV genotypes (HPV 6 and 11). Two primers for amplification of the beta-globin (β-globin) gene were also included to control for the DNA quality of each specimen. A detailed description of the DNA extraction and further HPV genotyping test characteristics can be found in the previous publication on the Belgian HPV-AHEAD study [34]. Genotyping controls and DNA preparation were blindly analysed, and no sign of contamination of negative controls was detected during the laboratory work.

p16(INK4a) expression (Roche mtm laboratories, Mannheim, Germany)

Expression of p16(INK4a) was evaluated by IHC, with a dual-immunostaining protocol for the simultaneous immunostaining of both p16(INK4a) and Ki-67 biomarkers (CINtec PLUS kit, Roche mtm laboratories AG, Mannheim, Germany), as previously described in the HPV-AHEAD publications [3436]. As in all HPV-AHEAD studies [343640], a continuous, diffuse staining for p16(INK4a) within the cancer area of the tissue sections was considered as positive, while a focal staining or no staining was considered negative. IHC slides were analysed without knowledge of any other clinical information (including HPV DNA and RNA status) by the scientists RR or DH and reviewed by one of the European members of the HPV-AHEAD pathology review panel (JPB, BLR, or FM). Discrepant cases were re-evaluated by a pathologist outside the review panel (AC), and final classification of the staining was based on majority consensus results.

Corresponding to the former Belgian HPV-AHEAD publication [34], the p16 slides with technical issues were restained and re-evaluated, to minimize the number of missing results.

Statistical analysis

Presence of viral mRNA was considered as the reference indicating HPV etiology. The accuracy of three possible test strategies was analysed: (a) hrHPV DNA PCR alone, (b) p16(INK4a) IHC alone, and (c) the combination of p16(INK4a) IHC and hrHPV DNA PCR; where positivity is defined by a co-positive result with both tests, a negative result by a co-negative result for both tests, and a discordant result by only one test being positive and the other being negative. Test strategy (c) involves three algorithms: ALGORITHM 1 (p16 + DNA) consists of p16(INK4a) IHC and hrHPV DNA PCR on all samples; ALGORITHM 2 (p16 → DNA) involves p16(INK4a) staining of all samples, followed by the HPV DNA test only on the p16(INK4a)-positive samples; ALGORITHM 3 (DNA → p16) involves HPV DNA PCR on all samples, followed by p16(INK4a) staining only on the HPV DNA-positive samples.

Sensitivity was defined as the proportion of test positive samples among HPV RNA-positive patients. Specificity was defined as the proportion of negative test results among HPV RNA-negative patients. Relative sensitivity and specificity of each test compared to the other tests were also assessed. Binomial 95% confidence intervals (95% CIs) were computed for proportions. Given the matched testing of the same patient specimens, McNemar 95% CIs were computed for relative accuracy parameters. Continuous variables were summarized by their mean and 95% CIs. ANOVA was used to compare mean age by gender.

Statistical analyses were performed using STATA 16 (StataCorp, College Station, TX). p-values were two sided and statistical significance was set at p equal or less than 0.05.

Results

Study population characteristics

Ninety-nine of 116 OPC patients were included in the analysis, after exclusions based on the pathology review (for reasons of not being a squamous cell carcinoma or not reflecting invasive cancer, N = 13) and beta-globin PCR negativity (N = 4). 71.7% (71/99) of the patients were male, 26.3% (26/99) were female, and for the remaining two samples the gender of the patients was not specified. The mean age at diagnosis was 67.3 years (95% CI 64.9–69.7) and was not different between males and females (p = 0.47).

HPV prevalence in OPC cases

HPV prevalence was determined by HPV DNA PCR, p16(INK4a) IHC, E6*I mRNA, and all combinations of tests in the HPV-AHEAD study. Out of 99 OPC cases, 36.4% (36/99) contained HPV DNA, 34.0% (33/97) showed p16(INK4a) positivity, and 28.9% (28/97) were HPV RNA-positive (Table 1). Twenty-six of the 28 HPV RNA-positive samples were positive for HPV16 (92.9%), the remaining 2 samples contained HPV18 (7.1%).Table 1 Prevalence of HPV determined by HPV DNA PCR (DNA), p16(INK4a)IHC (p16), E6*I mRNA (RNA), and all combinations of tests, in oropharyngeal cancer

Full size table

The proportion of HPV-positive OPCs varied between 28.4% (27/95) and 28.9% (28/97) for all combinations of tests that included RNA testing (DNA + RNA, p16 + RNA, DNA + p16 + RNA). For the combination of testing for HPV DNA and p16(INK4a) IHC, the overall prevalence was slightly higher (30.9%, 30/97).

Absolute and relative accuracy in the oropharynx and its subsites

Both absolute and relative accuracy of hrHPV DNA detection by PCR (hrHPV DNA), p16(INK4a) IHC (p16), and combined p16(INK4a) and DNA testing algorithms (p16 + DNA, p16 → DNA and DNA → p16), to identify a transforming HPV infection were calculated. In the following tables, only the results are shown for the samples that had valid results on all three tests performed (N = 95).

All RNA-positive OPC cases were positive for hrHPV DNA (100%, 28/28), in contrast to one out of 28 HPV RNA-positive samples that did not have a positive p16(INK4a) result (3.6%). Five out of 67 RNA-negative cases showed hrHPV DNA-positivity (7.5%), the same as observed for p16(INK4a) IHC. This number would be further lowered to only 2 positive cases out of 67 RNA-negatives (3.0%), if hrHPV DNA and p16(INK4a) testing (p16 + DNA) were combined. The same holds for the other algorithms where all samples would initially be tested on p16(INK4a) (p16 → DNA) or hrHPV DNA (DNA → p16), followed by the other test if the initial test result turned out positive. Data are detailed in Table 2, for all OPC cases, and for the tonsils and the base of tongue in specific. As the number of samples from other oropharyngeal subsites was very low, no relevant data can be shown.Table 2 hrHPV DNA, p16(INK4a) (p16) and combined hrHPV DNA/p16(INK4a)test results by hrHPV RNA status in cancers of the oropharynx, tonsils and base of the tongue

Full size table

The accuracy of hrHPV DNA PCR and p16(INK4a) IHC to detect a transforming HPV infection in OPCs was calculated (Table 3). Highest sensitivity (100.0%, 28/28) was noted for hrHPV DNA testing, while specificity was equal for both hrHPV DNA and p16(INK4a) (92.5%, 62/67). The best compromise was found in the combined testing of hrHPV DNA PCR and p16(INK4a)staining, with 96.4% (27/28) sensitivity and 97.0% (65/67) specificity. When looking in more detail to the proposed algorithms, all provided equal accuracy, however, with a 60% reduction in the number of HPV DNA PCR or p16(INK4a) IHC tests needed in the sequential testing algorithms.Table 3 Absolute sensitivity and specificity of hrHPV DNA PCR (hrHPV DNA), p16(INK4a) IHC (p16) and the combined testing (p16 + DNA) to identify a HPV-driven oropharyngeal cancer

Full size table

For the subgroup of the tonsils, p16(INK4a) staining alone was as sensitive (94.7%, 18/19) and specific (91.3%, 21/23) as the combined testing, in contrast to the base of tongue group, where all tests were 100% sensitive and specific, except for the p16(INK4a) specificity (85.7%, 12/14).

hrHPV DNA PCR testing was slightly more sensitive compared to p16(INK4a) IHC (ratio: 1.04, 95% CI 0.97–1.11), but equally specific (ratio: 1.00, 95% CI not computable) (see Table 4 and Additional file 1: Table S1). The combination of hrHPV DNA and p16(INK4a) was slightly more specific (ratio: 1.05, 95% CI 0.97–1.21) compared to both single tests.Table 4 Relative sensitivity and specificity of hrHPV DNA PCR (DNA) vs p16(INK4a) IHC (p16), and of DNA and p16(INK4a) vs combined testing (p16 + DNA), to identify a HPV-driven oropharyngeal cancer

Full size table

Discussion

In these Belgian OPC patients, PCR testing for HPV DNA showed 36% positive cases. This proportion lies somewhere between other published results from different parts of the world. Castellsagué et al. found a considerably lower prevalence of HPV DNA: 24.9% in OPC, in a large international series of 3,680 HNC biopsies [33]. A very similar proportion of HPV DNA-positive oropharyngeal squamous cell carcinoma of 35.6% was found by Kreimer et al. [19]. However, the meta-analysis of Ndiaye et al. showed a substantially higher prevalence up to 45.8% in OPC [17]. This worldwide overall prevalence is largely influenced by the very high prevalence in North America (60.4%), while the overall prevalence in Europe lands at 41.4%. The differences can probably be explained, in part, by the differences in the geographic origin of the samples, as well as the high heterogeneity in laboratory procedures and assays used in the various studies.

Due to its high sensitivity, HPV DNA PCR-based assays can detect low viral copy numbers, which may not trigger carcinogenesis. These assays cannot distinguish between transcriptionally-active and passenger HPV infections. Therefore, other assays (HPV E6*I mRNA, and p16(INK4a) staining) were evaluated to assess whether combined testing could improve the specificity. Only 28% of the samples with a valid HPV E6*I mRNA result were positive for HPV DNA and p16(INK4a), which might be the fraction of oropharyngeal cancers caused by HPV. After all, the detection of HPV E6 and/or E7 mRNA is seen as the gold standard in this context, because HPV-driven carcinomas critically depend on the continuous expression of E6/E7 oncogenes of hrHPVs [232641]. However, the detection of viral transcripts is challenging, not only because the RNA extraction step is laborious and time consuming, but specific infrastructures and equipment are needed. Therefore, HPV RNA assays may not be routinely feasible in all laboratories or on all tissue samples.

HPV-driven OPC represents an increasing health problem, and therefore, reliable and accurate diagnosis becomes essential. In our Belgian HPV-AHEAD study, HPV DNA PCR testing alone was 100% sensitive, but less specific (92.5%) compared to mRNA testing. The inherent strength of the PCR-based methodology lies in its capacity to detect very small amounts of HPV DNA. At the same time, strict laboratory procedures and controls are critical in reducing contamination-related false-positive findings [42]. Immunohistochemistry for p16(INK4a) is most widely used as a surrogate marker for hrHPV infection in FFPE tissues, also for oropharyngeal squamous cell carcinoma. p16(INK4a) IHC testing alone was a bit less sensitive (96.4%), but co-presence of hrHPV DNA and p16(INK4a) positivity was similarly sensitive (96.4%) and more specific (97.0%) compared to each test separately. In literature, several authors have advocated against the use of either p16(INK4a) or hrHPV DNA alone as indicators of HPV-induced etiology in cancers, but recommended their combined use as a reliable and practical approach to differentiate HPV-induced from HPV-unrelated tumours [2643,44,45]. The meta-analysis performed by Prigge et al. [46] also showed a similarly high (pooled) sensitivity of the combined testing (93%) and either p16(INK4a) (94%) or HPV DNA (98%) alone, and the (pooled) specificity (96%) was significantly higher than either testing method alone (83% and 84%, respectively). These accuracy data were confirmed by these Belgian results.

Relative sensitivities and specificities were not significantly different from unity in our study, nor in the meta-analysis of Prigge et al. [46], where significance was only reached for the relative specificity of the combination of HPV DNA PCR and p16(INK4a) tests versus p16(INK4a)IHC [rel. spec.: 1.13 (95% CI 1.04–1.23)], by pooling from multiple studies.

Furthermore, better clinical outcomes have been reported for patients with HPV-induced compared to HPV-unrelated OPC [6,7,8,9,10,11]. HPV-positive OPC patients show better age-standardised survival than HPV-negative counterparts, leading to investigation of de-intensified therapies to improve their quality of life. However, recent trials have shown worse survival outcomes [47,48,49]. Therefore, it is crucial to further characterize the molecular mechanisms defining HPV-driven OPC in order to identify novel prognostic markers and, in a more distant future, probable targets for more tailored and effective therapies for this subtype of OPC patients, with a therapeutic success at least equal or improved compared to current treatment regimens.

Improved prognostication by combined p16(INK4a) and hrHPV DNA detection compared to single marker analysis has been demonstrated in a large meta-analysis on tumours in the head and neck region [50]. In our study, 97% (92/95) of the patients would have been correctly diagnosed with the combined testing approach. However, one 58-year old male (current smoker and alcohol consumer) with a T1 (N0 M0) microinvasive tonsillar tumour might have been considered spuriously as having a bad prognosis by applying this combined test strategy, as his tumour would have been classified as a HPV-unrelated case, being p16(INK4a) negative while actually both DNA and mRNA HPV16 positive. More than six years after diagnosis, the patient was alive without any evidence of disease.

On the other hand, disease-specific survival rates are not improved among HPV DNA-positives where HPV is not the cause of carcinogenesis. In our series of 95 Belgian OPC patients, the number of false positive cancers would be reduced from five to two with the combined p16 + DNA detection. The two HPV-unrelated cancer patients were male and diagnosed with a tonsillar cancer. The first patient, with a Tx N2 M1 tonsil NOS tumour, was a heavy drinker and current smoker who only underwent surgery and had a recurrence within 6 months. He died 2 years after being diagnosed. The other patient, with a T3 N2 tonsil NOS tumour, received surgery followed by radiotherapy and concurrent chemotherapy for 2 months. At the last follow-up date, this patient was alive, but with evidence of residual disease. Of note, these two HPV-unrelated patients clearly had a much worse disease status at diagnosis and thereby reduced survival chances compared to the above described HPV-driven tonsillar cancer patient.

Ninety-seven percent of the OPC patients in our study would have been correctly diagnosed as patients with a HPV-driven cancer by combined p16(INK4a) and hrHPV DNA (p16 + DNA) detection. Sequential testing algorithms (p16 → DNA and DNA → p16) resulted in equally accurate results, however, with a 60% reduction in the number of tests needed to be performed. This will cause a substantial reduction in costs and laboratory time, while providing the same clinical value. Especially the algorithm of p16(INK4a) on all samples followed by HPV DNA PCR on p16(INK4a)-positive samples only would be a practical strategy. After all, p16(INK4a) IHC can easily be combined with standard histology when a H&E-stained tissue section is prepared for examination by a pathologist. It is a routine diagnostic procedure, at a relatively low cost, available as a validated in-vitro diagnostic reagent and a fully automated protocol, which generates results within several hours after the procedure has been requested. HPV DNA PCR is also a standard laboratory procedure with high throughput and quick results, although against a higher cost. Preselection by p16(INK4a)-staining therefore reduces the workload and associated costs, and the combination of HPV DNA and p16(INK4a)testing leads to an important reduction of the number of false-positive observations versus the use of either of these assays alone.

Limitations

The limited number of OPC cases and the respective anatomical subsites present in this cohort could have influenced the precision of the accuracy. However, more studies will emerge from the HPV-AHEAD consortium and a new updated meta-analysis on diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas is planned (which will include all studies from the meta-analysis by Prigge et al. [46], several HPV-AHEAD datasets and studies identified from the literature published after the meta-analysis of Prigge). A fine anatomical sub-classification can be incorporated as covariate, which hopefully yields statistical power.

Conclusions

In conclusion, combined testing for hrHPV DNA and p16(INK4a) enhances specificity up to 97%, while maintaining high sensitivity (96%), compared to single testing. The diagnostic test combination represents an accurate and accessible testing strategy in the clinical setting for diagnosis of HPV-induced OPC (especially for base of tongue and tonsillar cancers), allowing discriminant prognostication.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CI:

Confidence intervalFFPE:

Formalin-fixed, paraffin-embeddedH&E:

Hematoxylin and eosinHNC:

Head and neck cancersHPV:

Human papillomavirushrHPV:

High-risk human papillomavirusIHC:

ImmunohistochemistryOPC:

Oropharyngeal cancerp16:

p16(INK4a)PCR:

Polymerase chain reactionRNA+:

mRNA-positiveS:

SectionubC:

Ubiquitin C

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Acknowledgements

We are very grateful for the excellent work performed by Sofie Thys (University of Antwerp, Laboratory of cell biology and histology), for her meticulous work in preparing FFPE slide sections and logistical coordination and support of the study. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.

‘HPV-AHEAD study group’: Christine Carreira3, Sandrine McKay-Chopin3, Rudrapatna S. Jayshree12, Kortikere S. Sabitha12, Ashok M. Shenoy12, Alfredo Zito14, Fausto Chiesa15, Marta Tagliabue15, Mohssen Ansarin15, Subha Sankaran17, Christel Herold-Mende21,22, Gerhard Dyckhoff22, George Mosialos23, Heiner Boeing24, Xavier Castellsagué25†, Silvia de Sanjosé25, Marisa Mena25, Francesc Xavier Bosch25, Laia Alemany25, Pulikottil Okkuru Esmy26, Manavalan Vijayakumar27, Aruna S. Chiwate28, Ranjit V. Thorat28, Girish G. Hublikar28, Shashikant S. Lakshetti28, Bhagwan M. Nene28, Amal Ch Kataki29, Ashok Kumar Das29, Kunnambath Ramadas30, Thara Somanathan30

3Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer (IARC); Lyon; France; 12Kidwai Memorial Institute of Oncology; Bangalore, Karnataka; India; 14IRCCS Istituto Tumori “Giovanni Paolo II”; Bari; Italy; 15Division of Pathology, IEO, European Institute of Oncology IRCCS; Milan; Italy; 17Rajiv Gandhi Centre for Biotechnology; Poojappura, Thiruvananthapuram, Kerala; India; 21Department of Neurosurgery, Head and Neck Surgery, University of Heidelberg; Germany; 22Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg; Germany; 23Aristotle University of Thessaloniki; Greece; 24German Institute of Human Nutrition; Berlin; Germany; 25Catalan Institute of Oncology, IDIBELL, L’Hospitalet de Llobregat; Spain; 26Christian Fellowship Community Health Centre; Ambillikai; India; 27YEN ONCO Centre, Yenepoya University, Deralakatte, Mangalore 575018: Karnataka; India; 28Nargis Dutt Memorial Cancer Hospital; Barshi; India; 29Dr B. Borooah Cancer Institute, Guwahati; Assam; India; 30Regional Cancer Centre; Thiruvananthapuram; India. Dr. Castellsagué passed away on June 12th, 2016.

Funding

The global HPV-AHEAD study was initially funded by the European Commission, with Grant Number: FP7-HEALTH-2011-282562. Sciensano, the employer of CS and MA, received funding for the analysis of the Belgian part of the HPV-AHEAD study, in part, by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. MA was also supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (Grant No. 847845); and the Belgian Foundation Against Cancer through the IHUVACC project.

Author information

Authors and Affiliations

  1. Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Juliette Wytsmanstraat 14, 1050, Brussels, BelgiumCindy Simoens & Marc Arbyn
  2. AMBIOR, Laboratory for Cell Biology & Histology, University of Antwerp, Antwerp, BelgiumCindy Simoens, Ivana Gorbaslieva & Johannes Bogers
  3. Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer (IARC), Lyon, FranceTarik Gheit, Eric Lucas, Massimo Tommasino, Christine Carreira & Sandrine McKay-Chopin
  4. Roche Diagnostics GmbH, Mannheim, GermanyRuediger Ridder & Susanne Rehm
  5. Ventana Medical Systems, Inc. (Roche Diagnostics Solutions), Tucson, AZ, USARuediger Ridder
  6. Infections and Cancer Epidemiology, Research Program Infection, Inflammation and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, GermanyDana Holzinger & Michael Pawlita
  7. Laboratory for Pathological Anatomy, Sint Augustinus Hospital, GZA, Antwerp, BelgiumPeter Vermeulen
  8. Department of Pathology, Antwerp University Hospital, Edegem, BelgiumMartin Lammens
  9. Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumMartin Lammens
  10. Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, BelgiumOlivier M. Vanderveken
  11. Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumOlivier M. Vanderveken
  12. Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, 560029, IndiaRekha Vijay Kumar
  13. Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra State, 442102, IndiaNitin Gangane
  14. IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, ItalyAlessandro Caniglia
  15. Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, ItalyFausto Maffini
  16. Hospital del Mar, Parc de Salut Mar, Pg/Marítim 25-29, 08003, Barcelona, SpainMaria Belén Lloveras Rubio
  17. Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, 695014, IndiaDevasena Anantharaman & Madhavan Radhakrishna Pillai
  18. Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, ItalySusanna Chiocca
  19. Genomic Epidemiology Branch, International Agency for Research On Cancer (IARC), Lyon, FrancePaul Brennan
  20. Research Triangle Institute (RTI) International India, New Delhi, IndiaRengaswamy Sankaranarayanan

Consortia

the HPV-AHEAD study group

  • Christine Carreira
  • , Sandrine McKay-Chopin
  • , Rudrapatna S. Jayshree
  • , Kortikere S. Sabitha
  • , Ashok M. Shenoy
  • , Alfredo Zito
  • , Fausto Chiesa
  • , Marta Tagliabue
  • , Mohssen Ansarin
  • , Subha Sankaran
  • , Christel Herold-Mende
  • , Gerhard Dyckhoff
  • , George Mosialos
  • , Heiner Boeing
  • , Xavier Castellsagué
  • , Silvia de Sanjosé
  • , Marisa Mena
  • , Francesc Xavier Bosch
  • , Laia Alemany
  • , Pulikottil Okkuru Esmy
  • , Manavalan Vijayakumar
  • , Aruna S. Chiwate
  • , Ranjit V. Thorat
  • , Girish G. Hublikar
  • , Shashikant S. Lakshetti
  • , Bhagwan M. Nene
  • , Amal Ch. Kataki
  • , Ashok Kumar Das
  • , Kunnambath Ramadas
  •  & Thara Somanathan

Contributions

CS, MA and JB designed the Belgian part of the HPV-AHEAD study; CS and MA performed the statistical analysis and interpreted the findings; CS also compiled the database, managed the Belgian part of the project and wrote the manuscript. IG collected all patient samples and the corresponding clinical information; PV, ML and OMV facilitated and supervised the specimen and clinical data collection. TG, DH, SR, AC, DA, and PB performed the respective DNA, RNA or p16 tests, and interpreted the data; they were supervised by MT, MP, RR, and MRP. RVK, NG, FM, BMLR, and JB were responsible for the histological review of all specimens. EL managed the overall HPV-AHEAD database, and validated the data entry. MT, RS, MP, MA, JB, SC, and RR were the PI’s of the HPV-AHEAD study and therefore responsible for the largest funding acquisition. TG, RR, IG, EL, FM, SC, JB, MT, and MA reviewed and/or edited the manuscript. All co-authors approved the final manuscript and its submission to this journal.

Corresponding authors

Correspondence to Cindy Simoens or Marc Arbyn.

Ethics declarations

Ethics approval and consent to participate

All methods were carried out in accordance with relevant guidelines and regulations. Ethical clearance was obtained from the Ethical Committees of ‘GZA hospitals’ (ref nb: BVDE/hp/2013/01.147), ‘UZA & UA (University of Antwerp)’ (ref nb: 11/47/362) and IARC, Lyon, France (ref nb: 11–30). Informed consent of the individual patient was not necessary, as it concerns biobank-based research. The ethical principles, detailed by a European network specialized in biobanking (Hansson MG, Methods Mol.Biol 2011; 675:39–59), are respected. The need of informed consent was waived by the Ethical Committees of ‘GZA hospitals’ and ‘UZA & UA (University of Antwerp)’ for the Belgian patients.

Consent for publication

Not applicable.

Competing interests

RR and SR are employees of Roche. All other authors declare that they have no competing interests.

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NFL Hall of Fame QB and Oral Cancer

Jim Kelly’s health remains good after beating cancer

Bills Hall of Fame quarterback had a long battle with oral cancer that gave him a bleak prognosis and required multiple surgeries on his jaw, radiation and chemotherapy. But more than three years after announcing that the cancer was gone, Kelly says there’s been no recurrence and his health is now good.

While hosting his football camp in Buffalo and throwing passes to kids, Kelly spoke with his speech only mildly affected, and said he’s healthy.

Backstory

Original Article: March 6, 2018

Jim Kelly, the NFL Hall of Fame quarterback and former University of Miami football standout, announced Thursday that he will once again undergo treatment for oral cancer after recent testing indicated the cancer has returned.

Mr. Kelly, 58, was diagnosed with squamous cell carcinoma in his upper jaw in June 2013. At that time, doctors at Erie County Medical Center in Buffalo, N.Y., removed part of his upper jaw, part of the roof of his mouth and numerous teeth. He got a prosthesis to replace the teeth and bone that was removed during his surgery. Mr. Kelly, who graduated from UM in 1983, played for 11 seasons with the Buffalo Bills, leading the team to four Super Bowls.

Cancers of the oral cavity may involve bone, teeth, muscle, nerves, blood vessels, saliva glands and the inside lining of the lips and cheeks. The most common cancer of the oral cavity is squamous cell carcinoma, and it arises from the lining of the inside the mouth, the nose and the throat, according to the National Cancer Institute.

‘This can Happen to Anyone at Any Age’
“There’s a small percentage who have never smoked or drank alcohol who get cancer of the oral cavity,” says Geoffrey Young, M.D., Ph.D., FACS, chief of head and neck surgery at Miami Cancer Institute, who treats patients diagnosed with oral cancer but was not involved in Mr. Kelly’s case. “This can happen to anyone at any age so it’s always a good idea to get a yearly oral cancer screening from your dentist or primary care physician. Prevention is always better.”

Tobacco use and excessive alcohol are the main risk factors for this type of oral cancer. Mr. Kelly has said he never smoked cigarettes or chewed tobacco but smoked cigars occasionally. A small percentage of people (under 7 percent) get oral cancers from no identified cause, says the Oral Cancer Foundation. It is believed that these are likely related to some genetic predisposition, the Foundation says.

Dentists usually screen patients for oral cancer before performing regular cleanings or other procedures.  A primary care physician can also examine the oral cavity for sores or unusual growths. Before his initial diagnosis in 2013, Mr. Kelly said he suffered from pain in his jaw.

“If you have any sore or growth in the mouth that doesn’t heal within 30 days, then you should get it checked out by your dentist or primary care doctor,” Dr. Young said. “Initially, these sores may not even be painful.”

Mr. Kelly’s cancer has returned for the second time. Nine months after his first surgery in March 2014, Mr. Kelly announced the cancer had returned and aggressively spread to his brain, sinus cavity and adjacent tissues. He underwent months of treatment — including chemotherapy — that removed the cancerous cells. Before Thursday’s announcement, he had been believed to be free of cancer since September 2014. Since then, Mr. Kelly has taken part in Oral, Head & Neck Cancer Awareness campaigns, urging Americans to get screened.

Oral cancer is the largest group of the cancers that fall under the head and neck cancer category. Approximately 51,500 people in the U.S. will be newly diagnosed with oral cancer in 2018, projects the Oral Cancer Foundation. The foundation estimates that almost 10,000 people die from oral cancers every year, although not all of these cases are specifically cancers of the oral cavity.

The oral cavity includes the lips, the inside lining of the lips and cheeks (buccal mucosa), the teeth, the gums, the front two-thirds of the tongue, the floor of the mouth below the tongue and the bony roof of the mouth (hard palate). Oropharyngeal cancer starts in the oropharynx, which is the part of the throat just behind the mouth.

The human papillomavirus (HPV) has emerged in recent years as a possible leading cause of oropharyngeal (tonsil and base of tongue) cancers, particularly in non-smokers and younger age groups. Over half of tonsil and base of tongue cancers are linked to HPV. The U.S. Centers for Disease and Prevention (CDC) says that up to 70 percent of oropharyngeal cancers may be associated with HPV.

In a statement announcing that his cancer had returned, Mr. Kelly stated: “The oral cancer we hoped would be gone forever has returned. Although I was shocked and deeply saddened to receive this news, I know that God is with me. I continuously talk about the four F’s: Faith, Family, Friends and Fans. With all of you by my side, we will fight and win this battle together. Staying ‘Kelly Tough’ and trusting God will carry us through this difficult time.”

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Transmission of HPV does not distinguish between gender

Transmission of HPV does not distinguish between gender, which is why we emphasize vaccination, emphasizes Dra. Ortiz. For the female population there are more options to detect it, but both sexes transmit it. Dr. Alexandra Ortiz Orama, obstetrician-gynecologist at the San Lucas Episcopal Medical Center in Ponce.

During the last decades it has been confirmed that the incidence of the virus is the same in men and women, even though there are no accurate statistics on the percentage of the male population that contracts the virus. However, it is more often diagnosed in sexually active women.

This was indicated by Dr. Alexandra Ortiz Orama, obstetrician gynecologist at the San Lucas Episcopal Medical Center in Ponce, who assured that this Sexually Transmitted Infection (STI) is one of the most common in young people between 20 and 25 years old.

“We are not detecting the virus in men because we don’t have tests to test them; we don’t have a standardized test for them, only for women. So we only realize that it occurs in women, but men have it. just as often as women,” the expert stressed.

In addition to this, the expert mentioned that the prevalence of HPV diagnosis falls mainly on young women between 20 and 25 years old. This is because, in this reproductive stage, the cervix is ​​exposed to the vagina, so it is easier to contract the virus.

“This is why the test should not be performed before the age of 21, because if we perform the HPV test before that age, the vast majority will come out positive and will lead to a series of psychological problems in young women and the urgency resorting to unnecessary treatment,” he said.

More than 200 strains of Human Papillomavirus have been identified, however, experts highlight the potential risk of strains 16, 18, 6 and 11 as they are closely related to the development of cervical cancer, vaginal cancer, anal cancer and cancer oral.

“HPV is one of the most common infections in, say, the United States. About 20 million people get it every year, and it’s said that 4 women out of 5 are going to get it at some point in their lives.” , emphasized the expert.

HPV detection: Does not produce symptoms in the initial stage

Diagnosis is usually made as routine procedure that is part of the consultation protocol when women go for gynecological examinations, such as the PAP. Unfortunately, this is the only way to be able to detect the presence of the virus, since there are no blood tests and, therefore, it is only detectable in women.

“People who have it don’t know they have it, and it is detected thanks to common test results. Now, when women have symptoms, such as bleeding and/or pain during sexual intercourse, bloody vaginal discharge, among others, may already be signs that the patient is in stage of pre-cancer or cancer of the cervix, caused by HPV,” said Dr. Ortiz.

Once women are diagnosed with HPV, they receive clinical follow-up to identify the behavior of the virus in the patient’s body, and the damage it is doing to the body, if the infection it carries contains the most dangerous strains, among others.

Hence the importance of following the medical recommendations to regularly visit the gynecologist, strengthen the immune system because, in fact, most women can eliminate this virus on their own: “Really, this virus can be eliminated in about 2 years, That is why good health, exercise, nutrition and good sexual practice are important to combat it”.

In addition, it is also pertinent to remember that this virus is highly transmissible and does not necessarily spread through vaginal penetration, but by skin-to-skin contactoral, vaginal or anal intercourse.

HPV prevention campaigns

We must remember that, so far, there is no drug that can completely eliminate the virus. However, if the woman presents alterations in the cancer tests, she can undergo a colposcopy to, again, detail the percentage of damage she has caused in the body. If the virus has already exacerbated to a pre-cancerous stage, the patient may receive treatment such as cryosurgery and removal of the affected area.

The other treatments have a more preventive approach so that the woman tries to eliminate the virus, and prevent it from reaching highly risky stages for her health.

Over the years, vaccination has been improving, although the expert acknowledges that there is still much to be done: “First we had a vaccine against two strains, the second attacked four, and currently the vaccine we have combats 9 high-risk strains “.

Recently, medicine and, above all, the specialty of gynecology celebrated an important milestone in the fight against this virus, which was the expansion of the target group for prevention and immunity that would receive the vaccines, since from 26 years of age, it was expanded to 45 .

“The best age to be vaccinated is 12 years old, before the person is sexually active, because once there is sexual activity, the probability that the person is in contact with the virus is very high,” the specialist confessed.

Constant studies on the subject have proven that the vaccine is highly safe and effective, so there should be no fear regarding its application. In fact, the secondary effects of the vaccine are not serious at all, and neither does it alter health or leave negative effects.

“The receptivity of the vaccines has been good, everyone wants to be vaccinated. There are limitations between medical plans, since it is approved until the age of 45, but the coverage is until the age of 26. After that age, only some specific plans cover it , since the probability that the person is sexually active after the age of 26 is high,” he explained. “If, for example, someone has strain 16, which is the most dangerous, you will have coverage against the other strains. It is also important that patients know that, even if they have the virus, they should be vaccinated.”

General recommendations of the expert for the prevention of HPV

“The most valuable thing is to visit the doctor to do routine tests. We women have some very considerable tests that we must carry out annually, especially mammography after 40. In addition, we must take care of our diet, exercise 3 or 4 times a a week, take vitamin and folic acid in reproductive age, which helps to avoid congenital defects if we become pregnant, such as spina bifida. These are preventive habits that we must follow,” she concluded.

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Transmission of HPV does not distinguish between gender

Transmission of HPV does not distinguish between gender, which is why we emphasize vaccination, emphasizes Dra. Ortiz. For the female population there are more options to detect it, but both sexes transmit it. Dr. Alexandra Ortiz Orama, obstetrician-gynecologist at the San Lucas Episcopal Medical Center in Ponce.

During the last decades it has been confirmed that the incidence of the virus is the same in men and women, even though there are no accurate statistics on the percentage of the male population that contracts the virus. However, it is more often diagnosed in sexually active women.

This was indicated by Dr. Alexandra Ortiz Orama, obstetrician gynecologist at the San Lucas Episcopal Medical Center in Ponce, who assured that this Sexually Transmitted Infection (STI) is one of the most common in young people between 20 and 25 years old.

“We are not detecting the virus in men because we don’t have tests to test them; we don’t have a standardized test for them, only for women. So we only realize that it occurs in women, but men have it. just as often as women,” the expert stressed.

In addition to this, the expert mentioned that the prevalence of HPV diagnosis falls mainly on young women between 20 and 25 years old. This is because, in this reproductive stage, the cervix is ​​exposed to the vagina, so it is easier to contract the virus.

“This is why the test should not be performed before the age of 21, because if we perform the HPV test before that age, the vast majority will come out positive and will lead to a series of psychological problems in young women and the urgency resorting to unnecessary treatment,” he said.

More than 200 strains of Human Papillomavirus have been identified, however, experts highlight the potential risk of strains 16, 18, 6 and 11 as they are closely related to the development of cervical cancer, vaginal cancer, anal cancer and cancer oral.

“HPV is one of the most common infections in, say, the United States. About 20 million people get it every year, and it’s said that 4 women out of 5 are going to get it at some point in their lives.” , emphasized the expert.

HPV detection: Does not produce symptoms in the initial stage

Diagnosis is usually made as routine procedure that is part of the consultation protocol when women go for gynecological examinations, such as the PAP. Unfortunately, this is the only way to be able to detect the presence of the virus, since there are no blood tests and, therefore, it is only detectable in women.

“People who have it don’t know they have it, and it is detected thanks to common test results. Now, when women have symptoms, such as bleeding and/or pain during sexual intercourse, bloody vaginal discharge, among others, may already be signs that the patient is in stage of pre-cancer or cancer of the cervix, caused by HPV,” said Dr. Ortiz.

Once women are diagnosed with HPV, they receive clinical follow-up to identify the behavior of the virus in the patient’s body, and the damage it is doing to the body, if the infection it carries contains the most dangerous strains, among others.

Hence the importance of following the medical recommendations to regularly visit the gynecologist, strengthen the immune system because, in fact, most women can eliminate this virus on their own: “Really, this virus can be eliminated in about 2 years, That is why good health, exercise, nutrition and good sexual practice are important to combat it”.

In addition, it is also pertinent to remember that this virus is highly transmissible and does not necessarily spread through vaginal penetration, but by skin-to-skin contactoral, vaginal or anal intercourse.

HPV prevention campaigns

We must remember that, so far, there is no drug that can completely eliminate the virus. However, if the woman presents alterations in the cancer tests, she can undergo a colposcopy to, again, detail the percentage of damage she has caused in the body. If the virus has already exacerbated to a pre-cancerous stage, the patient may receive treatment such as cryosurgery and removal of the affected area.

The other treatments have a more preventive approach so that the woman tries to eliminate the virus, and prevent it from reaching highly risky stages for her health.

Over the years, vaccination has been improving, although the expert acknowledges that there is still much to be done: “First we had a vaccine against two strains, the second attacked four, and currently the vaccine we have combats 9 high-risk strains “.

Recently, medicine and, above all, the specialty of gynecology celebrated an important milestone in the fight against this virus, which was the expansion of the target group for prevention and immunity that would receive the vaccines, since from 26 years of age, it was expanded to 45 .

“The best age to be vaccinated is 12 years old, before the person is sexually active, because once there is sexual activity, the probability that the person is in contact with the virus is very high,” the specialist confessed.

Constant studies on the subject have proven that the vaccine is highly safe and effective, so there should be no fear regarding its application. In fact, the secondary effects of the vaccine are not serious at all, and neither does it alter health or leave negative effects.

“The receptivity of the vaccines has been good, everyone wants to be vaccinated. There are limitations between medical plans, since it is approved until the age of 45, but the coverage is until the age of 26. After that age, only some specific plans cover it , since the probability that the person is sexually active after the age of 26 is high,” he explained. “If, for example, someone has strain 16, which is the most dangerous, you will have coverage against the other strains. It is also important that patients know that, even if they have the virus, they should be vaccinated.”

General recommendations of the expert for the prevention of HPV

“The most valuable thing is to visit the doctor to do routine tests. We women have some very considerable tests that we must carry out annually, especially mammography after 40. In addition, we must take care of our diet, exercise 3 or 4 times a a week, take vitamin and folic acid in reproductive age, which helps to avoid congenital defects if we become pregnant, such as spina bifida. These are preventive habits that we must follow,” she concluded.

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Prevent Cervical Cancer & HPV

There is no guaranteed way to prevent cervical cancer. However, by getting the human papillomavirus (HPV) vaccine, if possible, and undergoing regular testing, a person can significantly reduce their risk. Using barrier methods of protection during sexual activity, avoiding smoking, and making certain dietary changes may also be beneficial.

Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.

The American Cancer Society (ACS) estimates that in 2022, approximately 4,280 femalesTrusted Source will die from cervical cancer in the United States.

Although it is not always possible to prevent cervical cancer, the ACSTrusted Source notes that getting regular tests and receiving the HPV vaccine are the most important steps a person can take to avoid this disease developing.

Testing can allow doctors to identify precancerous changes and provide early treatment. The vaccine helps prevent infection with HPV, which is a virus that can lead to cervical cancer.

This article looks in more detail at what a person can do to help minimize  and prevent the risk of cervical cancer.

Screening for cervical cancer

A person talking to a healthcare professional about how to prevent cervical cancer.

The ACSTrusted Source advises that the best way to ensure that doctors find cervical cancer early is to undergo regular screening tests. A doctor can do an HPV test or a Pap test. Alternatively, they can do both together, which they will refer to as a co-test. People aged 25–65 yearsTrusted Source with a cervix should request an HPV test from a doctor every 5 years or a Pap test every 3 years. Doctors can perform both of these tests at their clinic or office. A person should receive the result within 3 weeksTrusted Source.

HPV test

According to the World Health Organization (WHO), HPV is associated with 99%Trusted Source of cervical cancer cases. HPV is an extremely common virus that people can contract through sexual contact. It is important to note that nearly all sexually active people contract HPV and that most casesTrusted Source do not lead to cancer. The immune system usually controls the HPV infection. An HPV test can reveal cell changes that may lead to cervical cancer. This gives doctors a chance to treat the cells before they develop further.

PAP test

People sometimes refer to this test as a PAP smear. The test looks for precancerous changes in the cells in the cervix. These cells could become cancerous without treatment. A healthcare professional will use an instrument called a speculum to widen the vagina and then use a swab to collect a sample from the cervix. They will send the cells to a laboratory for analysis.

How to get a cervical screening to prevent HPV

A person can contact their local doctor’s office to inquire about cervical screening. Alternatively, they can make an appointment with Planned Parenthood here. The Centers for Disease Control and Development (CDC)Trusted Source note that those with a low income or without insurance may qualify for free or low cost screening tests through its National Breast and Cervical Cancer Early Detection Program (NBCCEDP).

The CDCTrusted Source advises that, alongside screening, getting an HPV vaccine is the most important thing someone can do to prevent cervical cancer.

The HPV vaccine protects against the types of HPV that most often cause cervical, vaginal, and vulvar cancers.

Preteens aged 11–12 years and everyone under the age of 26 years should get the HPV vaccine. People may need two or three doses, depending on their age.

Although doctors do not typically recommend the vaccine for those older than 26 years, some people aged 27–45 years may choose to get the vaccine after consulting a doctor.

Some people may have heard reports about safety concerns relating to the Gardasil vaccine. However, the Food and Drug Administration (FDA)Trusted Source has concluded that the vaccine is safe and that its benefits outweigh any risks.

Learn more about the HPV vaccine.

How to get the vaccine

A person can get the HPV vaccine at their local clinic, health department, or Planned Parenthood health center.

According to Planned Parenthood, the average cost of a single dose is $250. However, many health insurance companies will cover the cost of the HPV vaccine for those who are eligible.

A person without insurance can ask a doctor or nurse for information on how to get the HPV vaccine at a lower cost.

The federally funded Vaccines for Children (VFC)Trusted Source program covers vaccine costs for children and teenagers who have no insurance or insufficient insurance.

Using barrier protection methods during sexual activity

The HPV infection spreads through sexual contact.

According to the National Cancer InstituteTrusted Source, the risk of HPV infection is higher in females who became sexually active before the age of 18 years and in those who have had six or more sexual partners.

Using a barrier method of birth control, such as a condom or dental dam, helps protect against HPV infection.

However, it is important to note that a person can still getTrusted Source HPV from the areas that the condom or dental dam does not cover, such as the genital skin or the area around the anus.

Avoiding smoking

The CDCTrusted Source explains that smoking can cause different types of cancer, including cervical cancer.

Toxic substances in tobacco smoke can weaken the immune system, making it harder for the body to kill cancer cells. Additionally, these poisons can damage or change the cell’s DNA, causing a tumor to start developing. Avoding smoking will help prevent HPV

2019 studyTrusted Source also found that passive smoking and having a sexual partner who smokes may contribute to cervical cancer risk.

Nicotine and other substances in tobacco may pass to the cervix through semen, compromising the immune system and the body’s ability to defend itself against cancer.

Diet

The author of a 2019 reviewTrusted Source examined the dietary components that may protect against HPV and cervical cancer. They noted that the following can help protect against HPV infection:

  • antioxidants, such as vitamins A, C, and E, in fruits and vegetables
  • polyphenols, flavonoids, lycopene, and sulforaphane in plant foods and teas
  • folate, calcium, and vitamin D
  • nuts and legumes

Another studyTrusted Source in China found that a low intake of certain nutrients — folate, niacin, and vitamins B6, C, and K — was associated with a higher risk of cervical intraepithelial neoplasia (CIN).

CIN2 cells are moderatelyTrusted Source abnormal cells that are present on the surface of the cervix. These cells are not yet cancerous, but they can become cancerous.

In addition, research suggests that people should avoid:

Higher glycemic index (GI) foods

Research from 2020Trusted Source notes that the consumption of low GI foods can play a role in preventing cervical cancer.

Experts advise that regular screening may help prevent cervical cancer from developing or detect it in its early stages.

In addition, getting an HPV vaccine can protect people from contracting this common virus through sexual contact. HPV can lead to cervical cancer.

People can lower their risk of developing cervical cancer by using barrier protection methods during sexual activity and avoiding smoking.

Furthermore, eating a well-balanced, nutrient-dense diet can provide antioxidants to help the immune system protect against HPV.

Original Article

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READ MORE

Prevent Cervical Cancer & HPV

There is no guaranteed way to prevent cervical cancer. However, by getting the human papillomavirus (HPV) vaccine, if possible, and undergoing regular testing, a person can significantly reduce their risk. Using barrier methods of protection during sexual activity, avoiding smoking, and making certain dietary changes may also be beneficial.

Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.

The American Cancer Society (ACS) estimates that in 2022, approximately 4,280 femalesTrusted Source will die from cervical cancer in the United States.

Although it is not always possible to prevent cervical cancer, the ACSTrusted Source notes that getting regular tests and receiving the HPV vaccine are the most important steps a person can take to avoid this disease developing.

Testing can allow doctors to identify precancerous changes and provide early treatment. The vaccine helps prevent infection with HPV, which is a virus that can lead to cervical cancer.

This article looks in more detail at what a person can do to help minimize  and prevent the risk of cervical cancer.

Screening for cervical cancer

A person talking to a healthcare professional about how to prevent cervical cancer.

The ACSTrusted Source advises that the best way to ensure that doctors find cervical cancer early is to undergo regular screening tests. A doctor can do an HPV test or a Pap test. Alternatively, they can do both together, which they will refer to as a co-test. People aged 25–65 yearsTrusted Source with a cervix should request an HPV test from a doctor every 5 years or a Pap test every 3 years. Doctors can perform both of these tests at their clinic or office. A person should receive the result within 3 weeksTrusted Source.

HPV test

According to the World Health Organization (WHO), HPV is associated with 99%Trusted Source of cervical cancer cases. HPV is an extremely common virus that people can contract through sexual contact. It is important to note that nearly all sexually active people contract HPV and that most casesTrusted Source do not lead to cancer. The immune system usually controls the HPV infection. An HPV test can reveal cell changes that may lead to cervical cancer. This gives doctors a chance to treat the cells before they develop further.

PAP test

People sometimes refer to this test as a PAP smear. The test looks for precancerous changes in the cells in the cervix. These cells could become cancerous without treatment. A healthcare professional will use an instrument called a speculum to widen the vagina and then use a swab to collect a sample from the cervix. They will send the cells to a laboratory for analysis.

How to get a cervical screening to prevent HPV

A person can contact their local doctor’s office to inquire about cervical screening. Alternatively, they can make an appointment with Planned Parenthood here. The Centers for Disease Control and Development (CDC)Trusted Source note that those with a low income or without insurance may qualify for free or low cost screening tests through its National Breast and Cervical Cancer Early Detection Program (NBCCEDP).

The CDCTrusted Source advises that, alongside screening, getting an HPV vaccine is the most important thing someone can do to prevent cervical cancer.

The HPV vaccine protects against the types of HPV that most often cause cervical, vaginal, and vulvar cancers.

Preteens aged 11–12 years and everyone under the age of 26 years should get the HPV vaccine. People may need two or three doses, depending on their age.

Although doctors do not typically recommend the vaccine for those older than 26 years, some people aged 27–45 years may choose to get the vaccine after consulting a doctor.

Some people may have heard reports about safety concerns relating to the Gardasil vaccine. However, the Food and Drug Administration (FDA)Trusted Source has concluded that the vaccine is safe and that its benefits outweigh any risks.

Learn more about the HPV vaccine.

How to get the vaccine

A person can get the HPV vaccine at their local clinic, health department, or Planned Parenthood health center.

According to Planned Parenthood, the average cost of a single dose is $250. However, many health insurance companies will cover the cost of the HPV vaccine for those who are eligible.

A person without insurance can ask a doctor or nurse for information on how to get the HPV vaccine at a lower cost.

The federally funded Vaccines for Children (VFC)Trusted Source program covers vaccine costs for children and teenagers who have no insurance or insufficient insurance.

Using barrier protection methods during sexual activity

The HPV infection spreads through sexual contact.

According to the National Cancer InstituteTrusted Source, the risk of HPV infection is higher in females who became sexually active before the age of 18 years and in those who have had six or more sexual partners.

Using a barrier method of birth control, such as a condom or dental dam, helps protect against HPV infection.

However, it is important to note that a person can still getTrusted Source HPV from the areas that the condom or dental dam does not cover, such as the genital skin or the area around the anus.

Avoiding smoking

The CDCTrusted Source explains that smoking can cause different types of cancer, including cervical cancer.

Toxic substances in tobacco smoke can weaken the immune system, making it harder for the body to kill cancer cells. Additionally, these poisons can damage or change the cell’s DNA, causing a tumor to start developing. Avoding smoking will help prevent HPV

2019 studyTrusted Source also found that passive smoking and having a sexual partner who smokes may contribute to cervical cancer risk.

Nicotine and other substances in tobacco may pass to the cervix through semen, compromising the immune system and the body’s ability to defend itself against cancer.

Diet

The author of a 2019 reviewTrusted Source examined the dietary components that may protect against HPV and cervical cancer. They noted that the following can help protect against HPV infection:

  • antioxidants, such as vitamins A, C, and E, in fruits and vegetables
  • polyphenols, flavonoids, lycopene, and sulforaphane in plant foods and teas
  • folate, calcium, and vitamin D
  • nuts and legumes

Another studyTrusted Source in China found that a low intake of certain nutrients — folate, niacin, and vitamins B6, C, and K — was associated with a higher risk of cervical intraepithelial neoplasia (CIN).

CIN2 cells are moderatelyTrusted Source abnormal cells that are present on the surface of the cervix. These cells are not yet cancerous, but they can become cancerous.

In addition, research suggests that people should avoid:

Higher glycemic index (GI) foods

Research from 2020Trusted Source notes that the consumption of low GI foods can play a role in preventing cervical cancer.

Experts advise that regular screening may help prevent cervical cancer from developing or detect it in its early stages.

In addition, getting an HPV vaccine can protect people from contracting this common virus through sexual contact. HPV can lead to cervical cancer.

People can lower their risk of developing cervical cancer by using barrier protection methods during sexual activity and avoiding smoking.

Furthermore, eating a well-balanced, nutrient-dense diet can provide antioxidants to help the immune system protect against HPV.

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